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Aim To assess the efficacy, safety and tolerability of beloranib treatment for obesity. Methods This phase II, double-blind, randomized study investigated the effects of beloranib suspension (0.6, 1.2 and 2.4 mg) or placebo, administered subcutaneously, for 12 weeks in 147 participants (primarily white women) with obesity. No diet or exercise advice was administered. Results At week 12, beloranib resulted in dose-dependent progressive weight loss of −5.5 ± 0.5, −6.9 ± 0.6 and −10.9 ± 1.1 kg for the 0.6, 1.2 and 2.4 mg beloranib doses, respectively, compared with −0.4 ± 0.4 kg with placebo (all p < 0.0001 vs placebo). Weight loss with beloranib was associated with corresponding reductions in waist circumference and body fat mass, as well as improvements in lipids, high-sensitivity C-reactive protein and blood pressure. Sleep disturbance and gastrointestinal adverse events were more common with beloranib than with placebo; these were generally mild to moderate, transient and dose-related, and led to more early study withdrawals in participants in the group with the highest dose of beloranib. Conclusions In this 12-week phase II study, beloranib produced clinically and statistically significant weight loss and corresponding improvements in cardiometabolic risk factors. Beloranib appeared safe, and the 0.6 and 1.2 mg doses were generally well tolerated. The 2.4 mg dose was associated with increased sleep latency and mild to moderate gastrointestinal adverse events over the first month of treatment. These findings represent a novel mechanism for producing clinically meaningful weight loss. [ABSTRACT FROM AUTHOR]

Aim: Exenatide, an incretin mimetic for the adjunct treatment of type 2 diabetes (DM2), reduced A1C and weight in 30-week placebo-controlled trials. This analysis examined the effects of exenatide on glycaemic control and weight over an 82-week period in patients with DM2 unable to achieve adequate glycaemic control with sulphonylurea (SU) and/or metformin (MET). Methods: This interim analysis is of 314 patients who received exenatide in the 30-week placebo-controlled trials and subsequently in 52 weeks of open-label uncontrolled extension studies for 82 weeks of exenatide in total. Patients continued their SU and/or MET regimens throughout. Results: Patients completed 82 weeks of exenatide treatment [n = 314, 63% M, age 56 ± 10 years, weight 99 ± 21 kg, body mass index 34 ± 6 kg/m2, A1C 8.3 ± 1.0% (mean ± SD)]. Reduction in A1C from baseline to week 30 [−0.9 ± 0.1% (mean ± SE)] was sustained to week 82 (−1.1 ± 0.1%), with 48% of patients achieving A1C ≤ 7% at week 82. At week 30, exenatide reduced body weight (a secondary endpoint) from baseline (−2.1 ± 0.2 kg), with progressive reduction at week 82 (−4.4 ± 0.3 kg). Similar results were observed for the intent-to-treat population (n = 551), with reductions in A1C and weight at week 82 of −0.8 ± 0.1% and −3.5 ± 0.2 kg respectively. The 82-week completer cohort showed statistically significant improvement in some cardiovascular risk factors. The most frequent adverse events were generally mild-to-moderate nausea and hypoglycaemia. Conclusion: In summary, 82 weeks of adjunctive exenatide treatment in patients with DM2 treated with SU and/or MET resulted in sustained reduction in A1C and progressive reduction in weight, as well as improvement in some cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Aim: The ability of the incretin mimetic exenatide to improve glycaemic control and reduce body weight was assessed over 82 weeks in patients with type 2 diabetes failing to achieve glycaemic control with maximally effective doses of metformin. Methods: In this interim 82-week analysis, 150 (total cohort) of an eligible population of 183 patients opted to continue exenatide treatment in an uncontrolled open-label extension of a 30-week double-blind, placebo-controlled trial. Of these, 92 patients (completer cohort) achieved 82 weeks of exenatide therapy. Patients continued metformin throughout the study. Results: At the end of the placebo-controlled trial, exenatide resulted in an haemoglobin A1c (HbA1c) reduction from baseline of −1.0 ± 0.1% (mean ± SE) (exenatide treatment arms), with durable HbA1c reductions after 82 weeks of −1.3 ± 0.1%. The percent of patients who achieved HbA1c≤7% at weeks 30 and 82 was 46 and 59% respectively. After 30 weeks, exenatide caused a reduction in weight from baseline of −3.0 ± 0.6 kg, with a progressive reduction in weight of −5.3 ± 0.8 kg after 82 weeks. In addition, exenatide treatment produced clinically significant improvements in cardiovascular risk factors after 82 weeks. The most frequent adverse event after 30 and 82 weeks of exenatide was nausea, which was generally of mild-or-moderate intensity. It decreased in incidence after initiation in the controlled trial and the uncontrolled open-label extension. Hypoglycaemia was rare, with no severe events. Conclusion: Exenatide was generally well tolerated, producing a durable reduction in HbA1c and a progressive reduction in weight over 82 weeks in patients with type 2 diabetes failing to achieve glycaemic control with metformin. [ABSTRACT FROM AUTHOR]