NATURE REVIEWS | ENDOCRINOLOGY VOLUME 8 | APRIL 2012

Nature Reviews Endocrinology 8, 196 (2012); published online 31 January 2012; doi:10.1038/nrendo.2012.13

RESEARCH HIGHLIGHTS

Treatment with agonists of the glucagon-like peptide 1 receptor (GLP-1R) induces weight loss in patients with overweight or obesity irrespective of the presence of type 2 diabetes mellitus, report Danish researchers.

Over the past decade, GLP-1—a gut hormone secreted after nutrient ingestion—has emerged not only as an essential regulator of blood glucose levels (through its effect on glucose-stimulated insulin secretion and inhibition of glucagon release) but also as a therapeutic target for the treatment of type 2 diabetes mellitus. The GLP-1R agonists exenatide and liraglutide—which, unlike GLP-1, are not rapidly degraded by dipeptidyl peptidase 4—are known to produce modest but significant

PHARMACOTHERAPY

GLP-1R agonists—the new weapon against obesity?and sustained weight loss in patients with diabetes mellitus.

Using a systematic review and meta-analysis approach, Vilsbøll et al. aimed to determine the risks and benefits of GLP-1R agonists as a means of inducing weight loss versus placebo, no intervention or other antidiabetic interventions in patients with a BMI ≥25 kg/m2 with or without diabetes mellitus. Secondary study end points included the effects of GLP-1R agonists on blood pressure, cholesterol levels, alanine aminotransferase and alkaline phosphatase activity, and the incidence of adverse events.

A total of 25 randomized controlled trials, the results of which were published between January 2004 and May 2011, matched the inclusion criteria. The

investigators of three trials enrolled exclusively patients without diabetes mellitus. Study participants received exenatide twice daily or once weekly in 13 and four trials, respectively, and liraglutide in eight trials, over a period of ≥20 weeks.

A random-effects meta-analysis, which included 3,395 individuals randomly allocated to receive GLP-1R agonists and 3,016 controls from 21 trials, showed that treatment with GLP-1R agonists led to greater weight loss in the GLP-1R group than in control groups (–2.9 kg, 95% CI –3.6 to –2.2 kg) and reduced blood pressure and cholesterol levels. Higher GLP-1R agonist doses produced the greatest effects on body weight; however, these doses also increased the frequency of adverse events, such as hypoglycemia and gastrointestinal adverse events. Weight loss was observed in patients with and without diabetes mellitus; those without this disorder achieved greater reductions in body weight than those with the disease.

Despite these promising results, whether GLP-1R agonists can be broadly recommended as weight reduction agents must be clarified further. Of note, body weight was a secondary, not primary, end point in most trials analyzed by Vilsbøll and colleagues. Overall, the safety of GLP-1R agonists remains a concern.

Linda Koch

Original article Vilsbøll, T. et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 344, d7771 (2012)

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