GLP-1 Receptor Agonists for Type 2 Diabetes Mellitus: Recent Developments and Emerging Agents

Abstract

More than 26 million people in the United States have type 2 diabetes mellitus (T2D). Many treatment options exist, but achieving long-term glycemic control in patients with T2D remains challenging. The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offer a treatment option that improves glycemic control and reduces weight, with a low risk of hypoglycemia. They have emerged as attractive options for the treatment of T2D, and significant advances and developments continue to be published regarding these agents. To identify relevant literature on emerging issues related to GLP-1 RAs, a search of the MEDLINE database was performed. Studies published in English evaluating the safety and efficacy of GLP-1 RAs were analyzed. Because of their advantages and unique mechanism of action, GLP-1 RAs are currently being studied in new clinical areas, including in combination with basal insulin, as adjunctive therapy in type 1 diabetes, and for weight loss. In addition, there are several emerging agents in development. Lixisenatide is a once-daily GLP-1 RA that targets postprandial glucose and may be most useful when added to basal insulin as an alternative to rapid-acting insulin. Albiglutide and dulaglutide are once-weekly GLP-1 RAs that may offer more convenient dosing. The most common adverse effects of all GLP-1 RA agents are gastrointestinal (e.g., nausea, diarrhea, and vomiting), but the rates of occurrence vary among agents. Due to the differences in pharmacokinetics, efficacy, rates of adverse effects, and administration requirements within the GLP-1 RA class, each agent should be evaluated independently. The future of GLP-1 RAs offers broader treatment options for T2D as well as potential in other treatment areas.

GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women

“…The GLP-1 RAs potentiate glucose-induced insulin secretion, inhibit glucagon release, delay gastric emptying and reduce appetite, thereby inducing weight loss (9 -12). Thus, GLP-1 RAs are now widely used in the treatment of T2DM (13,14) and their potential in preventing diabetes in prediabetic individuals is being intensively investigated (12,(15)(16)(17). Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recently approved liraglutide 3.0 mg (Saxenda®) as treatment for chronic weight management in obesity (18,19) but the effect of GLP-1 RAs on bone in obese nondiabetic individuals undergoing weight loss is unknown.…”

Effects of Once-Weekly Dulaglutide on Glycemic Control and Renal Function in Patients with Advanced-Stage Diabetic Nephropathy

“…Glucagon-like peptide-1 (GLP-1) receptor agonists are analogs of human GLP-1 that have a high homology to the endogenous human GLP-1 (5). GLP-1 receptor agonists enhance glucose-dependent insulin secretion from the pancreatic beta cell, and suppress inappropriate glucagon secretion leading to decreased blood glucose levels (6).…”

Glucagon receptor antagonist and GIP agonist combination for diet-induced obese mice

“…Notwithstanding encouraging preclinical data (Bagger et al 2011, Trujillo & Nuffer 2014, the progression Values are mean ± s.e.m. for eight mice.…”