Review of head‐to‐head comparisons of glucagon‐like peptide‐1 receptor agonists

Oct 30, 2015Diabetes, obesity & metabolism

Direct comparisons of drugs that activate the glucagon-like peptide-1 receptor

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Abstract

Six glucagon-like peptide-1 receptor agonists () are approved for treating type 2 diabetes.

All approved GLP-1RAs were associated with notable reductions in glycated haemoglobin (HbA1c) levels.
Liraglutide resulted in greater HbA1c reductions compared to exenatide formulations and albiglutide.
No significant difference in HbA1c reductions was observed between liraglutide and dulaglutide.
Short-acting GLP-1RAs had greater effects on postprandial glucose levels by delaying gastric emptying.
Longer-acting GLP-1RAs reduced plasma glucose levels consistently over a 24-hour period.
Gastrointestinal disorders, especially nausea and vomiting, were the most frequent adverse events reported.

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Currently, six glucagon-like peptide-1 receptor agonists () are approved for treating type 2 diabetes. These fall into two classes based on their receptor activation: short-acting exenatide twice daily and lixisenatide once daily; and longer-acting liraglutide once daily, exenatide once weekly, albiglutide once weekly and dulaglutide once weekly. The phase III trial of a seventh GLP-1RA, taspoglutide once weekly, was stopped because of unacceptable adverse events (AEs). Nine phase III head-to-head trials and one large phase II study have compared the efficacy and safety of these seven GLP-1RAs. All trials were associated with notable reductions in glycated haemoglobin (HbA1c) levels, although liraglutide led to greater decreases than exenatide formulations and albiglutide, and HbA1c reductions did not differ between liraglutide and dulaglutide. As the short-acting GLP-1RAs delay gastric emptying, they have greater effects on postprandial glucose levels than the longer-acting agents, whereas the longer-acting compounds reduced plasma glucose throughout the 24-h period studied. Liraglutide was associated with weight reductions similar to those with exenatide twice daily but greater than those with exenatide once weekly, albiglutide and dulaglutide. The most frequently observed AEs with GLP-1RAs were gastrointestinal disorders, particularly nausea, vomiting and diarrhoea. Nauseaoccurred less frequently, however, with exenatide once weekly and albiglutide than exenatide twice daily and liraglutide. Both exenatide formulations and albiglutide may be associated with higher incidences of injection-site reactions than liraglutide and dulaglutide. GLP-1RA use in clinical practice should be customized for individual patients, based on clinical profile and patient preference. Ongoing assessments of novel GLP-1RAs and delivery methods may further expand future treatment options.

Key numbers

0.3 to 1.9%

Reduction in HbA1c

HbA1c reductions observed in head-to-head trials.

−2.9 kg

Weight Reduction

Mean weight difference in trials involving .

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Review of head‐to‐head comparisons of glucagon‐like peptide‐1 receptor agonists

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