Effects of Exenatide Plus Rosiglitazone on Beta Cell Function and Insulin Sensitivity in Subjects with Type 2 Diabetes on Metformin

Therapy with exenatide plus rosiglitazone offset the weight gain observed with rosiglitazone, and elicited an additive effect on glycemic control, with significant improvements, researchers from the Department of Medicine, University of Texas Health Science Center, San Antonio, TX found in a new study….

The object of the study was to measure 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.

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 mug twice daily (BID) (n = 45), ROSI 4 mg BID (n = 45), or EXE 10 mug BID + ROSI 4 mg BID (n = 47). Seventy-three participants underwent clamp procedures to quantitate insulin secretion and insulin sensitivity.

The results showed 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). 

From the results it was concluded that 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.