Liraglutide Interferes With Beta-Blockade for Variceal Bleeding Prevention

By Will Boggs MD

May 28, 2020

NEW YORK (Reuters Health) - The glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide interferes with the use of beta-blockers for the prevention of bleeding from esophageal varices, according to a case series from Italy.

"It is known that GLP-1 can acutely increase heart rate, although not in a significant way, unless patients suffer from, e.g., heart insufficiency," Dr. Ranka Vukotic of the University of Bologna told Reuters Health by email. "There are no data on the concomitant use of beta-blockers and GLP-1 receptor agonists in diabetic patients with advanced cirrhosis."

Dr. Vukotic and colleagues evaluated 18 consecutive patients with cirrhosis who were receiving propranolol, a noncardioselective beta-blocker, to prevent variceal bleeding while also receiving liraglutide for uncontrolled type 2 diabetes.

All patients had achieved a target heart rate (median, 62 beats/minute) before starting liraglutide treatment. After three months of combined treatment, however, the median heart rate increased to 88 beats/minute and remained relatively stable despite increases in the propranolol dose.

During the study, the authors switched four patients to a different noncardioselective beta-blocker, but this did not result in achievement of the target heart rate.

During follow-up, 15 patients had elective variceal endoscopic band ligation because their heart rates remained out of the optimal range despite the uptitration of the beta-blocker, the authors report in Annals of Internal Medicine.

One patient had acute variceal bleeding, and two had to be hospitalized, one with paroxysmal supraventricular tachycardia and one with persistent atrial fibrillation.

Given that both GLP-1 receptors and beta-adrenergic receptors are co-expressed in the atria and that both types of receptors are G(s)-coupled, the authors speculate that the alpha subunit of the intracellular signaling protein G(s) decreases when propranolol inhibits beta-adrenergic receptors and increases when liraglutide stimulates receptors for GLP-1 and that this interaction accounts for the effects they report.

"Despite not achieving an optimal beta-blockade, we did not observe an increased rate of variceal bleeding in our patients," Dr. Vukotic said. "However, most of them were in both pharmacological and endoscopic prophylaxis, which can be considered a common strategy in this setting."

"Our data are not sufficient to set indications but, as in other contexts where the pharmacological prophylaxis is not optimal, the endoscopic prophylaxis seems to be able to protect from bleeding risk," she said. "What could be interesting is to explore whether other beta-blockers, cardioselective or noncardioselective, might provide different results from those shown with propranolol."

Dr. Thomas Nystroem of Karolinska Institutet, in Stockholm, who recently reported persistent increases in diurnal heart rate in patients treated with liraglutide, told Reuters Health by email, "It is well known that GLP-1RA increases heart rate, but how is not yet solved."

"One should be aware of these findings when treating patients with cirrhosis and type 2 diabetes with GLP-1RA (may be a class effect)," said Dr. Nystroem, who was not involved in the new research. "This is a case report, with a small number of patients, and therefore may not be translated in a broader context."

SOURCE: Annals of Internal Medicine, May 26, 2020.