Investigational glucagon-like peptide-1 agonists for the treatment of obesity

Aug 27, 2016Expert opinion on investigational drugs

New drugs that mimic a natural hormone to help treat obesity

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Abstract

GLP-1 receptor agonists (GLP-1RAs) have been approved for the treatment of type 2 diabetes mellitus (T2DM) and may also be effective for obesity management.

GLP-1RAs are associated with weight reduction in addition to their primary use for T2DM.
Liraglutide is specifically approved for obesity treatment, with other GLP-1RAs also being considered for this indication.
Serious adverse effects are not commonly reported, though potential risks such as pancreatitis and tumors remain uncertain.
Gastrointestinal side effects, notably nausea, are frequent and may limit patient tolerability.
Cardiovascular studies indicate that GLP-1RAs could have beneficial effects in both T2DM and obesity treatment.
New GLP-1RAs with less frequent dosing and potentially lower nausea rates may improve patient adherence.

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INTRODUCTION: Obesity is a worldwide problem predisposing to type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease, cancer and other comorbidities. Lifestyle modification is the first line intervention but adjunctive pharmacotherapy is often required. The GLP-1 receptor agonists (GLP-1RAs) were developed primarily for T2DM and they also reduce body weight. Liraglutide was approved for the treatment of obesity and other GLP-1RAs are likely to be suitable for this indication.

AREAS COVERED: This review describes the GLP-1RAs that have been approved for the treatment of T2DM as potential candidates for the treatment of obesity and the new agents currently under development which may have advantages in patient adherence.

EXPERT OPINION: The GLP-1RAs offer a welcome addition to obesity pharmacotherapy. They appear to be free of serious adverse effects although uncertainty remains about possible risks of pancreatitis and neoplasms. However, they have frequent gastrointestinal side effects, particularly nausea, which limits their tolerability. Cardiovascular outcome studies in T2DM support their use and this is likely to increase in both T2DM and obesity. Other GLP-1RAs which can be given by subcutaneous injection once weekly or less frequently or by oral administration would have advantages especially if nausea is less frequent than with liraglutide.

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Investigational glucagon-like peptide-1 agonists for the treatment of obesity

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