Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis.
To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes.
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.
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.
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.
Htike ZZ
，Zaccardi F
，Papamargaritis D
，Webb DR
，Khunti K
，Davies MJ
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GLP-1 Receptor Agonists: Practical Considerations for Clinical Practice.
Type 2 diabetes (T2D) imparts an increased risk of adverse health outcomes in patients unable to achieve glycemic control. Patient education and individualization of treatment are important for effective management of T2D. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of injectable glucose-lowering agents that lower A1C with added benefits of weight loss and improved cardiovascular risk markers. This review discusses the role of GLP-1RAs currently approved in the United States (exenatide, liraglutide, albiglutide, dulaglutide) for T2D management and characterizes the efficacy and safety profiles of individual GLP-1RAs.
GLP-1RAs are recommended as a preferred add-on agent to existing metformin monotherapy, as first-line therapy if metformin is contraindicated or poorly tolerated, and for use in combination with other oral glucose-lowering agents or basal insulin. Shorter-acting GLP-1RAs (exenatide and liraglutide) offer improved coverage of postprandial hyperglycemia, while longer-acting GLP-1RA formulations (exenatide extended-release, dulaglutide, and albiglutide) further improve fasting plasma glucose, which can result in additional A1C lowering. Reductions in body weight and blood pressure appear similar among individual agents, and small increases in heart rate are of unknown clinical relevance. Gastrointestinal adverse events abate over time with continued treatment and are less frequent with longer-acting GLP-1RAs. Hypoglycemia incidence is low but increased when GLP-1RAs are used with insulin secretagogues or insulin. GLP-1RAs target multiple pathophysiologic mechanisms in patients with T2D and improve glycemic control, although there are some differences within this drug class that may be relevant in clinical practice. Therefore, selection of the most appropriate treatment for individual patients is important.
Triplitt C
，Solis-Herrera C
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