Predictors of response to glucagon-like peptide-1 receptor agonists: a meta-analysis and systematic review of randomized controlled trials

Sep 22, 2017Acta diabetologica

Factors linked to how people respond to glucagon-like peptide-1 receptor agonist treatments: a combined analysis of clinical trials

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Abstract

A total of 92 trials were identified for assessing the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on HbA1c levels.

In placebo-controlled trials, the mean reduction of HbA1c at 24 weeks with GLP-1 RA was -0.75%.
Shorter-acting GLP-1 RAs may be more effective in patients with lower fasting glucose levels.
Longer-acting GLP-1 RAs could be more effective in patients with higher fasting hyperglycemia.
Obesity and duration of diabetes do not appear to influence the efficacy of GLP-1 RAs.
Liraglutide may be less effective in non-Caucasian and older patients.

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AIMS: The aim of the present meta-analysis is the identification of the characteristics of patients, which predict the efficacy on HbA1c of glucagon-like peptide-1 receptor agonists (GLP-1 RA).

METHODS: A Medline and Embase search for "exenatide" OR "liraglutide" OR "albiglutide" OR "dulaglutide" OR "lixisenatide" was performed, collecting randomized clinical trials (duration > 12 weeks) up to September 2016, comparing GLP-1 RA at the maximal approved dose with placebo or active drugs. Furthermore, unpublished studies were searched in the www.clinicaltrials.gov register. For meta-analyses, the outcome considered were 24- and 52-week HbA1c. Separate analyses were performed, whenever possible, for subgroups of trials based on several inclusion criteria. In addition, meta-regression analyses were performed for comparisons for which 10 or more trails were available.

RESULTS: A total of 92 trials fulfilling the inclusion criteria were identified. In placebo-controlled trials (n = 41), the 24-week mean reduction of HbA1c with GLP-1 RA was - 0.75 [- 0.87; - 0.63]%. Shorter-acting molecules appear to be more effective in patients with lower fasting glucose, whereas longer-acting agents in patients with higher fasting hyperglycaemia. Obesity and duration of diabetes do not seem to moderate the efficacy of GLP-1 RA, whereas in non-Caucasians and older patients liraglutide could be less effective. At 52 weeks, only 9 placebo-controlled trials were available for preventing any reliable analyses.

CONCLUSIONS: Using a variety of approaches (meta-analyses of subgroup of trials, meta-regression, systematic review of subgroup analyses in individual trials, and meta-analyses of subgroups of patients), we identified some putative predictors of efficacy of GLP-1 RA, which deserve further investigation.

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Predictors of response to glucagon-like peptide-1 receptor agonists: a meta-analysis and systematic review of randomized controlled trials

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