Liraglutide increases insulin sensitivity without causing weight loss: Study
Los Angeles: Research published in 'Diabetes' showed that a glucagon-like peptide-1 receptor (GLP-1R) agonist, a kind of medicine used to treat type 2 diabetes and obesity, can lead to a quick increase in insulin sensitivity.
Insulin sensitivity refers to how sensitive cells are to insulin, a hormone that regulates blood glucose levels. Increased insulin sensitivity indicates that insulin can reduce blood glucose levels more efficiently.
Type 2 diabetes is characterised by decreased insulin sensitivity or insulin resistance. Improved insulin sensitivity can therefore lower the chance of developing Type 2 diabetes or enhance therapy.
GLP-1R agonists are drugs that impact metabolism by increasing insulin secretion and thereby lowering blood sugar levels.
Dipeptidyl peptidase 4 (DPP-4) inhibitors prevent the breakdown of the body's own endogenous GLP-1, as well as other peptide hormones such as glucose-dependent insulinotropic peptide (GIP).
"We know that GLP-1R agonists promote weight loss, but we were surprised to find that the GLP-1R agonist liraglutide also has rapid effects on insulin sensitivity, independent from weight loss," said Mona Mashayekhi, MD, PhD, assistant professor of medicine in the Division of Diabetes, Endocrinology and Metabolism.
"This effect requires activation of the GLP-1 receptor, but increasing the body's own endogenous GLP-1 through the use of the DPP4 inhibitor sitagliptin does not achieve similar effects."
"Our research suggests that liraglutide, and presumably other GLP-1R agonists, are having important metabolic effects in a way that's different from increasing endogenous GLP-1 levels, even though they're using the same receptor. Future research will focus on potential mechanisms of how GLP-1R agonists are improving insulin sensitivity independent of weight loss."
Eighty-eight individuals with obesity and pre-diabetes were randomized for 14 weeks to receive the GLP-1R agonist liraglutide, the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin, or weight loss without drug using a low-calorie diet.
To further investigate the GLP-1R-dependent effects of the treatments, the GLP-1R antagonist exendin and a placebo were given in a two-by-two crossover study during mixed meal tests. Crossover studies allow the response of a subject to treatment A to be compared with the same subject's response to treatment B.
Liraglutide was shown to rapidly improve insulin sensitivity as well as decrease blood glucose within two weeks of beginning treatment and before any weight loss.
"GLP-1R agonists are an exciting class of medications, given their strong glucose-lowering effects combined with tremendous weight-loss benefits, and they have transformed how we manage diabetes and obesity in the clinic," Mashayekhi said.
"Since the number of medications in this class is rapidly expanding, a deeper understanding of the mechanisms of benefit is crucial so we can design the right drugs for the desired effects in the right patients."
