Exenatide twice daily versus premixed insulin aspart 70/30 in metformin-treated patients with type 2 diabetes: a randomized 26-week study on glycemic control and hypoglycemia

Abstract

Objective: Hypoglycemia causes recurrent morbidity in patients with type 2 diabetes. This study evaluated if exenatide twice daily (BID) was noninferior to premixed insulin aspart 70/30 BID (PIA) for glycemic control and associated with less hypoglycemia.

Research design and methods: In this open-label study, metformin-treated adults with type 2 diabetes were randomized to 26-week treatment with exenatide BID (4 weeks 5 μg, then 10 μg) or PIA.

Results: Exenatide BID (n = 181) was noninferior to PIA (n = 173) for A1C control (least squares [LS] mean change -1.0 vs. -1.14%; difference [95% CI] 0.14 [-0.003 to 0.291]) and associated with a lower risk for hypoglycemia (8.0 vs. 20.5%, P < 0.05). LS mean weight decreased by 4.1 kg and increased by 1.0 kg with PIA (P < 0.001). A total of 39.2 vs. 20.8% of patients reached the composite end point of A1C <7.0%, no weight gain, and no hypoglycemia (P < 0.001; post hoc analysis).

Conclusions: In metformin-treated patients, exenatide BID was noninferior to PIA for glycemic control but superior for hypoglycemia and weight control.

Trial registration: ClinicalTrials.gov NCT00434954.

Figures

Figure 1

LS mean change in A1C (A) and risk of hypoglycemic episodes (B) up to week 26 (full analysis set, all patients treated). A: Data were derived from an MMRM analysis, adjusting for baseline A1C. B: *P < 0.05 for second step of hierarchical testing procedure. The risk for the first hypoglycemic episode (blood glucose [BG] ≤3.9 mmol/L or severe, but no severe observed) to occur up to week 26 was tested for superiority of exenatide (EXE) BID over PIA by nonoverlapping 95% CIs from Kaplan-Meier analysis (two-sided, α = 0.05). Vertical bars indicate 95% CIs.