Early use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in Type 2 diabetes

Abstract

Objective:

To evaluate the efficacy and safety of the available glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exenatide and liraglutide (marketed as Byetta and Victoza, respectively) in first- or second-line pharmacotherapy for type 2 diabetes (T2D), described here as ‘early use’.

Research design and methods:

MEDLINE, EMBASE and Google Scholar databases were queried for clinical trial reports using the terms incretin, GLP-1, exenatide and liraglutide. Relevant articles were those that employed these agents in treatment-naïve patients with T2D and in patients who had failed on metformin monotherapy. Additional targeted searches were conducted on diabetes treatment guidelines and on the range of physiological responses to GLP-1 RAs. Most evidence is level I and II.

Results:

Effective therapy for T2D should be implemented early in the course of this progressive disease. The recently revised 2013 Canadian Diabetes Association (CDA) guidelines now identify the GLP-1 RAs among various injected and oral agents recommended for the management of T2D. The rationale for early use of GLP-1 RAs in T2D management is manifold: these agents offer effective management of hyperglycemia in early-stage T2D, minimal risk of hypoglycemia, weight loss, improvement in multiple non-glycemic cardiovascular risk factors, and potential enhancement of patient adherence to antihyperglycemic treatment. Available data from clinical trials support second-line use of GLP-1 RAs among patients who fail on metformin, as well as first-line use of these agents in a subset of T2D patients.

Conclusions:

The ability to achieve glycemic targets using GLP-1 RAs while simultaneously avoiding hypoglycemia and weight gain could provide substantial reassurance to physicians and patients who might otherwise resist the transition to injected therapies. Exenatide and liraglutide represent appropriate second-line choices for pharmacological treatment of T2D, as indicated in the 2013 CDA guidelines.

Keywords::

• Exenatide
• Hypoglycemia
• Liraglutide
• Obesity
• Type 2 diabetes

Transparency

Declaration of funding

The authors gratefully acknowledge Novo Nordisk Canada Inc. for their support of our independent work on this project.

Declaration of financial/other relationships

S.A.R. has received honoraria from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, AstraZeneca and Merck for continuing medical education lectures. J.B. has received honoraria from Novo Nordisk, Eli Lilly, Merck, and Primary Care Network for educational programs as well as grant support from Novo Nordisk and Eli Lilly.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank John Ashkenas PhD and Peter Janiszewski PhD, both of SCRIPT in Toronto, ON, for editorial assistance.

Notes

*Byetta is a registered trade name of Eli Lilly Canada Inc., Toronto, ON, Canada

†Victoza is a registered trade name of Novo Nordisk, Mississauga, ON, Canada