Effects of exenatide plus rosiglitazone on β-cell function and insulin sensitivity in subjects with type 2 diabetes on metformin

OBJECTIVE - Study the effects of exenatide (EXE) plus rosiglitazone (ROSI) on β-cell function and insulin sensitivity using hyperglycemic and euglycemic insulin clamp techniques in participants with type 2 diabetes on metformin. RESEARCH DESIGN AND METHODS - In this 20-week, randomized, open-label, multicenter study, participants (mean age, 56±10 years; weight, 93±16 kg; A1C, 7.8±0.7%) continued their metformin regimen and received either EXE 10 μg b.i.d. (n = 45), ROSI 4 mg b.i.d. (n = 45), or EXE 10 μg b.i.d. + ROSI 4 mg b.i.d. (n = 47). Seventy-three participants underwent clamp procedures to quantitate insulin secretion and insulin sensitivity. RESULTS - A1C declined in all groups (P < 0.05), but decreased most with EXE+ROSI (EXE+ROSI, -1.3 ± 0.1%; ROSI, -1.0 ± 0.1%, EXE, -0.9 ± 0.1%; EXE+ROSI vs. EXE or ROSI, P<0.05). ROSI resulted in weight gain, while EXE and EXE+ROSI resulted in weight loss (EXE,-2.8±0.5 kg; EXE+ROSI,-1.2±0.5 kg; ROSI,+1.5±0.5 kg; P<0.05 between and within all groups). At week 20, 1st and 2nd phase insulin secretion was significantly higher in EXE and EXE+ROSI versus ROSI (both P<0.05). Insulin sensitivity (M value) was significantly higher in EXE+ROSI versus EXE (P = 0.014). CONCLUSIONS - Therapy with EXE+ROSI offset the weight gain observed with ROSI and elicited an additive effect on glycemic control with significant improvements in β-cell function and insulin sensitivity.