SGLT2 inhibitor versus carbohydrate-restricted isocaloric diet: Reprogramming oxidation in type 2 diabetes

Abstract Objective: This study aimed to determine whether the carbohydrate-restricted isocaloric (CRIC) diet and sodium/glucose cotransporter-2 inhibitor (SGLT2i) differed with respect to the fasting and postprandial energy expenditure (EE) and macronutrient oxidation, and insulin dose required to achieve euglycemia. Methods: This randomized 3-arm open-label prospective study enrolled 23 patients with type 2 diabetes (male/female: 14/9, age: 53.6±14.2 years, body mass index: 26.9±4.8 kg/m2, HbA1c: 12.5±1.6%) treated with titrated basal-bolus insulin subsequent to the control diet (CON) alone, administration of canagliflozin 100 mg/day (SGLT2i) to the CON, or CRIC diet for 12 weeks. The main outcome measures included the fasting and postprandial EE, respiratory quotient (RQ), and required dose of insulin. Results: Although the fasting EE was similar in all groups, postprandial EE was significantly elevated in the SGLT2i and CRIC groups compared to the CON group (p=0.03 and 0.04). The fasting RQ was lower in the SGLT2i group (p=0.049) and delta-RQ (postprandial RQ/fasting RQ) was elevated due to increased carbohydrate substrate utilization in the SGLT2i (p=0.04) and CRIC (p=0.03) groups compared to the CON group. The total required daily dose of insulin was significantly higher in the CRIC (p=0.02) group, although the amount of available carbohydrate was similar in the CRIC and SGLT2i groups. Conclusion: The CRIC diet resulted in a similar fasting and postprandial EE and substrate oxidation compared to SGLT2i. The increased insulin requirement in the CRIC diet indicates that a relatively high lipid and protein ratio (compared to the SGLT2i and CON) may influence insulin requirement.