A randomized controlled trial of two diets enriched with protein or fat in patients with type 2 diabetes treated with dapagliflozin

Sodium-glucose cotranspsorter-2 (SGLT2) inhibitors (SGLT2i) involve loss of skeletal muscle mass, potentially leading to inadequate HbA1c reduction in type 2 diabetes (T2DM), since muscle mass is related to insulin sensitivity. The benefit of protein-enriched diet for improving HbA1c in SGLT2i-treated T2DM patients remains unclear. We conducted a multicenter, double-blind, randomized, controlled, investigator-initiated clinical trial. 130 T2DM patients treated with dapagliflozin (5 mg) were randomized to isoenergic protein-rich formula diet (P-FD) or fat-rich FD (F-FD) (1:1 allocation) to replace one of three meals/day for 24 weeks. Primary outcome was change in HbA1c. Secondary outcomes were changes in serum insulin, body composition and other metabolic parameters. Although HbA1c decreased significantly in both groups [mean (95% confidence interval) − 0.7% (− 0.9 to − 0.5) in P-FD, − 0.6% (− 0.8 to − 0.5) in F-FD], change in HbA1c was not significantly different between the two groups (P = 0.4474). Fasting insulin and body fat mass decreased, while HDL-cholesterol increased significantly in P-FD, and these changes were significantly greater compared with F-FD (all, P < 0.05). In T2DM treated with dapagliflozin, protein-enriched diet does not contribute to HbA1c reduction, although it decreases serum insulin and body fat mass, and increases HDL-cholesterol compared with fat-enriched diet with identical calories and carbohydrate ratio.