Dipeptidyl peptidase-4 inhibitors associated heart failure events in adult patients with type-2 diabetes mellitus treated with dipeptidyl peptidase-4 inhibitors: A systematic review and meta-analysis

Dipeptidyl peptidase-4 inhibitors associated heart failure events in adult patients with type-2 diabetes mellitus treated with dipeptidyl peptidase-4 inhibitors: A systematic review and meta-analysis | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 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Data may be preliminary. 6 March 2026 V1 Latest version Share on Dipeptidyl peptidase-4 inhibitors associated heart failure events in adult patients with type-2 diabetes mellitus treated with dipeptidyl peptidase-4 inhibitors: A systematic review and meta-analysis Authors : Shishir Nepal 0009-0009-0280-1411 [email protected] and Shiva Prasad Nepal 0009-0001-4022-3271 Authors Info & Affiliations https://doi.org/10.22541/au.177277876.64974372/v1 377 views 52 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: DPP-4 inhibitors use has been reported to cause heart failure events in patients with type-2 diabetes. The FDA had also issued warnings concerning increased risk of heart failure events for alogliptin, saxagliptin and their combination with metformin. Methods: Randomized controlled trials (RCTs) involving adult patients with type-2 diabetes patients with or without history of cardio-vascular disorders were included in the review. Cohort studies, case-control studies and other non-RCTs, and studies involving pediatric patients were excluded. Data bases searched were PubMed/Medline, DOAJ, MDPI, Google scholar, and clinicaltrails.gov. The search was conducted in February of 2026. Risk of bias was assessed using RoB-2 tool for RCTs. Individual study outcomes were tabulated and summary measure was synthesized by meta-analysis under random effect model; systematic review was done under PRISMA 2020 Guidelines. Results: The meta-analysis was done under random effect computation model for all 29 included studies. The analysis for total of pooled 67,873 patients showed no statistically significant association between the use of Dipeptidyl peptidase-4 inhibitors and heart failure risk (Log Risk Ratio (RR) = 0.0573, Standard Error (S.E) = 0.0608, Z = 0.942, p = 0.345). The risk ratio as summary effect of the meta-analysis corresponds to 1.06 (95%, C.I [-0.939 to 1.192]). Conclusion: Since our meta-analysis found statistically insignificant finding and TOST test was significant within ±0.223 log risk ratio, the implication of this analysis lies in the fact that change in clinical decision regarding normal and regular oral anti-diabetic regimen involving DPP-4 Inhibitor is not necessary. Supplementary Material File (figure no. 1 prisma flow diagram.docx) Download 46.71 KB File (manuscript dpp-4.docx) Download 473.02 KB File (table no. 1 study chracteristics.docx) Download 33.43 KB File (table no. 2 outcomes of each studies.docx) Download 19.98 KB Information & Authors Information Version history V1 Version 1 06 March 2026 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Shishir Nepal 0009-0009-0280-1411 [email protected] Pokhara Academy of Health Sciences View all articles by this author Shiva Prasad Nepal 0009-0001-4022-3271 Tribhuvan University Faculty of Management View all articles by this author Metrics & Citations Metrics Article Usage 377 views 52 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Shishir Nepal, Shiva Prasad Nepal. Dipeptidyl peptidase-4 inhibitors associated heart failure events in adult patients with type-2 diabetes mellitus treated with dipeptidyl peptidase-4 inhibitors: A systematic review and meta-analysis. Authorea . 06 March 2026. DOI: https://doi.org/10.22541/au.177277876.64974372/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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