Adding prandial GLP-1 receptor agonists to basal insulin: a promising option for type 2 diabetes therapy

Abstract

Background: Diabetes mellitus is a serious and increasingly prevalent condition in Canada and around the world. Treatment strategies have become increasingly complex, with a widening array of pharmacological agents available for glycemic management in type 2 diabetes mellitus (T2DM). New therapies that act in concert with available basal insulins may represent alternatives to basal insulin intensification with prandial or pre-mixed insulin. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently shown promise as useful additions to basal insulin, with significant reductions in glycated hemoglobin and potentially beneficial effects on body weight. This review will focus on pivotal clinical trials to assess the potential benefits of adding prandial GLP-1 RAs to basal insulin in patients with T2DM.

Methods: Clinical studies combining prandial GLP-1 RAs and basal insulin (published between 2011 and July 2017) were identified and reviewed in PubMed, the Cochrane Central Register of Clinical Trials (Issue 6, June 2017), and clinicaltrials.gov.

Results: Most of the studies presented in this review show that the addition of a prandial GLP-1 RA to basal insulin results in equal or slightly superior efficacy compared to the addition of prandial insulin, together with weight loss and less hypoglycemia.

Conclusions: The results of the studies suggest that a prandial GLP-1 RA as an add-on to basal insulin may be a safe and effective treatment intensification option (vs basal-plus or basal-bolus insulin).

Keywords:

• Diabetes guidelines
• insulin
• prandial glucagon-like peptide-1 receptor agonists
• type 2 diabetes mellitus

Transparency

Declaration of funding

This review was funded by Sanofi Canada.

Declaration of financial/other relationships

R.M.G.: Research support from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Medtronic, Merck, Novartis, Novo Nordisk, Roche, Sanofi, and Takeda; served on advisory panels for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Novo Nordisk, Roche, Sanofi, and Takeda; speaker bureaus for Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novo Nordisk, Sanofi, and Servier; consultant for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Janssen, Novo Nordisk, and Takeda. L.B.: Consultant and/or speaker bureau for Abbott, AstraZeneca, Bayer, BD, Boehringer Ingelheim, Eli Lilly, Janssen, LifeScan, Merck, MontMed, Novo Nordisk, and Sanofi. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work and have declared unrestricted grants from AstraZeneca A/S for research purposes, and have served as a consultant to all the manufacturers of GLP-1 RAs on the market.

Acknowledgments

Research and editorial assistance in developing this manuscript were provided by Dr Sonja Basta (Freelance Medical Writer, Kingston, Ontario) and Wendy Marston (Freelance Medical Writer, Montreal, Quebec). They acknowledge the unrestricted support of Sanofi Canada for making this assistance possible.