GLP-1 Agonist Fails to Improve Coronary Flow Reserve in New Study

Short-term use of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide failed to have any significant effect on coronary or peripheral microvascular function in patients with type 2 diabetes (T2DM), according to the results of a small study published recently in Cardiovascular Diabetology.

According to study authors, Rebekka Faber, of Bispebjerg University Hospital, Denmark, and colleagues, other studies have shown that GLP-1 receptor agonists may have some beneficial effects on the cardiovascular system. Therefore, in this study, they explored whether or not short-term GLP-1 receptor agonist treatment had any effect on coronary microcirculation as measured by coronary flow reserve (CFR).

“We did find a trend towards an increase in CFR in the liraglutide treatment allocation alone, although this increase was modest and only of borderline significance,” the researchers wrote. “It is possible that a short-term treatment study is inadequate to induce the structural changes needed for an improvement in the coronary microcirculation.”

The randomized, cross-over study included 24 patients with no history of coronary artery disease, of whom 20 completed the study. Patients were assigned to treatment with liraglutide 1.2 mg once daily or no treatment for 10 weeks after a 2-week wash out period. Echocardiography was used to evaluate the effect of liraglutide on coronary microcirculation.

A small increase in CFR occurred in patients treated with liraglutide (change 0.18; 95% CI, -0.01-0.36); however, there was no significant difference compared with patients who received no treatment (change 0.16; 95% CI, -0.08-0.40).  The researchers noted that they cannot rule out that newly approved 1.8-mg or 3-mg doses of liraglutide “could have improved the effect of liraglutide on CFR further.”

As expected, treatment with liraglutide did significantly reduce HbA1c (P=.01), systolic blood pressure (P=.01), and weight (P=.03) compared with no treatment.

“Despite a significant weight-loss, reduction in HbA1c and systolic blood pressure, we found only a small and nonsignificant improvement in CFR after 10 weeks treatment with liraglutide,” the researchers wrote. “In our short-term treatment study, we therefore conclude that the GLP-1 analogue liraglutide does not have any significant effect on coronary microcirculation in patients with type 2 diabetes.”

References:

Faber R, Zander M, Pena A, Michelsen MM, et al. Effect of the glucagon-like peptide-1 analogue liraglutide on coronary microvascular function in patients with type 2 diabetes–a randomized, single-blinded, cross-over pilot study. Cardiovascul Diabetol. 2015;14:41.