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 super(1,2)

Diabet. Med. 27, 556-562 (2010) Aims 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 Type2 diabetes inadequately controlled on metformin alone. Methods In this double-blind phaseII trial, subjects were randomized to placebo or taspoglutide (20mg; three separate groups) administered once weekly by subcutaneous injection for 4weeks. This was followed by dose maintenance at 20mg, or titration to 30mg (20/30) or 40mg (20/40) once weekly with matched placebo for an additional 4weeks. Subjects were monitored for adverse events (AEs) throughout the study and 4-week follow-up. Results One hundred and twenty-nine subjects were randomized and treated [mean age 57years, mean baseline glycated haemoglobin (HbA sub(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 20mg 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 Three subjects were withdrawn from the study as a result of gastrointestinal AEs (one before and two after titration to higher doses).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 sub(1c)