Differential effects of prandial and non-prandial GLP-1 receptor agonists in type 2 diabetes therapy

Abstract

In type 2 diabetes mellitus (T2DM), decreased pancreatic beta-cell function and increased insulin resistance contribute to a steady decline in glucose homeostasis. Maintaining levels of glycated hemoglobin ≤7.0% is thought to reduce the microvascular and possibly macrovascular complications that result if T2DM is not properly managed. Recent guidelines have recognized the importance of postprandial glucose (PPG) control in reducing cardiovascular risks, and have recommended a more patient-centered approach. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) mimic the action of the endogenous gastrointestinal hormone GLP-1 to activate the insulin response in pancreatic beta cells in a glucose-dependent manner. Prandial GLP-1 RAs have a short plasma half-life and are particularly effective at targeting PPG elevations, whereas long-acting non-prandial GLP-1 RAs are more effective at reducing fasting plasma glucose. These differences highlight the potential for treatment with these agents to be tailored to the need of individual patients and their glycemic imbalance. All GLP-1 RAs are being evaluated in long-term cardiovascular outcome trials. To date, the only cardiovascular trial that has been completed is the ELIXA trial for lixisenatide, which was found to meet the pre-specified criterion of non-inferiority versus placebo in terms of cardiovascular outcomes.

Keywords:

• Type 2 diabetes
• GLP-1 receptor agonist
• drug safety
• drug efficacy

Declaration of interest

Editorial assistance was provided by J Chebukati, PhD, of MedErgy and by R Gadiot, PhD, of Excerpta Medica, and was funded by Sanofi US, Inc. The author was not compensated and retained full editorial control over the content of this manuscript. The author has received honoraria and/or consultant fees from Amgen, AspireBariatrics, AstraZeneca, Boston Therapeutics, GlaxoSmithKline, Janssen, MSD, NovoNordisk, Sanofi, and Takeda. The author has 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.

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