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

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.The well-known limitations of insulin therapy are weight gain and increased risk of hypoglycemia (1,2). Results of cardiovascular outcome trials (3,4) have triggered a discussion about the association between hypoglycemia and increased mortality (5). The American Diabetes Association defines the prevention of hypoglycemia as a critical component of diabetes management (6). This study was specifically designed to compare hypoglycemia with exenatide twice daily (BID) versus premixed insulin aspart 70/30 BID (PIA) (70% protamin crystallized, 30% soluble) at a noninferior level of glycemic control in type 2 diabetic patients on metformin treatment. An additional smaller patient cohort previously treated with metformin plus sulfonylurea or meglitinides was enrolled into an exploratory arm; data have been published separately (7).