Abstract

Objective. Study the effects of exenatide (EXE) plus rosiglitazone (ROSI) on beta-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 twice daily (BID) (n = 45), ROSI 4 mg BID (n = 45), or EXE 10 μg BID + ROSI 4 mg BID (n = 47). 73 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, first and second 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).

Conclusion. Therapy with EXE plus ROSI offset the weight gain observed with ROSI, and elicited an additive effect on glycemic control, with significant improvements in beta-cell function and insulin sensitivity.