Efficacy and Safety of Taspoglutide in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Plus Pioglitazone over 24 Weeks: T-Emerge 3 Trial

Abstract

Objective: This study assessed the efficacy and safety of once-weekly taspoglutide in patients with type 2 diabetes mellitus inadequately controlled with metformin plus pioglitazone compared with placebo. Design:In this randomized, double-blind, parallel-group, placebo-controlled trial (T-emerge 3), 326 patients were randomized to once-weekly sc injections of taspoglutide 10 mg, taspoglutide 20 mg (10 mg for first 4 wk), or placebo. The primary endpoint was change from baseline in glycosylated hemoglobin (HbA1c) at 24 wk.Results: A significant reduction in HbA1c was observed with taspoglutide 10 mg and 20 mg vs. placebo (least square mean Ϫ1.35 and Ϫ1.40% vs. Ϫ0.45%, respectively; P Ͻ 0.0001). A greater proportion of taspoglutide-treated patients reached HbA1c target 7% or less (69.8 and 76.1% vs. 35.1%). With taspoglutide 10 mg and 20 mg vs. placebo, significantly greater reductions in fasting plasma glucose [Ϫ1.87 mmol/liter (Ϫ34 mg/dl) and Ϫ2.12 mmol/liter (Ϫ38 mg/dl) vs. Ϫ0.57 mmol/ liter (Ϫ10 mg/dl); P Ͻ 0.0001], improvements in homeostasis model assessment of ␤-cell function score (20.65 and 33.52 vs. Ϫ2.03; P Ͻ 0.0001), and significant weight loss (Ϫ0.64 kg and Ϫ1.04 kg vs. 0.59 kg; P Ͻ 0.01) were observed. Adverse events were generally mild to moderate; the most frequent adverse events with taspoglutide 10 mg, taspoglutide 20 mg, and placebo were nausea (35, 44, and 10%), vomiting (21, 24, and 2%), and injection site reactions (24, 24, and 5%). Conclusions:Taspoglutide provided glycemic control with weight loss as add-on therapy to metformin plus pioglitazone for inadequately controlled type 2 diabetes mellitus. (J Clin Endocrinol Metab 97: 2370 -2379, 2012)

Effect of GLP-1 receptor agonists on waist circumference among type 2 diabetes patients: a systematic review and network meta-analysis

“…The beneficial waist circumference reduction effect associated with GLP-1RAs observed in our analysis was consistent with relevant trials [36,37,42,43]. A study in 299 T2DM patients showed a significant decrease in waist circumference associated with exenatide accompanied by significant weight loss [42].…”

“…Another trial in 69 T2DM patients demonstrated the significant reduction of waist circumference in exenatide treatment for 1 year [43]. Several trials indicated significant decrease in waist/hip ratio associated with GLP-1RAs [28,32,37]. Modest reduction in waist circumference has been proved to be clinically meaningful for T2DM patients [13,14].…”

The placebo response of injectable GLP‐1 receptor agonists vs. oral DPP‐4 inhibitors and SGLT‐2 inhibitors: a systematic review and meta‐analysis

“…After excluding duplicates and screening references on the basis of title and abstract, 123 relevant references were identified and examined in full text. Sixty‐seven of these publications fulfilled the inclusion criteria and were included in the analysis .…”

“…Of the 67 included RCTs, 18 investigated the efficacy of GLP‐1ra (six examined exenatide , three liraglutide , five lixisenatide , one dulaglutide and three taspoglutide ), 34 examined DPP‐4i (eight sitagliptin , 10 vildagliptin , seven saxagliptin , four alogliptin , five linagliptin ) and 15 researched SGLT‐2i (eight dapagliflozin , four canagliflozin , three empagliflozin ). All included trials were published in English.…”

Comparative efficacy and safety of antidiabetic drug regimens added to stable and inadequate metformin and thiazolidinedione therapy in type 2 diabetes

“…Of the 11 RCTs included, none proved to have a low risk of bias for all seven domains (Figure S3). Four studies demonstrated uncertainty regarding random sequence generation and two studies were unclear in methods of allocation concealment . One study was open‐label and one did not specify the manner of blinding participants and personnel .…”