Participants in a randomized controlled trial who took liraglutide were more likely to develop gallbladder stones and other complications of the gallbladder and biliary tract vs. those who took placebo, according to findings published in Diabetes Care.
Michael A. Nauck, MD, head of clinical research of the Diabetes-Center Bochum-Hattingen at St. Josef-Hospital of Ruhr-University Bochum in Bochum, Germany, and colleagues performed a secondary analysis of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial. The trial had a randomized controlled design and examined the differences in instances of cardiovascular death, myocardial infarction and stroke among adults with type 2 diabetes across 3.8 years of median follow-up time. Participants were assigned to a regimen of 1.8 mg per day of liraglutide (Victoza, Novo Nordisk) or placebo.
In Nauck and colleagues’ analysis, they collected data from the primary results on reported instances of uncomplicated gallbladder stones, complicated gallbladder stones, cholecystitis and biliary obstruction, which were all together defined as “gallbladder or biliary tract-related events.” Such events occurred for 141 of the participants who took liraglutide (mean age, 65.4 years; 39% women) and for 88 of the participants who took placebo (mean age, 65 years; 39.8% women).
Specifically, 16 participants in the liraglutide group and five in the placebo group had uncomplicated gallbladder stones; 52 participants taking liraglutide and 40 taking placebo had complicated gallbladder stones; and 51 participants taking liraglutide had cholecystitis vs. 33 of those in the placebo group. A biliary obstruction occurred for 25 participants in the liraglutide group and 16 participants in the placebo group.
Participants in a randomized controlled trial who took liraglutide were more likely to develop gallbladder stones and other complications of the gallbladder and biliary tract vs. those who took placebo.
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The researchers noted that it was 1.6 times more likely that a participant taking liraglutide would experience a gallbladder or biliary tract event compared with those taking placebo (HR = 1.6; 95% CI, 1.23-2.09).
Cholecystectomy rates were similar between groups, 57% of participants in the liraglutide and 59% in the placebo group 59%. Those taking liraglutide were 1.56 times more likely to have a cholecystectomy than those in the placebo group (HR = 1.56; 95% CI, 1.1-2.2).
Participants taking liraglutide who experienced a complication of the gallbladder or biliary tract lost an average of 5.3 kg during the trial compared with an average of 3 kg in those who did not have a complication and took the medication. Participants in the placebo group who had a complication lost an average of 3.3 kg vs. an average loss of 0.6 kg among placebo group members who did not experience a complication. Ultimately, the researchers found that complications were 4% more likely for every 1 kg reduction in weight.
“Overall, the mechanism for the increased occurrence of gallbladder stones with liraglutide remains unclear, but it may involve altered bile acid production and secretion, decreased gallbladder emptying, weight loss or a combination of all of these,” the researchers wrote. “A further, recently proposed explanation for the gallbladder events observed in GLP-1 [receptor agonist] clinical trials is GLP-1 [receptor agonist]-induced prolongation of gallbladder refilling.” – by Phil Neuffer
Disclosures: Nauck reports he has served on the advisory boards for AstraZeneca, Berlin-Chemie, Eli Lilly, Fractyl, Hanmi, Intarcia Therapeutics/Servier, Merck Sharp & Dohme and Novo Nordisk; received lecture fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Eli Lilly, Medscape, Merck Sharp & Dohme and Novo Nordisk; received travel support from Berlin-Chemie, Eli Lilly, Intarcia Therapeutics/Servier, Merck Sharp & Dohme and Novo Nordisk; and received grant support from AstraZeneca, Eli Lilly, GlaxoSmithKline, Intarcia Therapeutics/Servier, Merck Sharp & Dohme, Novartis and Novo Nordisk. Please see the study for all other authors’ relevant financial disclosures.