Safety and tolerability of high doses of taspoglutide, a once-weekly human GLP-1 analogue, in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study

• Published in: Diabetic medicine 2010-05, Vol.27 (5), p.556-562
• Main Authors: Ratner, R., Nauck, M., Kapitza, C., Asnaghi, V., Boldrin, M., Balena, R.
• Format: Article
• Language: English
• Subjects: clinical studies; Diabetes Mellitus, Type 2 - drug therapy; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; drug treatment; Female; Gastrointestinal Diseases - chemically induced; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide 1 - adverse effects; Glucagon-Like Peptide 1 - analogs & derivatives; Glucagon-Like Peptide 1 - therapeutic use; Glucagon-Like Peptide-1 Receptor; glucagon-like peptide 1; Glycated Hemoglobin A - analysis; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Injections, Subcutaneous; Male; Metformin - therapeutic use; Middle Aged; Nausea - chemically induced; new drugs; Peptides - administration & dosage; Peptides - adverse effects; Peptides - therapeutic use; Receptors, Glucagon - antagonists & inhibitors; Type 2 diabetes; Vomiting - chemically induced
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2010.02990.x

The study objective was to investigate the safety and tolerability of up-titration to high doses of taspoglutide, a once-weekly human glucagon-like peptide-1 analogue, in subjects with Type 2 diabetes inadequately controlled on metformin alone. In this double-blind phase II trial, subjects were randomized to placebo or taspoglutide (20 mg; three separate groups) administered once weekly by subcutaneous injection for 4 weeks. This was followed by dose maintenance at 20 mg, or titration to 30 mg (20/30) or 40 mg (20/40) once weekly with matched placebo for an additional 4 weeks. Subjects were monitored for adverse events (AEs) throughout the study and 4-week follow-up. One hundred and twenty-nine subjects were randomized and treated [mean age 57 years, mean baseline glycated haemoglobin (HbA(1c)), 7.9%]. The most frequently reported AEs were nausea and vomiting. The number of patients reporting gastrointestinal AEs did not increase following titration to higher doses of taspoglutide or when continuing the initial 20 mg regimen. Three subjects were withdrawn from the study as a result of gastrointestinal AEs (one before and two after titration to higher doses). Although not designed to investigate efficacy, improvement in glycaemic control was observed in all active arms of the study. The proportion of subjects achieving HbA(1c) < 7.0% after 8 weeks of treatment was 72, 53 and 70% in the 20/20-, 20/30- and 20/40-mg arms, respectively, vs. 19% for placebo. Taspoglutide was safe, well tolerated at high doses and efficacious for lowering HbA(1c). Up-titration of dose was not associated with a worsening AE profile.