Treatment With the Human Once-Weekly Glucagon-Like Peptide-1 Analog Taspoglutide in Combination With Metformin Improves Glycemic Control and Lowers Body Weight in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Alone: A double-blind placebo-controlled study

OBJECTIVE: To evaluate the efficacy and safety of taspoglutide (R1583/BIM51077), a human once-weekly glucagon-like peptide-1 analog, in patients with type 2 diabetes inadequately controlled with metformin. RESEARCH DESIGN AND METHODS: Type 2 diabetic (n = 306) patients who failed to obtain glycemic control (A1C 7–9.5%) despite 1,500 mg metformin daily were randomly assigned to 8 weeks of double-blind subcutaneous treatment with placebo or taspoglutide, either 5, 10, or 20 mg once weekly or 10 or 20 mg once every 2 weeks, 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 A1C (percent) from baseline. RESULTS: Significantly greater (P < 0.0001) reductions in A1C from a mean ± SD 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 once weekly), –1.2 ± 0.1% (10 mg once weekly), –1.2 ± 0.1% (20 mg once weekly), –0.9 ± 0.1% (10 mg Q2W), and –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) once-weekly groups and the 20 mg once every 2 weeks (–1.9 ± 0.3 kg, P = 0.0083) group 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.