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Review
. 2015 Feb;6(1):19-28.
doi: 10.1177/2042018814559725.

GLP-1 receptor agonists: a review of head-to-head clinical studies

Jennifer M Trujillo  1 , Wesley Nuffer  2 , Samuel L Ellis  2
Affiliations
Review

GLP-1 receptor agonists: a review of head-to-head clinical studies

Jennifer M Trujillo et al. Ther Adv Endocrinol Metab. 2015 Feb.

Erratum in

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are attractive options for the treatment of type 2 diabetes (T2D) because they effectively lower A1C and weight while having a low risk of hypoglycemia. The GLP-1 RA class has grown in the last decade with several agents available for use in the US and Europe and several more in development. Since the efficacy and tolerability, dosing frequency, administration requirements, and cost may vary between agents within the class, each agent may offer unique advantages and disadvantages. Through a review of phase III clinical programs for exenatide twice daily, exenatide once weekly, liraglutide, albiglutide, lixisenatide, and dulaglutide, eight head-to-head trials have evaluated the safety and efficacy of GLP-1 RA active comparators. The purpose of this review is to provide an analysis of these trials. The GLP-1 RA head-to-head clinical studies have demonstrated that all GLP-1 RA agents are effective therapeutic options at reducing A1C. However, differences exist in terms of magnitude of effect on A1C and weight as well as frequency and severity of adverse effects.

Keywords: GLP-1 receptor agonist; type 2 diabetes.

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Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Changes in A1C values with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in head-to-head clinical studies. p-values are for statistical superiority unless otherwise noted as noninferiority; *p < 0.0025, †p < 0.0001, ‡p = 0.02, §p = not significant, noninferiority p-value not reported (95% confidence interval 0.033–0.297, meeting predefined noninferiority margin), ¶ noninferiority p-value = 0.846 (not meeting predefined noninferiority margin), **p < 0.001 for both doses of dulaglutide versus exenatide bid, ††p = not significant, noninferiority p-value < 0.0001 (meeting predefined noninferiority margin).
Figure 2.
Figure 2.
Changes in weight with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in head-to-head clinical studies. p-values are for statistical superiority (unless noted for noninferiority); *p = not significant, †p = 0.0005, ‡p-value not reported for weight difference of 1.02 kg (95% confidence interval 0.456–1.581), §p < 0.0001, ¶ p < 0.001 versus dulaglutide 0.75 mg, **p = not significant between dulaglutide 1.5 mg versus exenatide bid, ‡‡p = 0.011.
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