Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review

ABSTRACT

Over the last decade, the discovery of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) has increased the treatment options for patients with type 2 diabetes mellitus (T2DM). GLP-1 RAs mimic the effects of native GLP-1, which increases insulin secretion, inhibits glucagon secretion, increases satiety and slows gastric emptying. This review evaluates the phase III trials for all approved GLP-1 RAs and reports that all GLP-1 RAs decrease HbA1c, fasting plasma glucose, and lead to a reduction in body weight in the majority of trials. The most common adverse events are nausea and other gastrointestinal discomfort, while hypoglycaemia is rarely reported when GLP-1 RAs not are combined with sulfonylurea or insulin. Treatment options in the near future will include co-formulations of basal insulin and a GLP-1 RA.

KEYWORDS:

• GLP-1 receptor agonist
• type 2 diabetes mellitus
• exenatide
• liraglutide
• lixisenatide
• albiglutide
• dulaglutide

Financial & competing interests disclosure

CS Frandsen has received an unrestricted research grant from Novo Nordisk A/S. S Madsbad has served as a consultant or advisor to: Novartis Pharmaceuticals, Novo Nordisk, Merck, Sharp and Dome, Pfizer A/S, Abbott Laboratories, Sanofi Aventis, Astra Zenenca, Johnson & Johnson, Roche, Mankind, BMS, Antarcia, Boehringer Ingelheim, Eli Lilly, Amgen. S Madsbad has received fees for speaking from Novo Nordisk, Merck, Sharp and Dome, Astra Zeneca, Johnson & Johnson, Abbott Laboratories, Pfizer A/S, Roche, Schering-Plough, Sanofi-Aventis, Eli Lilly, Novartis Pharmaceuticals, BMS, Boehringer Ingelheim and Tageta. S Madsbad is a recipient of a research grant from Novo Nordisk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) induce a decrease in HbA1c and fasting plasma glucose among patients with type 2 diabetes mellitus (T2DM).

• GLP-1 RA treatment is accompanied by a reduction in body weight in most patients.

• GLP-1 RAs are subcutaneously administered twice daily, once daily or once weekly.

• The most common adverse events are nausea, diarrhea and gastrointestinal discomfort. Severe hypoglycemia is rarely reported.

• Head-to-head trials report that liraglutide shows the most consistent superiority in HbA1c lowering, although dulaglutide is noninferior to liraglutide in both efficacy and safety.

• Co-formulations of basal insulin and a GLP-1 RA show promising results in glycemic control and will be available for the treatment of T2DM in the foreseeable future.