Weekly GLP-1 receptor agonists may reduce HbA1c and fasting glucose

1. In this systematic review and meta-analysis, the use of weekly glucagon-like peptide-1 receptor agonists (GLP1-RAs) was associated with a significant reduction in fasting glucose and HbA1c when compared to placebo.

2. Of the weekly GLP1-RAs compared, duraglutide, exenatide and taspoglutide were associated with the greatest decrease in fasting glucose and HbA1c, although high dose taspoglutide (20 mg) was associated with increased risk of nausea compared to other GLP1-RAs.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are a relatively new type of therapy targeting high blood sugar in patients with type 2 diabetes mellitus (T2DM). Development of weekly GLP1-RAs may reduce side effects and increase adherence to these drugs, all of which can be injected. However, while prior research has compared GLP1-RAs to other diabetes treatments, there have been no comparisons of the efficacy or side effects of different weekly GLP1-RAs. This study used a specialized statistical method—a “network meta-analysis”—to combine results from trails of different GLP1-RAs. Four different GLP1-RA drugs—albiglutide, dulaglutide, exenatide, and taspoglutide—were compared to placebo and to each other to determine relative efficacy and side effects. Overall, all drugs reduced short-term and long-term blood sugar compared to placebo. Three drugs—duraglutide, exenatide, and taspoglutide—resulted in the greatest decreases in short-term and long-term blood sugar markers, as well as body weight. No differences were found between drugs in risk of symptomatic low blood sugar. However, taking taspoglutide at a high dose was associated with increased incidence of nausea compared to taking the other drugs. Notably, several of the trials included in this analysis were sponsored by pharmaceutical companies, raising the possibility of publication bias. Nevertheless, in the absence of trials directly comparing these therapies, this study provides the best evidence to date on the comparative effectiveness of several weekly GLP1-RA drugs. These results may guide clinical decision-making, and set an agenda for comparative clinical trials.

Click to read the study published today in the Annals of Internal Medicine

Relevant Reading: Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A review of their efficacy and tolerability

In-Depth [systematic review and network meta-analysis]: This network meta-analysis drew data from 34 randomized controlled trials (21,126 participants) comparing weekly-administered GLP1-RAs to other glucose-lowering drugs or placebo. Use of each drug was associated with significantly decreased HbA1c compared to placebo; mean HbA1c reduction ranged from 1.4% (95%CI 1.6%-1.2%) for dulaglutide 1.5 mg to 0.9% (95%CI 1.2%-0.8%) for taspoglutide 10 mg. In the network meta-analysis, dulaglutide 1.5 mg out-performed all other drugs except for exenatide in terms of HbA1c reduction. All drugs were associated with significant reductions in fasting blood sugar, ranging from decreases of 2.2 mmol/L (95%CI 2.6-1.8mmol/L) for exenatide to 1.5 mmol/L (95%CI 1.9-1.1mmol/L) for albiglutide. In the network meta-analysis, use of exenatide was associated with significantly decreased fasting blood sugar compared to all drugs except high-dose (20 mg) taspoglutide and high-dose (1.5 mg) dulaglutide. All drugs significantly increased risks for nausea compared to placebo, and taspoglutide 20 mg was associated with significantly increased risks of nausea compared to all other drugs.

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