Treatment with the human once-weekly GLP-1 analogue taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes mellitus inadequately controlled with metformin alone: a double-blind placebo-controlled study

Abstract

Objective: To evaluate the efficacy and safety of taspoglutide (R1583/BIM51077), a human once-weekly glucagon-like peptide-1 analogue, in patients with type 2 diabetes mellitus inadequately controlled with metformin.

Research Design and Methods: Type 2 diabetic (n=306) patients who failed to obtain glycemic control (HbA1c 7-9.5%) despite metformin 1500 mg daily, were randomized to 8 weeks of double-blind subcutaneous treatment with placebo or taspoglutide, either 5, 10, or 20 mg once weekly (QW) or 10 or 20 mg once every 2 weeks (Q2W), and followed for 4 additional weeks. All patients received their previously established dose of metformin throughout the study. Glycemic control was assessed by change in HbA1c (%) from baseline.

Results: Significantly greater (p<0.0001) reductions in HbA1c from a mean baseline of 7.9 ± 0.7% were observed in all taspoglutide groups compared with placebo after 8 weeks of treatment: -1.0±0.1% (5 mg QW), -1.2±0.1% (10 mg QW), -1.2±0.1% (20 mg QW), -0.9±0.1% (10 mg Q2W), -1.0±0.1% (20 mg Q2W), vs. -0.2±0.1% with placebo. After 8 weeks, body weight loss was significantly greater in the 10 mg (-2.1±0.3 kg, p=0.0035 vs. placebo) and 20 mg (-2.8±0.3 kg, p<0.0001) QW groups and the 20 mg Q2W (-1.9±0.3 kg, p=0.0083) arm than with placebo (-0.8±0.3 kg). The most common adverse event was dose-dependent, transient, mild-to-moderate nausea; the incidence of hypoglycemia was very low.

Conclusions: Taspoglutide used in combination with metformin significantly improves fasting and postprandial glucose control and induces weight loss, with a favorable tolerability profile.