Efficacy and Safety of Taspoglutide Versus Sitagliptin for Type 2 Diabetes Mellitus (T-Emerge 4 Trial)

INTRODUCTION: The 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. METHODS: In 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 (HbA(1c)) after 24 weeks. RESULTS: In this study, 666 patients (baseline HbA(1c), 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) HbA(1c) 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 HbA(1c) 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. CONCLUSION: Taspoglutide 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

Effect on Weight Loss of an Oral Supplement Containing Cinnamon Bark (<i>Cinnamomum cassia</i>) and <i>Withania somnifera</i> in Adult Patients with Overweight and Obesity: A Pilot Study

With the prevalence of obesity soaring and the absence of an effective and safe treatment that is low-cost and always feasible, food supplements have gained attention for their potential benefits in the absence of significant safety concerns. Cinnamomum cassia (CC) and Withania somnifera (WS) are plant-based supplements reported to be effective in improving metabolic health and body composition, the first mainly acting on insulin resistance and the second on energy expenditure and leptin resistance, as shown in preclinical and some clinical studies. Their combination, which is possibly synergistic given their different mechanisms of action, has never been studied. This was a double-blind placebo-controlled study. Patients with overweight or obesity were prescribed a mildly hypocaloric diet with 300 mg CC plus 150 mg WS tid for 4 weeks in a crossover design; anthropometric parameters and safety outcomes were collected. Forty patients were enrolled, and the combination CC + WS induced significant weight loss compared with placebo (−2.66% vs. −1.28%, respectively; p = 0.0002). No significant adverse events were recorded. Our study demonstrates for the first time that the tested combination is an inexpensive yet effective strategy to enhance weight loss in patients receiving a mildly hypocaloric diet. Further studies are warranted to investigate the mechanisms underlying the weight loss effect of CC/WS in human subjects, as well as to explore potential additional metabolic effects obtained with this treatment