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

• Published in: Diabetes care Vol. 32; no. 7; pp. 1237 - 1243
• Main Authors: Nauck, Michael A, Ratner, Robert E, Kapitza, Christoph, Berria, Rachele, Boldrin, Mark, Balena, Raffaella
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2009
• Subjects: Biological and medical sciences; Complications and side effects; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes therapy; Diabetes. Impaired glucose tolerance; Diabetics; Dosage and administration; Double-Blind Method; Drug Administration Schedule; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gastrointestinal diseases; Glycated Hemoglobin A - drug effects; Glycated Hemoglobin A - metabolism; Heart attacks; Humans; Hyperglycemia; Hypoglycemic agents; Hypoglycemic Agents - therapeutic use; Insulin - therapeutic use; Lipids - blood; Male; Medical sciences; Metabolic diseases; Metabolic disorders; Metformin - therapeutic use; Miscellaneous; Mortality; Original Research; Peptides; Peptides - administration & dosage; Peptides - adverse effects; Peptides - blood; Peptides - therapeutic use; Physical examinations; Postmenopause; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk factors; Rodents; Safety; Sterilization, Reproductive; Type 2 diabetes; Endocrinopathy; Type 2 diabetes; Human; Drug combination; Nutrition; Body weight; Patient; Metabolic diseases; Corporal biometry; Glucagon like peptide 1; Target tissue resistance; Improvement; Hypoglycemic agent; Biguanides; Gastrointestinal hormone; Treatment; Weekly; Analog; Placebo; Double blind study; Insulin resistance; Metformin; Endocrinology; Glycemia
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc08-1961

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.