Liraglutide Exerts Weight Loss-Independent, GLP-1R-Dependent Effects

Jan 17, 2024

TUESDAY, Jan. 16, 2024 (HealthDay News) — Use of the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide exerts weight loss-independent, GLP-1R-dependent effects on insulin sensitivity, according to a study published online Oct. 24 in Diabetes.

Mona Mashayekhi, M.D., Ph.D., from Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues examined whether GLP-1R agonists exert weight loss-independent, GLP-1R-dependent effects that differ from those of increasing endogenous GLP-1. Individuals with obesity and prediabetes were randomly allocated to receive 14 weeks of the GLP-1R agonist liraglutide, a hypocaloric diet, or the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin.

The researchers found that weight loss occurred with liraglutide and diet but not sitagliptin. After two weeks, prior to weight loss, liraglutide improved insulin sensitivity measured by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment 2 (HOMA2), and the Matsuda index. Reductions in fasting and postprandial glucose, insulin, C-peptide, and fasting glucagon levels were also seen with liraglutide. In contrast, improvements were seen in insulin sensitivity by HOMA-IR and HOMA2 but not Matsuda index with diet-induced weight loss. However, there was no reduction in glucose levels. Increases in endogenous GLP-1 and gastric inhibitory peptide (GIP) values were seen with sitagliptin with no alteration of insulin sensitivity or fasting glucose, and reductions were seen in postprandial glucose and glucagon. Sitagliptin increased GIP, with no alteration in weight.

“We were surprised to find that the GLP-1R agonist liraglutide also has rapid effects on insulin sensitivity, independent from weight loss,” Mashayekhi said in a statement. “Increasing the body’s own endogenous GLP-1 through the use of the DPP-4 inhibitor sitagliptin does not achieve similar effects.”

Two authors disclosed ties to industry. Novo Nordisk provided liraglutide and matching placebo for the study.

Abstract/Full Text (subscription or payment may be required)