In a randomized, double-blind, Phase III trial in patients with T2DM, the sodium glucose cotransporter 2 inhibitor empagliflozin (EMPA) 25 mg qd as add-on to metformin for 104 weeks led to significant and sustained reductions in body weight compared with an increase in body weight with glimepiride (GLIM).  Patients could participate in a dedicated body composition sub-study.  Using whole body dual energy X-ray absorptiometry, fat, limb fat, total fat mass and fat-free mass were assessed (62 patients; 36 EMPA, 26 GLIM).  Using magnetic resonance imaging, abdominal visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) were assessed (51 patients; 29 EMPA, 22 GLIM).  Changes from baseline were evaluated using mixed model repeated measures (MMRM) analyses.  In the sub-study (N = 91), baseline mean (standard deviation) age was 55.7 (10.4) years, weight was 85.1 (14.7) kg, body mass index (BMI) was 31.9 (4.9) kg/m² and 60% had BMI ≥30 kg/m².  EMPA significantly reduced trunk fat, limb fat and total fat mass vs GLIM at week 52 and week 104, and fat-free mass vs GLIM at week 52 but not at week 104 (Table).  Adjusted mean (SE) changes from baseline in abdominal VAT: at week 52, -15.5 (5.2) cm² EMPA, +10.0 (6.1) cm² GLIM (p<0.01); at week 104, ‑16.0 (8.4) cm² EMPA, +17.7 (10.0) cm² GLIM (p<0.05).  Adjusted mean (SE) changes from baseline in abdominal SAT: week 52, ‑29.9 (7.3) cm² EMPA, +25.8 (8.6) cm² GLIM (p<0.001); at week 104, ‑32.5 (9.2) cm² EMPA, +34.4 (10.7) cm² GLIM (p<0.001).  When used as add-on to metformin, treatment with EMPA led to reductions in trunk fat, limb fat, abdominal VAT and SAT at week 52, and further reductions at week 104, compared with GLIM.  Reductions in fat-free mass with EMPA versus GLIM were observed at week 52, but not at week 104.  

This study was sponsored by Boehringer Ingelheim.