Abstract
IntroductionThe efficacy and safety of taspoglutide, a long-acting human glucagon-like peptide-1 analog, were compared with sitagliptin or placebo, as adjunct to metformin, in patients with inadequately controlled type 2 diabetes.MethodsIn this randomized, double-blind, double-dummy, parallel-group trial, patients were randomized to taspoglutide 10 mg once weekly (QW), 20 mg QW, 100 mg sitagliptin once daily (QD), or placebo for 24 weeks, followed by 28-week short-term and 104-week long-term extension periods. The primary endpoint was change in glycosylated hemoglobin (HbA1c) after 24 weeks.ResultsIn this study, 666 patients (baseline HbA1c, 7.96% [SD, 0.87]; fasting plasma glucose, 9.61 mmol/L [2.56]; body weight, 92.4 kg [19.3]) were randomized to taspoglutide 10 mg QW (n = 190), 20 mg QW (n = 198), 100 mg sitagliptin QD (n = 185), or placebo (n = 93) for 24 weeks. After 24 weeks, least squares mean (SE) HbA1c reductions were greater with taspoglutide 10 mg (−1.23% [0.06]) and 20 mg (−1.30% [0.06]) versus sitagliptin (−0.89% [0.06]) or placebo (−0.10% [0.08]). Mean treatment differences with taspoglutide 10 mg and 20 mg were −0.34 (95% confidence intervals [CI]: −0.49, −0.19) and −0.41 (−0.56, −0.26) versus sitagliptin; and −1.13 (−1.31, −0.95) and −1.20 (−1.38, −1.02) versus placebo. Weight loss was greater with taspoglutide 10 mg (−1.8 kg [0.3]) and 20 mg (−2.6 kg [0.3]) than sitagliptin (−0.9 kg [0.3]) or placebo (−0.5 kg [0.4]). Effects on HbA1c and weight loss continued through 52 weeks of treatment. No cases of severe hypoglycemia occurred with any active treatment. Gastrointestinal adverse events, and allergic and injection-site reactions were higher in the taspoglutide groups, causing higher discontinuation rates. Anti-taspoglutide antibodies were confirmed in 46% of patients.ConclusionTaspoglutide demonstrated better efficacy on glycemic control and weight loss than sitagliptin, but a high incidence of adverse events led to high discontinuation rates. The safety profile of taspoglutide in this trial was similar to other trials in the clinical program, and led to the discontinuation of dosing.
Highlights
IntroductionNative glucagon-like peptide-1 (GLP-1) regulates the postprandial rise in blood glucose by augmenting insulin release and blunting glucagon secretion, delaying gastric emptying, and improving satiety
The efficacy and safety of taspoglutide, a long-acting human glucagonlike peptide-1 analog, were compared withFor the T-emerge 4 Study Group.Study investigators listed in the Appendix.ClinicalTrials.gov identifier: NCT00754988.A
Premature discontinuation occurred in 21%, 28%, 7%, and 11% of patients receiving taspoglutide 10 mg, taspoglutide 20 mg, sitagliptin 100 mg, or placebo, respectively, most frequently resulting from adverse events (AEs)
Summary
Native GLP-1 regulates the postprandial rise in blood glucose by augmenting insulin release and blunting glucagon secretion, delaying gastric emptying, and improving satiety These effects are shortlived, as the active hormone is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). The most common treatment-emergent adverse events (AEs) observed with GLP-1 receptor agonists are related to gastrointestinal AEs (nausea, vomiting, diarrhea, and upper abdominal pain). These AEs are considered dose-related and typically become less frequent with subsequent dosing over time. Several DPP-4 inhibitors are approved, including sitagliptin, saxagliptin, and linagliptin These QD agents have the advantage of being oral medications, but offer modest glycemic efficacy and have little effect on body weight [9,10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
