Taspoglutide

Aims:To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes.Materials and methods:We electronically searched, up to June 3, 2016, published randomized clinical trials lasting between 24 and 32 weeks that compared a GLP-1RA (albiglutide, dulaglutide, twice-daily exenatide and once-weekly exenatide, liraglutide, lixisenatide, semaglutide and taspoglutide) with placebo or another GLP-1RA. Data on cardiometabolic and safety outcomes were analysed using a mixed-treatment comparison meta-analysis.Results:A total of 34 trials (14 464 participants) met the inclusion criteria; no published data for semaglutide were available. Compared with placebo, all GLP-1RAs reduced glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels (reductions ranged from -0.55% and -0.73 mmol/L, respectively, for lixisenatide to -1.21% and -1.97 mmol/L, respectively, for dulaglutide). There were no differences within short-acting (twice-daily exenatide and lixisenatide) or long-acting (albiglutide, dulaglutide, once-weekly exenatide, liraglutide and taspoglutide) groups. Compared with twice-daily exenatide, dulaglutide treatment was associated with the greatest HbA1c and FPG reduction (0.51% and 1.04 mmol/L, respectively), followed by liraglutide (0.45% and 0.93 mmol/L, respectively) and once-weekly exenatide (0.38% and 0.85 mmol/L, respectively); similar reductions were found when these 3 agents were compared with lixisenatide. Compared with placebo, all GLP-1RAs except albiglutide reduced weight and increased the risk of hypoglycaemia and gastrointestinal side effects, and all agents except dulaglutide and taspoglutide reduced systolic blood pressure. When all GLP-1RAs were compared with each other, no clinically meaningful differences were observed in weight loss, blood pressure reduction or hypoglycaemia risk. Albiglutide had the lowest risk of nausea and diarrhoea and once-weekly exenatide the lowest risk of vomiting.Conclusions:The RCTs in the present analysis show that all GLP-1RAs improve glycaemic control, reduce body weight and increase the risk of adverse gastrointestinal symptoms compared with placebo. Although there were no differences when short-acting agents were compared with each other or when long-acting agents were compared with each other, dulaglutide, liraglutide and once-weekly exenatide were superior to twice-daily exenatide and lixisenatide at lowering HbA1c and FPG levels. There were no differences in hypoglycaemia between these 3 agents, whilst once-weekly exenatide had the lowest risk of vomiting. These results, along with patient's preferences and individualized targets, should be considered when selecting a GLP-1RA.

Background:Taspoglutide (R1583/BIM51077) is a new anti diabetic drug from Hoffmann-La Roche. The compound is to be administered as a subcutaneous injection once weekly and is also effective given bi-weekly. It is a long acting 10% formulation of (Aib 8-35) human glucagon-like polypeptide-1 (7 - 36 amides) with 93% homology with the native polypeptide. It activates the glucagon-like polypeptide-1 receptor. Phase III trials are currently in process.Objective:To provide a critical review of taspoglutide based on available published data.Methods:Information provided from the search on Internet has been reviewed. A clinical interpretation is given on a background of practical experience as an investigator in a clinical trial with taspoglutide.Results:Search on PubMed, EMBASE and Google gave hits on six clinical studies investigating taspoglutide of which the largest accounted for > 50% of the total study population. In addition, some animal studies were identified. Significant improvement on glucose control as well as several metabolic parameters has been shown with taspoglutide.Discussion:Data from the clinical trials are interpreted in a medical context. The prospects of taspoglutide in the treatment of diabetes type 2 and metabolic syndrome are discussed.Conclusion:Taspoglutide is a new activator of the glucagon-like polypeptide-1 receptor. It is effective when injected once weekly and less effective when injected bi-weekly. In addition to its anti diabetic properties, taspoglutide has favorable effects on body weight and significantly reduces three of five diagnostic criteria for metabolic syndrome, namely glucose, waist circumference and fasting triglyceride.

Taspoglutide has elicited a long-lasting glycemic control effect with favorable body weight loss. The objective of this study was to develop a quantitative model to delineate the net efficacy of taspoglutide on body weight (WT) loss from the response of placebo in type 2 diabetes patients, and further find pharmacodynamic potency of taspoglutide for half of maximum reduction response of WT. Several PD data about taspoglutide treatments for type 2 diabetes patients were digitalized from the published papers. The model based metaanalysis (MBMA) study for WT loss was performed with Monolix 4.3 software. The MBMA successfully described the effects of placebo and taspoglutide on the pharmacological index of WT loss in clinical trials. The pharmacodynamic potency (41.7 pmol/l) produced 50% of maximum response of WT (-1.85 kg) from the responses of placebo (-1.33 kg). The longitudinal MBMA could be utilized to quantitatively describe the efficacy of taspoglutide on body weight loss and may lead to a clinical guideline for treatment of type 2 diabetes patients in the future.