Comparing real-world Type 2 diabetes management with the Francophone Diabetes Society’s recommendations:  using comprehensive geriatric assessment-guided medication reviews of frail older adults living with comorbid diabetes and cancer

Comparing real-world Type 2 diabetes management with the Francophone Diabetes Society’s recommendations: using comprehensive geriatric assessment-guided medication reviews of frail older adults living with comorbid diabetes and cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparing real-world Type 2 diabetes management with the Francophone Diabetes Society’s recommendations: using comprehensive geriatric assessment-guided medication reviews of frail older adults living with comorbid diabetes and cancer Clémence Guerra, Florian Correard, Coline Montegut, Jérémie Nakache, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5349587/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose : Substantial clinical heterogeneity in older adults with diabetes makes therapeutic management challenging. This study compared real-world type 2 diabetes management of older outpatients who had comorbid cancer with published guidelines in order to identify the circumstances in which antidiabetic treatment de-intensification might be appropriate. Methods : We retrospectively analysed data from comprehensive geriatric assessment-guided medication reviews of all outpatients with comorbid diabetes referred to our geriatric oncology day hospital unit in 2022-2023. Results : Of the 738 outpatients who had a medication review, 190 had comorbid diabetes; mean age was 79.5 ± 5.6 years. Despite the high prevalence of frailties and geriatric syndromes observed, the mean HbA1c level was low (6.89% ± 1.03%). Two-thirds (63.5%) of participants had an HbA1c outside the recommended individual target range. Of these, 80% had an HbA1c below the range, suggesting overtreatment. Sulfonylureas and glinides accounted for 18.4% and 11.6% of antidiabetic prescriptions, respectively. A total of 170 diabetes-related therapeutic issues were identified in 67.9% of patients. Having an HbA1c below the individual target range ( p < 0.001) and receiving at least three prescribed antidiabetic drugs ( p < 0.05) were both significantly associated with having at least one diabetes-related therapeutic issue. Conclusion : Our study revealed overly aggressive glycaemic control in this frail older population of patients with comorbid cancer and diabetes and highlights poor clinical adherence to official guidelines. Geriatrician-pharmacist collaborations could provide a more comprehensive understanding of patients’ health status and functional category profiles and improve the therapeutic management of older patients with diabetes. Diabetes Older cancer adults Geriatrician-pharmacist collaboration Pharmaceutical care Therapeutic management Key summary points Aim: Our aim was to compare the real-world type 2 diabetes management with published guidelines in older outpatients with comorbid cancer, who were referred to our geriatric oncology day hospital for a comprehensive geriatric assessment-guided medication review. Findings: Most patients had overly aggressive glycaemic control and were overtreated. Diabetes-related therapeutic issueswere associated with having an actual HbA1c levels below the individual target range and receiving at least three prescribed antidiabetics drugs. Message: These findings highlight the lack of adjustment of therapeutic objectives for type 2 diabetes in older adults and the poor adherence of prescribers to the recommendations. Geriatrician-pharmacist collaboration could guide individual therapeutic choices according to individualised glycaemic targets. Introduction Type 2 diabetes mellitus (T2DM) represents a significant public health issue worldwide; prevalence in older adults is gradually increasing due to population ageing, longer life expectancies, and higher incidence in the general population. It is estimated that almost one-quarter of people with diabetes are aged 70 years or over [ 1 ], and diabetes prevalence among adults aged 75–79 years is projected to reach 25% by 2045 [ 2 ]. Compared to younger adults, older adults present a more heterogeneous profile in terms of diabetes-related complications, comorbidities, associated polypharmacy (defined here as taking at least five prescribed medications per day [ 3 ]) and functional status [ 4 ]. Moreover, the aging process can result in alterations to pharmacokinetic and pharmacodynamic parameters, influencing therapeutic drug responses. In addition, impaired counter-regulatory mechanisms render older adults more vulnerable to adverse effects, particularly hypoglycaemia [ 5 ]. The latter increases the risk of cardiovascular events and mortality [ 6 , 7 ]; accordingly, older people at high risk of falls, malnutrition or neurocognitive decline need to be especially careful. All these factors highlight the challenges clinicians face in providing adequate pharmacological T2DM management to older adults. Advanced age should never be an obstacle to diabetes treatment, but medication prescriptions for older people who are frail or who have multiple comorbidities may need to be adjusted for safety and tolerability reasons. Moreover, deprescribing can avoid unnecessary medication or medication-related harms [ 8 ]. In terms of persons with diabetes, based on results from the French study GERODIAB showing that glycated haemoglobin (HbA1c) thresholds are one of the main factors influencing survival in the older population [ 9 ], the Francophone Diabetes Society (SFD) recommends less stringent glycaemic control for frail and dependent older adults than for the healthy general population, and a more flexible therapeutic approach to managing the disease [ 10 ]. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) also recommend a personalised approach to treatment based on individual characteristics and comorbidities [ 11 ]. Despite this, there is evidence of persistent overtreatment of older adults with T2DM [ 12 ], and insufficient compliance with diabetes guidelines, probably due to therapeutic inertia on the part of prescribers [ 13 ]. Comprehensive geriatric assessment (CGA) is a validated approach in the management of older adults with cancer [ 14 ]. According to the International Society of Geriatric Oncology (SIOG) [ 15 , 16 ], close cooperation between geriatricians and clinical pharmacists during CGAs leads to high-quality medication reviews (MRs) and ensures that adverse side effects of treatments are avoided [ 17 ]. For several years now, our geriatric oncology day hospital unit has performed CGA-guided MRs, as we believe that by taking into account social determinants of health, barriers to care, comorbidities, the level of hyperglycaemia, the risk of medication-related complications, and patient susceptibility to medication-related side effects, more personalized - and therefore more effective - T2DM management can be offered. In the two last years, our CGA-guided MRs have highlighted considerable heterogeneity in the management of T2DM in outpatients with comorbid diabetes who are referred to our unit. High-quality comorbid diabetes control and management is essential in older cancer patients requiring systemic treatment. In this context, the present study aimed to: (i) compare the real-world management of comorbid T2DM in patients who have cancer with published guidelines [ 10 ], (2) provide an overview of the diabetes-related therapeutic issues (DTI) identified and recommendations made in our MRs, and (3) describe the factors associated with having at least one DTI. Material and Methods Study design and population This is a monocentric retrospective observational study. It included all outpatients with comorbid cancer and T2DM referred to the geriatric oncology day unit in the University Hospital of Marseille (AP-HM, France), for a CGA-guided MR between January 2022 and December 2023. French guidelines stipulate that oncologists can only refer patients to the unit prior to initiating systemic oncological treatment, if they have an impaired Geriatric 8 (G8) score (≤ 14 out of 17), or if their G8 score is normal but they have suspected frailties not identified by the G8 scale (e.g., depression or loss of autonomy) [18]. CGAs and MRs are conducted by, respectively, a geriatrician and a clinical pharmacist in our day hospital unit. At the end of each CGA, the geriatrician contacts the patient’s general practitioner (GP) and oncologist to communicate the various medication modifications that the unit has already made or believes should be made (i.e., recommendations). In accordance with French law, approval from an Institutional Review Board was not necessary, as this is a retrospective non-interventional study which reuses existing data. The study’s database was registered on the AP-HM’s health data access portal under number PADS24-120. Data collection For the present study, demographic characteristics (age, sex, place of residence), medical information (having at least 3 comorbidities excluding cancer and diabetes, falls or fractures history in the previous 6 months, cancer site and stage) and geriatric characteristics (Mini Mental State Examination score (MMSE, < 24 indicates impairment [19]), Activities of Daily Living scale score (ADL, < 6 indicates impairment [20]), Instrumental Activities Daily Living scale score (IADL, < 4 indicates impairment [21]) were all obtained from the each patient’s CGA report. Nutritional status was also collected from the CGA report and the French Department of Health’s recommendation was used to define malnutrition [22]. Biological data were collected from the individual CGA. Renal function was assessed using the Cockcroft-Gault creatinine clearance (mL/min) value to determine the stage of chronic kidney disease (CKD, stage 1 to stage 5). The actual HbA1c level for each patient was collected, and the individual target HbA1c range determined for each patient based on the SFD 2021 guidelines and the patient’s profile according to their CGA [10]. Medication data were collected from the individual MR and included the number of medications, the number of antidiabetics, and glucose-lowering agents prescribed. During the MRs, each prescribed drug was assessed based on the patient’s history, comorbidities and the risk/benefit balance, while taking available therapeutic guidelines into consideration. All recommendations regarding a patient’s therapeutic management were highlighted in the MR and summarized in the final CGA report. From each patient’s MR, we collected the following data: number of therapeutic-related issues, number of diabetes-related therapeutic issues (DTI) (defined as a deviation from the SFD’s 2021 guidelines [10]), the type of DTI, the glucose-lowering agent involved, and the type of recommendation proposed by the clinical pharmacist. Two groups of patients were defined: patients with no DTI (DTI = 0) and patients with at least one DTI (DTI ≥ 1). Statistical analysis Results are presented as mean ± standard deviation for quantitative variables, and as numbers and percentages for qualitative variables. The latter were compared between both patient groups (i.e., DTI =0, DTI ≥ 1) using a univariate analysis with Chi-square or Fisher’s exact test according to the conditions of application. A multivariate logistic regression analysis was performed using forward stepwise selection to identify factors associated with having at least one DTI. Variables with a p-value < 0.2 in the univariate analysis and/or those considered clinically and practically relevant were tested in the multivariate model. The results are expressed as odds ratio (OR) and their confidence interval (CI), with the threshold set to 95%. Statistical analyses were performed using R++ version 1.6.15 software (© 2019-2022 Zebrys). The significant threshold was set at 5%. Results Characteristics of the study population Among the 738 outpatients in our geriatric oncology unit who underwent a CGA between January 2022 and December 2023, 190 had comorbid diabetes and were included in the present study. Demographic, medical, biological and therapeutic characteristics of the study population are detailed in Table 1 . Mean age was 79.5 ± 5.6 years, and 61.1% of the patients were male. A large majority of patients (91.6%) lived at home, half of whom needed a nurse. The CGA analysis revealed that 45.5% of patients were dependent in daily activities, and that 33.3% had cognitive impairment. More than half (63.7%) were at risk of malnutrition or were malnourished. Slightly less than two-thirds (62.1%) had more than three comorbidities (i.e., excluding cancer and diabetes). A large majority (87.9%) suffered from cardiovascular disease, and half presented chronic kidney disease (50.2%). A quarter (24.2%) of the patients had fallen or had a fracture in the previous 6 months. With regard to cancer, approximately one-third of the patients had lung cancer (27.9%), and a quarter digestive cancer (24.2%); the majority had advanced or metastatic cancer (60.5%). A large majority of patients were prescribed more than five drugs (89.5%) and nearly one-third more than 10 drugs (36.3%) excluding cancer treatment drugs. With regard to the pharmacological management of T2DM, overall, patients were prescribed 1.8 ± 1.1 antidiabetics, with a quarter being prescribed at least 3 such drugs (25.3%). The glucose-lowering agents most frequently prescribed were metformin (57.4%), insulin (36.8%), dipeptidyl peptidase-4 inhibitors (DPP4i, 23.2%) and sulfonylureas (18.4%). In line with the CGA report and the SFD’s 2021 guidelines, 17 (9.0%) patients were defined as having “healthy/good health” (i.e., functionally and cognitively intact with a good life expectancy (HbA1c target ≤ 7%)), 149 (78.4%) had “frail/intermediate health” (i.e., functionally dependent or have multiple coexisting chronic comorbidities or cognitive impairment (HbA1c target > 7% and ≤ 8%)), and 24 (12.6%) had “dependent/poor health” (i.e., receiving end-of-life care (HbA1c target > 8% and < 9%)). For patients under 75 years old with an estimated life expectancy of less than five years, the selected maximum HbA1c threshold was 8%. Actual HbA1c values were available for 137 patients (72.1%), and the mean actual HbA1c was 6.89% ± 1.03%. For each patient, the actual HbA1c was compared with the individual target HbA1c range as per the SFD’s 2021 guidelines ( Table 2 ). Only 50/137 patients (36.5%) had an actual HbA1c in line with the recommended target range, 70/137 patients (51.1%) had an actual HbA1c below it, and 17/137 patients (12.4%) above it. Diabetes-related therapeutic issues and recommendations A total of 1,428 therapeutic-related issues were identified by our unit’s clinical pharmacist, corresponding to a mean of 7.5 ± 2.8 issues per patient ( Table 3 ). Of these, 170 were DTI; 67.9% of patients had at least one DTI. More specifically, 75 DTI (44.1%) were related to blood test analyses, specifically when the actual HbA1c was either below or above the recommended individual target range and 95 DTI (55.9%) were identified as drug-related problems. Of the latter, 61 DTI (64.2%) were associated with a prescribed medication that was inappropriate for patients of advanced age because of a high risk of hypoglycaemia or malnutrition. Prescribed sulfonylureas, glinides and glucagon-like peptide 1 (GLP-1) analogues accounted for significant proportions of these 61 DTI (55.7%, 29.5%, and 14.8%, respectively). Thirty DTI (31.6%) were associated with inappropriate doses or regimens; of these, 14 were due to failure to adjust metformin or DPP4i to renal function, while 16 were due to non-compliant metformin dosage regimens (e.g., once-daily prescription instead of twice or three times daily). Three DTI were associated with medications with contraindications (3.2%) due to renal function with sulfonylureas and sodium-glucose co-transporter-2 inhibitors (SGLT2i), and 1 DTI was associated with therapeutic duplication (1.1%) where two SGLT2i were prescribed. A total of 288 recommendations were made ( Table 3 ) in the MRs carried out and were communicated to the patients’ health practitioners by the unit’s geriatrician (n, %), as follows: HbA1c blood test monitoring or self-monitoring of blood glucose (138, 47.9%), stopping a medication (64, 22.2%), switching a glucose-lowering agent (42, 14.6%), adjusting dosage (36, 12.5%) and starting a medication (8, 2.8%). Concerning stopping/switching recommendations, the main glucose-lowering agents recommended for discontinuation were sulfonylureas (29.2%), metformin (22.6%), glinides (15.1%). The starting/switching recommendations principally concerned DPP4i (48.9%) and metformin (38.3%). Factors associated with the presence of at least one diabetes-related therapeutic issue (Table 4) The analysis revealed a significantly higher proportion of patients aged over 75 in the group with at least one DTI (OR 2.68, 95% CI 1.19-5.99). With regard to the CGAs, cognitive disorders (MMSE < 24) were identified as a significant protective factor for having a DTI (OR 0.46, 95% CI 0.23-0.91). Similarly, patients with at least three comorbidities were less likely – but not significantly so – to have a DTI (OR 0.52, 95% CI 0.27-1.00). Of the recorded comorbidities, none was significantly associated with having a DTI, including renal failure. Conversely, patients reporting falls or fractures in the previous 6 months were significantly more likely to have a DTI (OR 2.77, 95% CI 1.20-6.37). Among the 137 patients whose actual HbA1c level was compared with the recommended individual target range, a significant association was observed between having at least one DTI and having an HbA1c level below the individual target (OR 10.79, 95% CI 4.08-28.49). Patients taking at least three antidiabetics were significantly more likely to have a DTI (OR 2.50, 95% CI 1.12-5.58). With regard to glucose-lowering agents, the proportion of patients receiving treatment with metformin, glinides, SGLT2i and/or GLP-1 analogues was significantly higher in the DTI group compared to the no DTI group. Conversely, insulin-treated patients were less likely - although not significantly so - to have at least one DTI (OR 0.57, 95% CI 0.31-1.06). All patients treated with sulfonylureas had at least one DTI. After logistic regression, an HbA1c level below the individual target range ( p-value < 0.001) and prescription of at least 3 antidiabetics ( p-value < 0.05) were still associated with having at least one DTI. Moreover, cognitive impairment (MMSE < 24) was still a protective factor after logistic regression ( p-value < 0.05). Discussion Our geriatric study population of patients living with cancer who had comorbid diabetes were characterised by a high percentage of frailties and geriatric syndromes (91% of patients were defined as frail or dependent). This can be partly explained by the fact that only the most vulnerable cancer patients (i.e., G8 score showing impairment) were referred to our unit for CGA. Specifically, nearly two-thirds of patients experienced IADL impairment, half had ADL impairment, one-third suffered from cognitive impairment, and two-thirds had poor nutritional status. The prevalence of these four key health vulnerability criteria was greater than in other studied diabetic geriatric populations, for example in the GERODIAB observational cohort [ 9 ]. The principal reasons for this were that our population was older (79.5 ± 5.6 years) and, most importantly, they all had cancer. Frailties and geriatric syndromes – including falls, cognitive impairment, sarcopenia, depression and polypharmacy [ 23 ]– can be caused by cancer and related therapy. Different studies have demonstrated that older adults with cancer experienced a higher prevalence of frailties or geriatric syndromes than those without cancer [ 24 ]; Handfort et al. reported a frailty rate of approximately 40–50% in this population [ 25 ]. In contrast, the prevalence of other frailties and geriatric syndromes in our study population, such as polymorbidity (62.1% of patients had 3 or more comorbidities) and polypharmacy (89.5% of patients were prescribed 5 or more medications), are consistent with findings by Baretella et al. who highlighted the overtreatment of multimorbid older patients with T2DM [ 26 ]. Considering the characteristics of the study population in terms of frailties and geriatric syndromes, the mean actual HbA1c of our population was notably lower (6.89% ± 1.03%) than the target HbA1c range recommended by the SFD’s 2021 guidelines [ 10 ]. It was also much lower than that in two other studies (HbA1c 7.56%): one with a heterogeneous older diabetic population (GERODIAB [ 27 ]) and one with older adults with T2DM and cancer (ONCODIAB [ 28 ]). In contrast, it was very similar to that observed in an older Ontario population with T2DM (HbA1c 6.93%) where 61% of individuals were overtreated for intensive glycaemic control (HbA1c < 7%) [ 12 ]. In our study, 63.5% of patients exhibited HbA1c levels that were outside the individually tailored target range; of these, more than three-quarters were below this range. To some extent, this finding reflects the results of a recent French study which found that only 36% of patients had matching actual and target HbA1c levels, yet unlike us, observed that actual HbA1c levels were predominantly higher than the target range [ 7 ]. Overall, our findings highlight a certain tendency for practitioners to select more aggressive HbA1c targets than those recommended in the SFD’s guidelines; this is consistent with a recent US survey where half of the physicians involved selected HbA1c targets lower than guidelines for persons with intermediate and poor health [ 29 ]. In our study, patients with an individual HbA1c target of less than 7% had localised cancer, were functionally and cognitively intact, and had a good life expectancy. It is important to highlight that measuring HbA1c may not be accurate for glycaemic control for several conditions which are frequent in older patients with cancer, including anaemia, chronic kidney disease, recent blood loss or transfusion, iron or vitamin deficiency, and anaemia treatments. This is because any alteration in erythropoiesis and/or the lifespan of red blood cells will influence haemoglobin level. In such circumstances, self-monitoring of blood glucose measurement is the preferred method for guiding treatment decisions [ 30 ]. In the present case, only fasting blood glucose data were available for the MR and there was no way of checking the fasting status retrospectively. Nevertheless, the fact that over half of our patients had an actual HbA1c level below the individual target range suggests that T2DM was overtreated. More specifically, 25.3% of the patients were treated with at least three antidiabetics, whereas the SFD recommends monotherapy or dual metformin +/- DPP4i therapy and insulin therapy in case of persistent hyperglycaemia. The three glucose-lowering agents most frequently observed (metformin, DPP4i, insulin) in our patients reflect SFD guidelines. More than half were treated with metformin, which is unanimously recommended as the first-line therapy. There were relatively few prescriptions for GLP-1 analogues and SGLT2i. This is not unexpected, given the SFD’s guidelines to use these molecules with caution in frail patients, and primarily for cardiovascular or renal protection rather than for the glycaemic control [ 31 ]. Furthermore, GLP-1 analogues and SGLT2i were prescribed less frequently in 2022-23 than today (2024). These new therapeutic classes offer unprecedented benefits in terms of cardiovascular and renal protection, and new recommendations are increasingly encouraging their use in older adults. However, the benefits and side effects of these drugs need to be well understood when prescribing them to these often frail patients. Sulfonylureas and glinides accounted for 18.4% and 11.6% of prescriptions, respectively. This is consistent with the prescribing patterns observed by J. Doucet et al. in 2014–2015 [ 13 ], and suggests inertia in the evolution of prescribing practices over a 10-year period, especially as these medications have not been included in diabetes management recommendations for almost a decade, and moreover, should be avoided in older adults because of the high risk of hypoglycaemia [ 32 ]. Furthermore, the risk of poor glycaemic control and hypoglycaemia may be increased with polypharmacy (i.e., ≥ 5 prescribed medications), which was identified in 89.5% of patients in our study (36.3% having 10 prescribed medications). This is considerably higher than the pooled prevalence of 50% reported in a meta-analysis conducted by Remelli et al. [ 33 ]. To ascertain the circumstances in which de-intensification of antihyperglycaemic treatment may be appropriate, we identified the factors associated with having a DTI. The MRs revealed that two-thirds of our studied population had suboptimal therapeutic management of their T2DM. As expected, an HbA1c level below the individual target was significantly and strongly associated with having a DTI. The prescription of more than three antidiabetics was also associated with a significantly higher risk of suboptimal management when compared with established guidelines. Cognitive disorders were retained as a protective factor in the logistic model. Patients with cognitive alterations are less likely to be involved in diabetes self-care and are at higher risk of severe hypoglycaemia due to their inability to identify or report hypoglycaemia symptoms [ 34 ]. This suggests that prescribers may be more inclined to simplify treatment regimens for these patients. Similarly, the presence of at least three comorbidities seemed to be a protective factor to having a DTI, but not significantly. This may be because these patients are typically managed by one or more organ specialists who are able to adapt antidiabetic treatment in accordance with guidelines. The majority of DTI pertaining to problems with prescribed medications were associated with the specific characteristics of older patients (high risk of hypoglycaemia, risk of malnutrition, etc.) and mainly concerned the incorrect prescription of insulin secretagogues (sulfonylureas or glinides) and GLP-1 analogues. Given these patients’ frailties and geriatric syndromes, the MRs recommended either discontinuing insulin secretagogues and/or GLP-1 analogues or switching to metformin and/or DPP4i. In the univariate analysis, we found an association between having a DTI and a history of falls or fractures in the previous six months. Of these patients, 69.6% were being treated with sulfonylureas, glinides or insulin, which are glucose-lowering agents that significantly increase the risk of falls when combined with polypharmacy [ 35 ]. Falls might be attributed to recurrent hypoglycaemia, which may in turn lead to hypoglycaemia being unrecognised in older patients, given their lower sensitivity to hypoglycaemia [ 36 ]. The proportion of sulfonylureas discontinuation recommendations in the MRs was comparable to that observed in the ONCODIAB study [ 28 ]. However, the proportion of recommendations for discontinuing glinides, metformin and DPP4i was twice as high. More specifically, metformin discontinuation was suggested for many patients on a once-daily prescribed dose of metformin (≤ 1000 mg prescribed 1x/day) whose actual HbA1c levels were below the target range; this explains the significant association with having a DTI in the univariate analysis. The same was observed for DPP4i; discontinuation was proposed for patients with dual therapy (DPP4i-metformin) whose HbA1c levels were below the target range. With regard to GLP-1 analogues, prescriptions were associated with having a DTI in the univariate analysis. While this therapeutic class is of particular interest in patients with overweight or cardiovascular T2DM, the risk of worsening undernutrition or sarcopenia is too high in cancer patients to justify its use. Furthermore, although CKD was not present in the logistic model, it is important to highlight that several prescriptions were not adapted to renal function and did not respect contraindications in persons with severe CKD in our study (∼10% of DTI), notably regarding metformin, but also sulfonylureas and DPP4i. This reflects findings from an Italian study [ 37 ], which demonstrated that the prescription of metformin and sulfonylureas was very prevalent in older adults with moderate and severe CKD, and that there was a high risk of adverse effects such as lactic acidosis and severe hypoglycaemia. The present study has limitations. First, as it a retrospective in nature, certain biases may have arisen due to the presence of missing data and the heterogeneity of the study population. Second, 27.9% of patients had no recent actual HbA1c available, making personalised T2DM management more complex. This can be attributed to the fact that HbA1c is not systematically measured during CGA in our unit, particularly when the patient has already undergone a blood test previously, but without any HbA1c measurement. Third, the treatment data set comprised solely the most recent prescriptions (within the previous three months). Most prescriptions were sourced from GPs, which is consistent with the French DIABASIS survey which found that 93% of patients were registered with GP for diabetes care [ 38 ]. However, it was not possible to determine whether patients were registered with a diabetologist but had their prescriptions renewed by a GP, or whether they were only registered with a GP for diabetes care. Conclusion This study reveals overly aggressive glycaemic control in our frail older population of patients with comorbid cancer and T2DM, and highlights poor clinical adherence to guidelines in the pharmacological management of T2DM. More specifically, older patients with intermediate or poor health tended to have more aggressive individual HbA1c targets than those recommended and therefore tended to be overtreated. Most of the DTI concerned problems related to the prescription of insulin secretagogues, which are widely not recommended in older adults because of the high risk of hypoglycaemia. This finding highlights the need for physicians to adopt updated practices that facilitate personalised treatment management. With their multidisciplinary teams of geriatricians, dieticians, psychologists, and clinical pharmacists, geriatric day hospitals provide patient-centred care which is essential to detect ageing-related complications. Geriatrician-pharmacist collaborations in these structures lead to a more comprehensive understanding of the patient’s profile, which in turn guides therapeutic choices based on individualised glycaemic targets. Moreover, active communication between geriatricians and GPs upon the completion of a CGA would foster more comprehensive implementation of T2DM recommendations in older cancer adults. Declarations Competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest. Funding sources This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Informed consent Considering that routinely collected data were anonymised, informed consent was not required. Ethics approval In accordance with French law, approval from an Institutional Review Board was not necessary, as this is a retrospective non-interventional study which reuses existing data. The study’s database was registered on the AP-HM’s health data access portal under number PADS24-120. References ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. 13. Older Adults: Standards of Care in Diabetes-2023. Diabetes Care 2023;46:S216–29. https://doi.org/10.2337/dc23-S013. Magliano DJ, Boyko EJ, IDF Diabetes Atlas 10th edition scientific committee. IDF DIABETES ATLAS. 10th ed. Brussels: International Diabetes Federation; 2021. Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr 2017;17:230. https://doi.org/10.1186/s12877-017-0621-2. Vischer U-M, Bauduceau B, Bourdel-Marchasson I, Blickle J-F, Constans T, Fagot-Campagna A, et al. A call to incorporate the prevention and treatment of geriatric disorders in the management of diabetes in the elderly. Diabetes Metab 2009;35:168–77. https://doi.org/10.1016/j.diabet.2009.02.003. Bradley D, Hsueh W. Type 2 Diabetes in the Elderly: Challenges in a Unique Patient Population. J Geriatr Med Gerontol 2016;2:14. https://doi.org/10.23937/2469-5858/1510014. Bonds DE, Miller ME, Bergenstal RM, Buse JB, Byington RP, Cutler JA, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010;340:b4909. https://doi.org/10.1136/bmj.b4909. Khunti K, Davies M, Majeed A, Thorsted BL, Wolden ML, Paul SK. Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study. Diabetes Care 2015;38:316–22. https://doi.org/10.2337/dc14-0920. Huang ES. Individualizing Care for Older Adults With Diabetes Amid the Revolution in Pharmacotherapy. JAMA Intern Med 2024;184:435. https://doi.org/10.1001/jamainternmed.2023.8559. Doucet J, Verny C, Balkau B, Scheen AJ, Bauduceau B. Haemoglobin A1c and 5-year all-cause mortality in French type 2 diabetic patients aged 70 years and older: The GERODIAB observational cohort. Diabetes & Metabolism 2018;44:465–72. https://doi.org/10.1016/j.diabet.2018.05.003. Darmon P, Bauduceau B, Bordier L, Detournay B, Gourdy P, Guerci B, et al. Prise de position de la Société Francophone du Diabète (SFD) sur les stratégies d’utilisation des traitements anti-hyperglycémiants dans le diabète de type 2 – 2021. Médecine Des Maladies Métaboliques 2021;15:781–801. https://doi.org/10.1016/j.mmm.2021.10.014. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022;45:2753–86. https://doi.org/10.2337/dci22-0034. Lega IC, Campitelli MA, Austin PC, Na Y, Zahedi A, Leung F, et al. Potential diabetes overtreatment and risk of adverse events among older adults in Ontario: a population-based study. Diabetologia 2021;64:1093–102. https://doi.org/10.1007/s00125-020-05370-7. Doucet J, Guérin O, Hilbert C, Bordier L, Verny C, Marchand C, et al. Changes in antidiabetic drug prescription patterns during follow-up of the GERODIAB cohort. Comparison with professional recommendations. Diabetes Epidemiology and Management 2023;9:100084. https://doi.org/10.1016/j.deman.2022.100084. Mohile SG, Dale W, Somerfield MR, Schonberg MA, Boyd CM, Burhenn PS, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. J Clin Oncol 2018;36:2326–47. https://doi.org/10.1200/JCO.2018.78.8687. Scotté F, Bossi P, Carola E, Cudennec T, Dielenseger P, Gomes F, et al. Addressing the quality of life needs of older patients with cancer: a SIOG consensus paper and practical guide. Ann Oncol 2018;29:1718–26. https://doi.org/10.1093/annonc/mdy228. Loh KP, Liposits G, Arora SP, Neuendorff NR, Gomes F, Krok-Schoen JL, et al. Adequate assessment yields appropriate care—the role of geriatric assessment and management in older adults with cancer: a position paper from the ESMO/SIOG Cancer in the Elderly Working Group. ESMO Open 2024;9:103657. https://doi.org/10.1016/j.esmoop.2024.103657. Couderc A-L, Boisseranc C, Rey D, Nouguerede E, Greillier L, Barlesi F, et al. Medication Reconciliation Associated with Comprehensive Geriatric Assessment in Older Patients with Cancer: ChimioAge Study. CIA 2020;15:1587–98. https://doi.org/10.2147/CIA.S262209. Soubeyran P, Bellera C, Goyard J, Heitz D, Curé H, Rousselot H, et al. Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study. PLoS One 2014;9:e115060. https://doi.org/10.1371/journal.pone.0115060. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98. https://doi.org/10.1016/0022-3956(75)90026-6. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. the index of ADL: a standardized measure of biological and psychosocial function. JAMA 1963;185:914–9. https://doi.org/10.1001/jama.1963.03060120024016. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179–86. Haute Autorite ́ de Sante ́ (HAS) Diagnostic de la dénutrition chez la personne de 70 ans et plus [https://www.has-sante.fr/upload/docs/application/pdf/2021-11/reco368_recommandations_denutrition_pa_cd_20211110_v1.pdf (Accessed August)] n.d. Magnuson A, Sattar S, Nightingale G, Saracino R, Skonecki E, Trevino KM. A Practical Guide to Geriatric Syndromes in Older Adults With Cancer: A Focus on Falls, Cognition, Polypharmacy, and Depression. Am Soc Clin Oncol Educ Book 2019;39:e96–109. https://doi.org/10.1200/EDBK_237641. Mohile SG, Fan L, Reeve E, Jean-Pierre P, Mustian K, Peppone L, et al. Association of cancer with geriatric syndromes in older Medicare beneficiaries. J Clin Oncol 2011;29:1458–64. https://doi.org/10.1200/JCO.2010.31.6695. Handforth C, Clegg A, Young C, Simpkins S, Seymour MT, Selby PJ, et al. The prevalence and outcomes of frailty in older cancer patients: a systematic review. Ann Oncol 2015;26:1091–101. https://doi.org/10.1093/annonc/mdu540. Baretella O, Alwan H, Feller M, Aubert CE, Del Giovane C, Papazoglou D, et al. Overtreatment and associated risk factors among multimorbid older patients with diabetes. Journal of the American Geriatrics Society 2023;71:2893–901. https://doi.org/10.1111/jgs.18465. Doucet J, Le Floch J-P, Bauduceau B, Verny C, SFD/SFGG Intergroup. GERODIAB: Glycaemic control and 5-year morbidity/mortality of type 2 diabetic patients aged 70 years and older: 1. Description of the population at inclusion. Diabetes Metab 2012;38:523–30. https://doi.org/10.1016/j.diabet.2012.07.001. Paris J, Legris P, Devaux M, Bost S, Gueneau P, Rossi C, et al. Impact of a Tripartite Collaboration between Oncologist, Pharmacist and Diabetologist in the Management of Patients with Diabetes Starting Chemotherapy: The ONCODIAB Trial. Cancers 2023;15:4544. https://doi.org/10.3390/cancers15184544. Pilla SJ, Jalalzai R, Tang O, Schoenborn NL, Boyd CM, Golden SH, et al. A National Physician Survey of Deintensifying Diabetes Medications for Older Adults With Type 2 Diabetes. Diabetes Care 2023;46:1164–8. https://doi.org/10.2337/dc22-2146. Doucet J, Gourdy P, Meyer L, Benabdelmoumene N, Bourdel-Marchasson I. Management of Glucose-Lowering Therapy in Older Adults with Type 2 Diabetes: Challenges and Opportunities. CIA 2023;Volume 18:1687–703. https://doi.org/10.2147/CIA.S423122. Bauduceau B, Bordier L, Doucet J. Interest and place of new therapeutic classes in the treatment of elderly diabetic patients. Diabetes Metab 2023;49:101431. https://doi.org/10.1016/j.diabet.2023.101431. Strain WD, Hope SV, Green A, Kar P, Valabhji J, Sinclair AJ. Type 2 diabetes mellitus in older people: a brief statement of key principles of modern day management including the assessment of frailty. A national collaborative stakeholder initiative. Diabet Med 2018;35:838–45. https://doi.org/10.1111/dme.13644. Remelli F, Ceresini MG, Trevisan C, Noale M, Volpato S. Prevalence and impact of polypharmacy in older patients with type 2 diabetes. Aging Clin Exp Res 2022;34:1969–83. https://doi.org/10.1007/s40520-022-02165-1. Sinclair AJ, Girling AJ, Bayer AJ. Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. Diabetes Research and Clinical Practice 2000;50:203–12. https://doi.org/10.1016/S0168-8227(00)00195-9. Lipska KJ, Krumholz H, Soones T, Lee SJ. Polypharmacy in the Aging Patient. JAMA 2016;315:1034–45. https://doi.org/10.1001/jama.2016.0299. Freeman J. Management of hypoglycemia in older adults with type 2 diabetes. Postgrad Med 2019;131:241–50. https://doi.org/10.1080/00325481.2019.1578590. Solini A, Penno G, Bonora E, Fondelli C, Orsi E, Trevisan R, et al. Age, renal dysfunction, cardiovascular disease, and antihyperglycemic treatment in type 2 diabetes mellitus: findings from the Renal Insufficiency and Cardiovascular Events Italian Multicenter Study. J Am Geriatr Soc 2013;61:1253–61. https://doi.org/10.1111/jgs.12381. Mosnier-Pudar H, Hochberg G, Eschwege E, Virally M-L, Halimi S, Guillausseau PJ, et al. How do patients with type 2 diabetes perceive their disease? Insights from the French DIABASIS survey. Diabetes Metab 2009;35:220–7. https://doi.org/10.1016/j.diabet.2009.02.001. Tables Tables 1 to 4 are available in the Supplementary Files section. 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Correard","email":"","orcid":"","institution":"Assistance Publique Hôpitaux de Marseille, Hôpital Timone, Service Pharmacie","correspondingAuthor":false,"prefix":"","firstName":"Florian","middleName":"","lastName":"Correard","suffix":""},{"id":374762785,"identity":"09a600a5-dbbe-480d-ba11-e8f28831f208","order_by":2,"name":"Coline Montegut","email":"","orcid":"","institution":"Assistance Publique Hôpitaux de Marseille, Hôpital Sainte Marguerite, Service de médecine interne, gériatrie et thérapeutique","correspondingAuthor":false,"prefix":"","firstName":"Coline","middleName":"","lastName":"Montegut","suffix":""},{"id":374762786,"identity":"f5d01137-5006-486f-8068-0ff735ba0c24","order_by":3,"name":"Jérémie Nakache","email":"","orcid":"","institution":"Assistance Publique Hôpitaux de Marseille, Hôpital Timone, Service 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Université, Centre d'Etudes et de Recherche sur les Services de Santé et la qualité de vie (CEReSS)","correspondingAuthor":false,"prefix":"","firstName":"Stéphane","middleName":"","lastName":"Honoré","suffix":""},{"id":374762790,"identity":"d5e02403-7e2a-4b99-9bb2-088dba68add0","order_by":7,"name":"Aurélie Daumas","email":"","orcid":"","institution":"Assistance Publique Hôpitaux de Marseille, Hôpital Sainte Marguerite, Service médecine interne, gériatrie et thérapeutique","correspondingAuthor":false,"prefix":"","firstName":"Aurélie","middleName":"","lastName":"Daumas","suffix":""},{"id":374762791,"identity":"2ecfbbaa-d722-42a1-b870-6f11cb7abd18","order_by":8,"name":"Anne-Laure Couderc","email":"","orcid":"","institution":"Assistance Publique Hôpitaux de Marseille, Hôpital Sainte Marguerite, Service médecine interne, gériatrie et thérapeutique","correspondingAuthor":false,"prefix":"","firstName":"Anne-Laure","middleName":"","lastName":"Couderc","suffix":""},{"id":374762792,"identity":"428e8c88-5e60-418e-b5d7-c7326f2aaca9","order_by":9,"name":"Charlotte Bérard","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYDACCSB+AGbxgEnGfiDBDMT8eLUkMBhIwLXMbIBokWwgWsuGAwS08M9ufvYhoeJPHT8D78HHFTX3ZDcfP3uAuTCHQcIchx6JO8eMZyScMZCQbOBLNjxzrNh425m8BOaZ2xgkZA5g12IgkWDMkNhmIGFwgMdMsoEtIXHbgRzz37zbGOokcDjMQCL9M1iL/QEe858N/xISN/e/MWAGapHArSUHagsDjxljY1tC4gaJHPxaJG7kFDMknDGWnHGYL1mysS/BeMaNdwlALRI4tfDPSN/M8KFCjp+/vffgx4ZvCbL9/bkHgFpscGpBAGY4CxxBhDUgAx6SVI+CUTAKRsHwBwA4PlF5YKw2bwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-6030-8352","institution":"Assistance Publique Hôpitaux de Marseille, Hôpital Timone, Service Pharmacie","correspondingAuthor":true,"prefix":"","firstName":"Charlotte","middleName":"","lastName":"Bérard","suffix":""}],"badges":[],"createdAt":"2024-10-28 20:26:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5349587/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5349587/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69995563,"identity":"b606ac54-d2d3-45a3-ad70-91f7f8ac6d89","added_by":"auto","created_at":"2024-11-27 10:09:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":441695,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5349587/v1/6a56ebec-8278-4406-8cbe-f35e5390f310.pdf"},{"id":69542100,"identity":"896c9632-a853-4aee-ad06-0ecd832857e7","added_by":"auto","created_at":"2024-11-21 13:04:57","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":32117,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-5349587/v1/6633430adc7f5594957d06f0.docx"}],"financialInterests":"","formattedTitle":"Comparing real-world Type 2 diabetes management with the Francophone Diabetes Society’s recommendations: using comprehensive geriatric assessment-guided medication reviews of frail older adults living with comorbid diabetes and cancer","fulltext":[{"header":"Key summary points","content":"\u003cp\u003eAim: Our aim was to compare the real-world type 2 diabetes management with published guidelines in older outpatients with comorbid cancer, who were referred to our geriatric oncology day hospital for a comprehensive geriatric assessment-guided medication review.\u003c/p\u003e\n\u003cp\u003eFindings: Most patients had overly aggressive glycaemic control and were overtreated. Diabetes-related therapeutic issueswere associated with having an actual HbA1c levels below the individual target range and receiving at least three prescribed antidiabetics drugs.\u003c/p\u003e\n\u003cp\u003eMessage: These findings highlight the lack of adjustment of therapeutic objectives for type 2 diabetes in older adults and the poor adherence of prescribers to the recommendations. Geriatrician-pharmacist collaboration could guide individual therapeutic choices according to individualised glycaemic targets.\u0026nbsp;\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eType 2 diabetes mellitus (T2DM) represents a significant public health issue worldwide; prevalence in older adults is gradually increasing due to population ageing, longer life expectancies, and higher incidence in the general population. It is estimated that almost one-quarter of people with diabetes are aged 70 years or over [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and diabetes prevalence among adults aged 75\u0026ndash;79 years is projected to reach 25% by 2045 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCompared to younger adults, older adults present a more heterogeneous profile in terms of diabetes-related complications, comorbidities, associated polypharmacy (defined here as taking at least five prescribed medications per day [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]) and functional status [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Moreover, the aging process can result in alterations to pharmacokinetic and pharmacodynamic parameters, influencing therapeutic drug responses. In addition, impaired counter-regulatory mechanisms render older adults more vulnerable to adverse effects, particularly hypoglycaemia [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The latter increases the risk of cardiovascular events and mortality [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]; accordingly, older people at high risk of falls, malnutrition or neurocognitive decline need to be especially careful.\u003c/p\u003e \u003cp\u003eAll these factors highlight the challenges clinicians face in providing adequate pharmacological T2DM management to older adults. Advanced age should never be an obstacle to diabetes treatment, but medication prescriptions for older people who are frail or who have multiple comorbidities may need to be adjusted for safety and tolerability reasons. Moreover, deprescribing can avoid unnecessary medication or medication-related harms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In terms of persons with diabetes, based on results from the French study GERODIAB showing that glycated haemoglobin (HbA1c) thresholds are one of the main factors influencing survival in the older population [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], the Francophone Diabetes Society (SFD) recommends less stringent glycaemic control for frail and dependent older adults than for the healthy general population, and a more flexible therapeutic approach to managing the disease [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) also recommend a personalised approach to treatment based on individual characteristics and comorbidities [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Despite this, there is evidence of persistent overtreatment of older adults with T2DM [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and insufficient compliance with diabetes guidelines, probably due to therapeutic inertia on the part of prescribers [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eComprehensive geriatric assessment (CGA) is a validated approach in the management of older adults with cancer [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. According to the International Society of Geriatric Oncology (SIOG) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], close cooperation between geriatricians and clinical pharmacists during CGAs leads to high-quality medication reviews (MRs) and ensures that adverse side effects of treatments are avoided [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. For several years now, our geriatric oncology day hospital unit has performed CGA-guided MRs, as we believe that by taking into account social determinants of health, barriers to care, comorbidities, the level of hyperglycaemia, the risk of medication-related complications, and patient susceptibility to medication-related side effects, more personalized - and therefore more effective - T2DM management can be offered. In the two last years, our CGA-guided MRs have highlighted considerable heterogeneity in the management of T2DM in outpatients with comorbid diabetes who are referred to our unit. High-quality comorbid diabetes control and management is essential in older cancer patients requiring systemic treatment. In this context, the present study aimed to: (i) compare the real-world management of comorbid T2DM in patients who have cancer with published guidelines [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], (2) provide an overview of the diabetes-related therapeutic issues (DTI) identified and recommendations made in our MRs, and (3) describe the factors associated with having at least one DTI.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a monocentric retrospective observational study. It included all outpatients with comorbid cancer and T2DM referred to the geriatric oncology day unit in the University Hospital of Marseille (AP-HM, France), for a CGA-guided MR between January 2022 and December 2023. French guidelines stipulate that oncologists can only refer patients to the unit prior to initiating systemic oncological treatment, if they have an impaired Geriatric 8 (G8) score (≤ 14 out of 17), or if their G8 score is normal but they have suspected frailties not identified by the G8 scale (e.g., depression or loss of autonomy)\u0026nbsp;[18]. CGAs and MRs are conducted by, respectively, a geriatrician and a clinical pharmacist in our day hospital unit. At the end of each CGA, the geriatrician contacts the patient’s general practitioner (GP) and oncologist to communicate the various medication modifications that the unit has already made or believes should be made (i.e., recommendations).\u003c/p\u003e\n\u003cp\u003eIn accordance with French law, approval from an Institutional Review Board was not necessary, as this is a retrospective non-interventional study which reuses existing data. The study’s database was registered on the AP-HM’s health data access portal under number PADS24-120.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor the present study, demographic characteristics (age, sex, place of residence), medical information (having at least 3 comorbidities excluding cancer and diabetes, falls or fractures history in the previous 6 months, cancer site and stage) and geriatric characteristics (Mini Mental State Examination score (MMSE, \u0026lt; 24 indicates impairment\u0026nbsp;[19]), Activities of Daily Living scale score (ADL, \u0026lt; 6 indicates impairment\u0026nbsp;[20]), Instrumental Activities Daily Living scale score (IADL, \u0026lt; 4 indicates impairment\u0026nbsp;[21]) were all obtained from the each patient’s CGA report. Nutritional status was also collected from the CGA report and the French Department of Health’s recommendation was used to define malnutrition\u0026nbsp;[22].\u003c/p\u003e\n\u003cp\u003eBiological data were collected from the individual CGA. Renal function was assessed using the Cockcroft-Gault creatinine clearance (mL/min) value to determine the stage of chronic kidney disease (CKD, stage 1 to stage 5). The actual HbA1c level for each patient was collected, and the individual target HbA1c range determined for each patient based on the SFD 2021 guidelines and the patient’s profile according to their CGA\u0026nbsp;[10].\u003c/p\u003e\n\u003cp\u003eMedication data were collected from the individual MR and included the number of medications, the number of antidiabetics, and glucose-lowering agents prescribed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDuring the MRs, each prescribed drug was assessed based on the patient’s history, comorbidities and the risk/benefit balance, while taking available therapeutic guidelines\u0026nbsp;into consideration. All recommendations regarding a patient’s therapeutic management were highlighted in the MR and summarized in the final CGA report. From each patient’s MR, we collected the following data: number of therapeutic-related issues, number of diabetes-related therapeutic issues (DTI) (defined as a deviation from the SFD’s 2021 guidelines\u0026nbsp;[10]), the type of DTI, the glucose-lowering agent involved, and the type of recommendation proposed by the clinical pharmacist.\u003c/p\u003e\n\u003cp\u003eTwo groups of patients were defined: patients with no DTI (DTI = 0) and patients with at least one DTI (DTI ≥ 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResults are presented as mean ± standard deviation for quantitative variables, and as numbers and percentages for qualitative variables. The latter were compared between both patient groups (i.e., DTI =0, DTI ≥ 1) using a univariate analysis with Chi-square or Fisher’s exact test according to the conditions of application. A multivariate logistic regression analysis was performed using forward stepwise selection to identify factors associated with having at least one DTI. Variables with a p-value \u0026lt; 0.2 in the univariate analysis and/or those considered clinically and practically relevant were tested in the multivariate model. The results are expressed as odds ratio (OR) and their confidence interval (CI), with the threshold set to 95%. Statistical analyses were performed using R++ version 1.6.15 software (© 2019-2022 Zebrys). The significant threshold was set at 5%.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eCharacteristics of the study population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 738 outpatients in our geriatric oncology unit who underwent a CGA between January 2022 and December 2023, 190 had comorbid diabetes and were included in the present study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDemographic, medical, biological and therapeutic characteristics of the study population are detailed in \u003cstrong\u003eTable 1\u003c/strong\u003e. Mean age was 79.5 ± 5.6 years, and 61.1% of the patients were male. A large majority of patients (91.6%) lived at home, half of whom needed a nurse. The CGA analysis revealed that 45.5% of patients were dependent in daily activities, and that 33.3% had cognitive impairment. More than half (63.7%) were at risk of malnutrition or were malnourished. Slightly less than two-thirds (62.1%) had more than three comorbidities (i.e., excluding cancer and diabetes). A large majority (87.9%) suffered from cardiovascular disease, and half presented chronic kidney disease (50.2%). A quarter (24.2%) of the patients had fallen or had a fracture in the previous 6 months. With regard to cancer, approximately one-third of the patients had lung cancer (27.9%), and a quarter digestive cancer (24.2%); the majority had advanced or metastatic cancer (60.5%).\u003c/p\u003e\n\u003cp\u003eA large majority of patients were prescribed more than five drugs (89.5%) and nearly one-third more than 10 drugs (36.3%) excluding cancer treatment drugs. With regard to the pharmacological management of T2DM, overall, patients were prescribed 1.8\u0026nbsp;± 1.1 antidiabetics, with a quarter being prescribed at least 3 such drugs (25.3%). The glucose-lowering agents most frequently prescribed were metformin (57.4%), insulin (36.8%), dipeptidyl peptidase-4 inhibitors (DPP4i, 23.2%) and sulfonylureas (18.4%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn line with the CGA report and the\u0026nbsp;SFD’s\u0026nbsp;2021 guidelines, 17 (9.0%) patients were defined as having “healthy/good health”\u0026nbsp;(i.e., functionally and cognitively intact with a good life expectancy\u0026nbsp;(HbA1c\u0026nbsp;target ≤ 7%)), 149 (78.4%) had “frail/intermediate health” (i.e.,\u0026nbsp;functionally dependent or have multiple coexisting chronic comorbidities or cognitive impairment\u0026nbsp;(HbA1c\u0026nbsp;target\u0026nbsp;\u0026gt; 7% and\u0026nbsp;≤ 8%)),\u0026nbsp;and 24 (12.6%) had “dependent/poor health” (i.e.,\u0026nbsp;receiving end-of-life care\u0026nbsp;(HbA1c\u0026nbsp;target\u0026nbsp;\u0026gt; 8% and\u0026nbsp;\u0026lt; 9%)). For patients under 75 years old with an estimated life expectancy of less than five years, the selected maximum HbA1c threshold was 8%. Actual HbA1c values were available for 137 patients (72.1%), and the mean actual HbA1c was 6.89% ± 1.03%. For each patient, the actual HbA1c was compared with the individual target HbA1c range as per the\u0026nbsp;SFD’s \u0026nbsp;2021 guidelines (\u003cstrong\u003eTable 2\u003c/strong\u003e). Only 50/137 patients (36.5%) had an actual HbA1c in line with the recommended target range, 70/137 patients (51.1%) had an actual HbA1c below it, and 17/137 patients (12.4%) above it.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiabetes-related therapeutic issues and recommendations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 1,428 therapeutic-related issues were identified by our unit’s clinical pharmacist, corresponding to a mean of 7.5 ± 2.8 issues per patient (\u003cstrong\u003eTable 3\u003c/strong\u003e). Of these, 170 were DTI; 67.9% of patients had at least one DTI. More specifically, 75 DTI (44.1%) were related to blood test analyses, specifically when the actual HbA1c was either below or above the recommended individual target range and 95 DTI (55.9%) were identified as drug-related problems. Of the latter, 61 DTI (64.2%) were associated with a prescribed medication that was inappropriate for patients of advanced age because of a high risk of hypoglycaemia or malnutrition. Prescribed sulfonylureas, glinides and glucagon-like peptide 1 (GLP-1) analogues accounted for significant proportions of these 61 DTI (55.7%,\u0026nbsp;29.5%, and 14.8%, respectively). Thirty DTI (31.6%) were associated with inappropriate doses or regimens; of these, 14 were\u0026nbsp;due to failure to adjust metformin or DPP4i to renal function, while 16 were due to non-compliant metformin dosage regimens (e.g., once-daily prescription instead of twice or three times daily). Three DTI were associated with medications with contraindications (3.2%) due to renal function with sulfonylureas and sodium-glucose co-transporter-2 inhibitors (SGLT2i), and 1 DTI was associated with therapeutic duplication (1.1%) where two SGLT2i were prescribed.\u003c/p\u003e\n\u003cp\u003eA total of 288 recommendations were made (\u003cstrong\u003eTable 3\u003c/strong\u003e) in the MRs carried out and were communicated to the patients’ health practitioners by the unit’s geriatrician (n, %), as follows: HbA1c blood test monitoring or self-monitoring of blood glucose (138, 47.9%), stopping a medication (64, 22.2%), switching a glucose-lowering agent (42, 14.6%), adjusting dosage (36, 12.5%) and starting a medication (8, 2.8%). Concerning stopping/switching recommendations, the main glucose-lowering agents recommended for discontinuation were\u0026nbsp;sulfonylureas (29.2%), metformin (22.6%),\u0026nbsp;glinides (15.1%). The starting/switching recommendations principally concerned DPP4i (48.9%) and metformin (38.3%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFactors associated with the presence of at least one diabetes-related therapeutic issue (Table 4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe analysis revealed a significantly higher proportion of patients aged over 75 in the group with at least one DTI (OR 2.68, 95% CI 1.19-5.99). With regard to the CGAs, cognitive disorders (MMSE \u0026lt; 24) were identified as a significant protective factor for having a DTI (OR 0.46, 95% CI 0.23-0.91). Similarly, patients with at least three comorbidities were less likely – but not significantly so – to have a DTI (OR 0.52, 95% CI 0.27-1.00). Of the recorded comorbidities, none was significantly associated with having a DTI, including renal failure. Conversely, patients reporting falls or fractures in the previous 6 months were significantly more likely to have a DTI (OR 2.77, 95% CI 1.20-6.37).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong the 137 patients whose actual HbA1c level was compared with the recommended individual target range, a significant association was observed between having at least one DTI and having an HbA1c level below the individual target (OR 10.79, 95% CI 4.08-28.49). Patients taking at least three antidiabetics were significantly more likely to have a DTI\u0026nbsp;(OR 2.50, 95% CI 1.12-5.58). With regard to\u0026nbsp;glucose-lowering agents, the proportion of patients receiving treatment with metformin, glinides, SGLT2i and/or GLP-1 analogues was significantly higher in the DTI group compared to the no DTI group. Conversely, insulin-treated patients were less likely - although not significantly so - to have at least one DTI (OR 0.57, 95% CI 0.31-1.06). All patients treated with sulfonylureas had at least one DTI.\u003c/p\u003e\n\u003cp\u003eAfter logistic regression, an HbA1c level below the individual target range (\u003cem\u003ep-value\u003c/em\u003e \u0026lt; 0.001) and prescription of at least 3 antidiabetics (\u003cem\u003ep-value\u003c/em\u003e \u0026lt; 0.05) were still associated with having at least one DTI. Moreover,\u0026nbsp;cognitive impairment (MMSE \u0026lt; 24) was still a protective factor after logistic regression\u0026nbsp;(\u003cem\u003ep-value\u003c/em\u003e \u0026lt; 0.05).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur geriatric study population of patients living with cancer who had comorbid diabetes were characterised by a high percentage of frailties and geriatric syndromes (91% of patients were defined as frail or dependent). This can be partly explained by the fact that only the most vulnerable cancer patients (i.e., G8 score showing impairment) were referred to our unit for CGA. Specifically, nearly two-thirds of patients experienced IADL impairment, half had ADL impairment, one-third suffered from cognitive impairment, and two-thirds had poor nutritional status. The prevalence of these four key health vulnerability criteria was greater than in other studied diabetic geriatric populations, for example in the GERODIAB observational cohort [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The principal reasons for this were that our population was older (79.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6 years) and, most importantly, they all had cancer. Frailties and geriatric syndromes \u0026ndash; including falls, cognitive impairment, sarcopenia, depression and polypharmacy [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u0026ndash; can be caused by cancer and related therapy. Different studies have demonstrated that older adults with cancer experienced a higher prevalence of frailties or geriatric syndromes than those without cancer [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]; Handfort et al. reported a frailty rate of approximately 40\u0026ndash;50% in this population [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In contrast, the prevalence of other frailties and geriatric syndromes in our study population, such as polymorbidity (62.1% of patients had 3 or more comorbidities) and polypharmacy (89.5% of patients were prescribed 5 or more medications), are consistent with findings by Baretella et al. who highlighted the overtreatment of multimorbid older patients with T2DM [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConsidering the characteristics of the study population in terms of frailties and geriatric syndromes, the mean actual HbA1c of our population was notably lower (6.89% \u0026plusmn; 1.03%) than the target HbA1c range recommended by the SFD\u0026rsquo;s 2021 guidelines [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. It was also much lower than that in two other studies (HbA1c 7.56%): one with a heterogeneous older diabetic population (GERODIAB [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]) and one with older adults with T2DM and cancer (ONCODIAB [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]). In contrast, it was very similar to that observed in an older Ontario population with T2DM (HbA1c 6.93%) where 61% of individuals were overtreated for intensive glycaemic control (HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;7%) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In our study, 63.5% of patients exhibited HbA1c levels that were outside the individually tailored target range; of these, more than three-quarters were below this range. To some extent, this finding reflects the results of a recent French study which found that only 36% of patients had matching actual and target HbA1c levels, yet unlike us, observed that actual HbA1c levels were predominantly higher than the target range [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Overall, our findings highlight a certain tendency for practitioners to select more aggressive HbA1c targets than those recommended in the SFD\u0026rsquo;s guidelines; this is consistent with a recent US survey where half of the physicians involved selected HbA1c targets lower than guidelines for persons with intermediate and poor health [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In our study, patients with an individual HbA1c target of less than 7% had localised cancer, were functionally and cognitively intact, and had a good life expectancy.\u003c/p\u003e \u003cp\u003eIt is important to highlight that measuring HbA1c may not be accurate for glycaemic control for several conditions which are frequent in older patients with cancer, including anaemia, chronic kidney disease, recent blood loss or transfusion, iron or vitamin deficiency, and anaemia treatments. This is because any alteration in erythropoiesis and/or the lifespan of red blood cells will influence haemoglobin level. In such circumstances, self-monitoring of blood glucose measurement is the preferred method for guiding treatment decisions [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In the present case, only fasting blood glucose data were available for the MR and there was no way of checking the fasting status retrospectively.\u003c/p\u003e \u003cp\u003eNevertheless, the fact that over half of our patients had an actual HbA1c level below the individual target range suggests that T2DM was overtreated. More specifically, 25.3% of the patients were treated with at least three antidiabetics, whereas the SFD recommends monotherapy or dual metformin +/- DPP4i therapy and insulin therapy in case of persistent hyperglycaemia. The three glucose-lowering agents most frequently observed (metformin, DPP4i, insulin) in our patients reflect SFD guidelines. More than half were treated with metformin, which is unanimously recommended as the first-line therapy. There were relatively few prescriptions for GLP-1 analogues and SGLT2i. This is not unexpected, given the SFD\u0026rsquo;s guidelines to use these molecules with caution in frail patients, and primarily for cardiovascular or renal protection rather than for the glycaemic control [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Furthermore, GLP-1 analogues and SGLT2i were prescribed less frequently in 2022-23 than today (2024). These new therapeutic classes offer unprecedented benefits in terms of cardiovascular and renal protection, and new recommendations are increasingly encouraging their use in older adults. However, the benefits and side effects of these drugs need to be well understood when prescribing them to these often frail patients. Sulfonylureas and glinides accounted for 18.4% and 11.6% of prescriptions, respectively. This is consistent with the prescribing patterns observed by J. Doucet et al. in 2014\u0026ndash;2015 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and suggests inertia in the evolution of prescribing practices over a 10-year period, especially as these medications have not been included in diabetes management recommendations for almost a decade, and moreover, should be avoided in older adults because of the high risk of hypoglycaemia [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Furthermore, the risk of poor glycaemic control and hypoglycaemia may be increased with polypharmacy (i.e., \u0026ge; 5 prescribed medications), which was identified in 89.5% of patients in our study (36.3% having 10 prescribed medications). This is considerably higher than the pooled prevalence of 50% reported in a meta-analysis conducted by Remelli et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo ascertain the circumstances in which de-intensification of antihyperglycaemic treatment may be appropriate, we identified the factors associated with having a DTI. The MRs revealed that two-thirds of our studied population had suboptimal therapeutic management of their T2DM. As expected, an HbA1c level below the individual target was significantly and strongly associated with having a DTI. The prescription of more than three antidiabetics was also associated with a significantly higher risk of suboptimal management when compared with established guidelines. Cognitive disorders were retained as a protective factor in the logistic model. Patients with cognitive alterations are less likely to be involved in diabetes self-care and are at higher risk of severe hypoglycaemia due to their inability to identify or report hypoglycaemia symptoms [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. This suggests that prescribers may be more inclined to simplify treatment regimens for these patients. Similarly, the presence of at least three comorbidities seemed to be a protective factor to having a DTI, but not significantly. This may be because these patients are typically managed by one or more organ specialists who are able to adapt antidiabetic treatment in accordance with guidelines.\u003c/p\u003e \u003cp\u003eThe majority of DTI pertaining to problems with prescribed medications were associated with the specific characteristics of older patients (high risk of hypoglycaemia, risk of malnutrition, etc.) and mainly concerned the incorrect prescription of insulin secretagogues (sulfonylureas or glinides) and GLP-1 analogues. Given these patients\u0026rsquo; frailties and geriatric syndromes, the MRs recommended either discontinuing insulin secretagogues and/or GLP-1 analogues or switching to metformin and/or DPP4i. In the univariate analysis, we found an association between having a DTI and a history of falls or fractures in the previous six months. Of these patients, 69.6% were being treated with sulfonylureas, glinides or insulin, which are glucose-lowering agents that significantly increase the risk of falls when combined with polypharmacy [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Falls might be attributed to recurrent hypoglycaemia, which may in turn lead to hypoglycaemia being unrecognised in older patients, given their lower sensitivity to hypoglycaemia [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The proportion of sulfonylureas discontinuation recommendations in the MRs was comparable to that observed in the ONCODIAB study [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, the proportion of recommendations for discontinuing glinides, metformin and DPP4i was twice as high. More specifically, metformin discontinuation was suggested for many patients on a once-daily prescribed dose of metformin (\u0026le;\u0026thinsp;1000 mg prescribed 1x/day) whose actual HbA1c levels were below the target range; this explains the significant association with having a DTI in the univariate analysis. The same was observed for DPP4i; discontinuation was proposed for patients with dual therapy (DPP4i-metformin) whose HbA1c levels were below the target range. With regard to GLP-1 analogues, prescriptions were associated with having a DTI in the univariate analysis. While this therapeutic class is of particular interest in patients with overweight or cardiovascular T2DM, the risk of worsening undernutrition or sarcopenia is too high in cancer patients to justify its use.\u003c/p\u003e \u003cp\u003eFurthermore, although CKD was not present in the logistic model, it is important to highlight that several prescriptions were not adapted to renal function and did not respect contraindications in persons with severe CKD in our study (\u0026sim;10% of DTI), notably regarding metformin, but also sulfonylureas and DPP4i. This reflects findings from an Italian study [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], which demonstrated that the prescription of metformin and sulfonylureas was very prevalent in older adults with moderate and severe CKD, and that there was a high risk of adverse effects such as lactic acidosis and severe hypoglycaemia.\u003c/p\u003e \u003cp\u003eThe present study has limitations. First, as it a retrospective in nature, certain biases may have arisen due to the presence of missing data and the heterogeneity of the study population. Second, 27.9% of patients had no recent actual HbA1c available, making personalised T2DM management more complex. This can be attributed to the fact that HbA1c is not systematically measured during CGA in our unit, particularly when the patient has already undergone a blood test previously, but without any HbA1c measurement. Third, the treatment data set comprised solely the most recent prescriptions (within the previous three months). Most prescriptions were sourced from GPs, which is consistent with the French DIABASIS survey which found that 93% of patients were registered with GP for diabetes care [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. However, it was not possible to determine whether patients were registered with a diabetologist but had their prescriptions renewed by a GP, or whether they were only registered with a GP for diabetes care.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e This study reveals overly aggressive glycaemic control in our frail older population of patients with comorbid cancer and T2DM, and highlights poor clinical adherence to guidelines in the pharmacological management of T2DM. More specifically, older patients with intermediate or poor health tended to have more aggressive individual HbA1c targets than those recommended and therefore tended to be overtreated. Most of the DTI concerned problems related to the prescription of insulin secretagogues, which are widely not recommended in older adults because of the high risk of hypoglycaemia. This finding highlights the need for physicians to adopt updated practices that facilitate personalised treatment management. With their multidisciplinary teams of geriatricians, dieticians, psychologists, and clinical pharmacists, geriatric day hospitals provide patient-centred care which is essential to detect ageing-related complications. Geriatrician-pharmacist collaborations in these structures lead to a more comprehensive understanding of the patient\u0026rsquo;s profile, which in turn guides therapeutic choices based on individualised glycaemic targets. Moreover, active communication between geriatricians and GPs upon the completion of a CGA would foster more comprehensive implementation of T2DM recommendations in older cancer adults.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOn behalf of all authors, the corresponding author states that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsidering that routinely collected data were anonymised, informed consent was not required.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with French law, approval from an Institutional Review Board was not necessary, as this is a retrospective non-interventional study which reuses existing data. The study\u0026rsquo;s database was registered on the AP-HM\u0026rsquo;s health data access portal under number PADS24-120.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et al. 13. Older Adults: Standards of Care in Diabetes-2023. Diabetes Care 2023;46:S216\u0026ndash;29. https://doi.org/10.2337/dc23-S013.\u003c/li\u003e\n\u003cli\u003eMagliano DJ, Boyko EJ, IDF Diabetes Atlas 10th edition scientific committee. IDF DIABETES ATLAS. 10th ed. Brussels: International Diabetes Federation; 2021.\u003c/li\u003e\n\u003cli\u003eMasnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr 2017;17:230. https://doi.org/10.1186/s12877-017-0621-2.\u003c/li\u003e\n\u003cli\u003eVischer U-M, Bauduceau B, Bourdel-Marchasson I, Blickle J-F, Constans T, Fagot-Campagna A, et al. A call to incorporate the prevention and treatment of geriatric disorders in the management of diabetes in the elderly. Diabetes Metab 2009;35:168\u0026ndash;77. https://doi.org/10.1016/j.diabet.2009.02.003.\u003c/li\u003e\n\u003cli\u003eBradley D, Hsueh W. Type 2 Diabetes in the Elderly: Challenges in a Unique Patient Population. J Geriatr Med Gerontol 2016;2:14. https://doi.org/10.23937/2469-5858/1510014.\u003c/li\u003e\n\u003cli\u003eBonds DE, Miller ME, Bergenstal RM, Buse JB, Byington RP, Cutler JA, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010;340:b4909. https://doi.org/10.1136/bmj.b4909.\u003c/li\u003e\n\u003cli\u003eKhunti K, Davies M, Majeed A, Thorsted BL, Wolden ML, Paul SK. Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study. Diabetes Care 2015;38:316\u0026ndash;22. https://doi.org/10.2337/dc14-0920.\u003c/li\u003e\n\u003cli\u003eHuang ES. Individualizing Care for Older Adults With Diabetes Amid the Revolution in Pharmacotherapy. JAMA Intern Med 2024;184:435. https://doi.org/10.1001/jamainternmed.2023.8559.\u003c/li\u003e\n\u003cli\u003eDoucet J, Verny C, Balkau B, Scheen AJ, Bauduceau B. Haemoglobin A1c and 5-year all-cause mortality in French type 2 diabetic patients aged 70 years and older: The GERODIAB observational cohort. Diabetes \u0026amp; Metabolism 2018;44:465\u0026ndash;72. https://doi.org/10.1016/j.diabet.2018.05.003.\u003c/li\u003e\n\u003cli\u003eDarmon P, Bauduceau B, Bordier L, Detournay B, Gourdy P, Guerci B, et al. Prise de position de la Soci\u0026eacute;t\u0026eacute; Francophone du Diab\u0026egrave;te (SFD) sur les strat\u0026eacute;gies d\u0026rsquo;utilisation des traitements anti-hyperglyc\u0026eacute;miants dans le diab\u0026egrave;te de type 2 \u0026ndash; 2021. M\u0026eacute;decine Des Maladies M\u0026eacute;taboliques 2021;15:781\u0026ndash;801. https://doi.org/10.1016/j.mmm.2021.10.014.\u003c/li\u003e\n\u003cli\u003eDavies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022;45:2753\u0026ndash;86. https://doi.org/10.2337/dci22-0034.\u003c/li\u003e\n\u003cli\u003eLega IC, Campitelli MA, Austin PC, Na Y, Zahedi A, Leung F, et al. Potential diabetes overtreatment and risk of adverse events among older adults in Ontario: a population-based study. Diabetologia 2021;64:1093\u0026ndash;102. https://doi.org/10.1007/s00125-020-05370-7.\u003c/li\u003e\n\u003cli\u003eDoucet J, Gu\u0026eacute;rin O, Hilbert C, Bordier L, Verny C, Marchand C, et al. Changes in antidiabetic drug prescription patterns during follow-up of the GERODIAB cohort. Comparison with professional recommendations. Diabetes Epidemiology and Management 2023;9:100084. https://doi.org/10.1016/j.deman.2022.100084.\u003c/li\u003e\n\u003cli\u003eMohile SG, Dale W, Somerfield MR, Schonberg MA, Boyd CM, Burhenn PS, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. J Clin Oncol 2018;36:2326\u0026ndash;47. https://doi.org/10.1200/JCO.2018.78.8687.\u003c/li\u003e\n\u003cli\u003eScott\u0026eacute; F, Bossi P, Carola E, Cudennec T, Dielenseger P, Gomes F, et al. Addressing the quality of life needs of older patients with cancer: a SIOG consensus paper and practical guide. Ann Oncol 2018;29:1718\u0026ndash;26. https://doi.org/10.1093/annonc/mdy228.\u003c/li\u003e\n\u003cli\u003eLoh KP, Liposits G, Arora SP, Neuendorff NR, Gomes F, Krok-Schoen JL, et al. Adequate assessment yields appropriate care\u0026mdash;the role of geriatric assessment and management in older adults with cancer: a position paper from the ESMO/SIOG Cancer in the Elderly Working Group. ESMO Open 2024;9:103657. https://doi.org/10.1016/j.esmoop.2024.103657.\u003c/li\u003e\n\u003cli\u003eCouderc A-L, Boisseranc C, Rey D, Nouguerede E, Greillier L, Barlesi F, et al. Medication Reconciliation Associated with Comprehensive Geriatric Assessment in Older Patients with Cancer: ChimioAge Study. CIA 2020;15:1587\u0026ndash;98. https://doi.org/10.2147/CIA.S262209.\u003c/li\u003e\n\u003cli\u003eSoubeyran P, Bellera C, Goyard J, Heitz D, Cur\u0026eacute; H, Rousselot H, et al. Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study. PLoS One 2014;9:e115060. https://doi.org/10.1371/journal.pone.0115060.\u003c/li\u003e\n\u003cli\u003eFolstein MF, Folstein SE, McHugh PR. \u0026ldquo;Mini-mental state\u0026rdquo;. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189\u0026ndash;98. https://doi.org/10.1016/0022-3956(75)90026-6.\u003c/li\u003e\n\u003cli\u003eKatz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. the index of ADL: a standardized measure of biological and psychosocial function. JAMA 1963;185:914\u0026ndash;9. https://doi.org/10.1001/jama.1963.03060120024016.\u003c/li\u003e\n\u003cli\u003eLawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179\u0026ndash;86.\u003c/li\u003e\n\u003cli\u003eHaute Autorite ́ de Sante ́ (HAS) Diagnostic de la d\u0026eacute;nutrition chez la personne de 70 ans et plus [https://www.has-sante.fr/upload/docs/application/pdf/2021-11/reco368_recommandations_denutrition_pa_cd_20211110_v1.pdf (Accessed August)] n.d.\u003c/li\u003e\n\u003cli\u003eMagnuson A, Sattar S, Nightingale G, Saracino R, Skonecki E, Trevino KM. A Practical Guide to Geriatric Syndromes in Older Adults With Cancer: A Focus on Falls, Cognition, Polypharmacy, and Depression. Am Soc Clin Oncol Educ Book 2019;39:e96\u0026ndash;109. https://doi.org/10.1200/EDBK_237641.\u003c/li\u003e\n\u003cli\u003eMohile SG, Fan L, Reeve E, Jean-Pierre P, Mustian K, Peppone L, et al. Association of cancer with geriatric syndromes in older Medicare beneficiaries. J Clin Oncol 2011;29:1458\u0026ndash;64. https://doi.org/10.1200/JCO.2010.31.6695.\u003c/li\u003e\n\u003cli\u003eHandforth C, Clegg A, Young C, Simpkins S, Seymour MT, Selby PJ, et al. The prevalence and outcomes of frailty in older cancer patients: a systematic review. Ann Oncol 2015;26:1091\u0026ndash;101. https://doi.org/10.1093/annonc/mdu540.\u003c/li\u003e\n\u003cli\u003eBaretella O, Alwan H, Feller M, Aubert CE, Del Giovane C, Papazoglou D, et al. Overtreatment and associated risk factors among multimorbid older patients with diabetes. Journal of the American Geriatrics Society 2023;71:2893\u0026ndash;901. https://doi.org/10.1111/jgs.18465.\u003c/li\u003e\n\u003cli\u003eDoucet J, Le Floch J-P, Bauduceau B, Verny C, SFD/SFGG Intergroup. GERODIAB: Glycaemic control and 5-year morbidity/mortality of type 2 diabetic patients aged 70 years and older: 1. Description of the population at inclusion. Diabetes Metab 2012;38:523\u0026ndash;30. https://doi.org/10.1016/j.diabet.2012.07.001.\u003c/li\u003e\n\u003cli\u003eParis J, Legris P, Devaux M, Bost S, Gueneau P, Rossi C, et al. Impact of a Tripartite Collaboration between Oncologist, Pharmacist and Diabetologist in the Management of Patients with Diabetes Starting Chemotherapy: The ONCODIAB Trial. Cancers 2023;15:4544. https://doi.org/10.3390/cancers15184544.\u003c/li\u003e\n\u003cli\u003ePilla SJ, Jalalzai R, Tang O, Schoenborn NL, Boyd CM, Golden SH, et al. A National Physician Survey of Deintensifying Diabetes Medications for Older Adults With Type 2 Diabetes. Diabetes Care 2023;46:1164\u0026ndash;8. https://doi.org/10.2337/dc22-2146.\u003c/li\u003e\n\u003cli\u003eDoucet J, Gourdy P, Meyer L, Benabdelmoumene N, Bourdel-Marchasson I. Management of Glucose-Lowering Therapy in Older Adults with Type 2 Diabetes: Challenges and Opportunities. CIA 2023;Volume 18:1687\u0026ndash;703. https://doi.org/10.2147/CIA.S423122.\u003c/li\u003e\n\u003cli\u003eBauduceau B, Bordier L, Doucet J. Interest and place of new therapeutic classes in the treatment of elderly diabetic patients. Diabetes Metab 2023;49:101431. https://doi.org/10.1016/j.diabet.2023.101431.\u003c/li\u003e\n\u003cli\u003eStrain WD, Hope SV, Green A, Kar P, Valabhji J, Sinclair AJ. Type 2 diabetes mellitus in older people: a brief statement of key principles of modern day management including the assessment of frailty. A national collaborative stakeholder initiative. Diabet Med 2018;35:838\u0026ndash;45. https://doi.org/10.1111/dme.13644.\u003c/li\u003e\n\u003cli\u003eRemelli F, Ceresini MG, Trevisan C, Noale M, Volpato S. Prevalence and impact of polypharmacy in older patients with type 2 diabetes. Aging Clin Exp Res 2022;34:1969\u0026ndash;83. https://doi.org/10.1007/s40520-022-02165-1.\u003c/li\u003e\n\u003cli\u003eSinclair AJ, Girling AJ, Bayer AJ. Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. Diabetes Research and Clinical Practice 2000;50:203\u0026ndash;12. https://doi.org/10.1016/S0168-8227(00)00195-9.\u003c/li\u003e\n\u003cli\u003eLipska KJ, Krumholz H, Soones T, Lee SJ. Polypharmacy in the Aging Patient. JAMA 2016;315:1034\u0026ndash;45. https://doi.org/10.1001/jama.2016.0299.\u003c/li\u003e\n\u003cli\u003eFreeman J. Management of hypoglycemia in older adults with type 2 diabetes. Postgrad Med 2019;131:241\u0026ndash;50. https://doi.org/10.1080/00325481.2019.1578590.\u003c/li\u003e\n\u003cli\u003eSolini A, Penno G, Bonora E, Fondelli C, Orsi E, Trevisan R, et al. Age, renal dysfunction, cardiovascular disease, and antihyperglycemic treatment in type 2 diabetes mellitus: findings from the Renal Insufficiency and Cardiovascular Events Italian Multicenter Study. J Am Geriatr Soc 2013;61:1253\u0026ndash;61. https://doi.org/10.1111/jgs.12381.\u003c/li\u003e\n\u003cli\u003eMosnier-Pudar H, Hochberg G, Eschwege E, Virally M-L, Halimi S, Guillausseau PJ, et al. How do patients with type 2 diabetes perceive their disease? Insights from the French DIABASIS survey. Diabetes Metab 2009;35:220\u0026ndash;7. https://doi.org/10.1016/j.diabet.2009.02.001.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Diabetes, Older cancer adults, Geriatrician-pharmacist collaboration, Pharmaceutical care, Therapeutic management","lastPublishedDoi":"10.21203/rs.3.rs-5349587/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5349587/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e:\u003c/strong\u003e Substantial clinical heterogeneity in older adults with diabetes makes therapeutic management challenging. This study compared real-world type 2 diabetes management of older outpatients who had comorbid cancer with published guidelines in order to identify the circumstances in which antidiabetic treatment de-intensification might be appropriate.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e:\u003c/strong\u003e We retrospectively analysed data from comprehensive geriatric assessment-guided medication reviews of all outpatients with comorbid diabetes referred to our geriatric oncology day hospital unit in 2022-2023.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e:\u003c/strong\u003e Of the 738 outpatients who had a medication review, 190 had comorbid diabetes; mean age was 79.5 ± 5.6 years. Despite the high prevalence of frailties and geriatric syndromes observed, the mean HbA1c level was low (6.89% ± 1.03%). Two-thirds (63.5%) of participants had an HbA1c outside the recommended individual target range. Of these, 80% had an HbA1c below the range, suggesting overtreatment. Sulfonylureas and glinides accounted for 18.4% and 11.6% of antidiabetic prescriptions, respectively. A total of 170 diabetes-related therapeutic issues were identified in 67.9% of patients. Having an HbA1c below the individual target range (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) and receiving at least three prescribed antidiabetic drugs (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.05) were both significantly associated with having at least one diabetes-related therapeutic issue.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e: \u003c/strong\u003eOur study revealed overly aggressive glycaemic control in this frail older population of patients with comorbid cancer and diabetes and highlights poor clinical adherence to official guidelines. Geriatrician-pharmacist collaborations could provide a more comprehensive understanding of patients’ health status and functional category profiles and improve the therapeutic management of older patients with diabetes.\u003c/p\u003e","manuscriptTitle":"Comparing real-world Type 2 diabetes management with the Francophone Diabetes Society’s recommendations: using comprehensive geriatric assessment-guided medication reviews of frail older adults living with comorbid diabetes and cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-21 13:04:52","doi":"10.21203/rs.3.rs-5349587/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7dc081ed-0e69-4693-8cce-42326aceee92","owner":[],"postedDate":"November 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-27T10:01:29+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-21 13:04:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5349587","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5349587","identity":"rs-5349587","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}