Based on the findings, "physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 RAs for treatment in clinical practice," researchers write in JAMA Internal Medicine.
The analysis, by Dr. Huabing Zhang and colleagues from the Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing, included 76 randomized clinical trials that compared use of GLP-1 RAs with placebo or with non-GLP-1 RAs in adults. Together, the trials had more than 103,000 participants (mean age, 58 years; 41% women).
Among all trials, use of a GLP-1 RA was associated with a 37% increase in the relative risk of gallbladder or biliary disease (relative risk, 1.37; 95% CI, 1.23 to 1.52). The absolute risk difference was modest, corresponding to 27 more events per 10,000 persons per year.
Treatment with a GLP-1 RA was associated with significantly increased risks for cholelithiasis (RR, 1.27), cholecystitis (RR, 1.36) and biliary disease (RR, 1.55).
Use of GLP-1 RA was associated with higher risks of gallbladder or biliary diseases at higher doses (RR, 1.56), but not at lower doses (RR, 0.99), and when used for more than 26 weeks (RR, 1.40) but not for shorter durations (RR, 0.79).
GLP-1 RA use for weight loss showed stronger effects on risk of gallbladder or biliary diseases (RR, 2.29) than for type-2 diabetes or other indications (RR, 1.27).
"Gallbladder disease has been reported as an adverse event in the published reports and/or the supplemental materials of most of the randomized clinical trials of GLP-1 RAs; however, to our knowledge, biliary diseases have seldom been reported," the authors point out.
They note that only 20 of the 76 trials included the review clearly reported biliary-related events, "suggesting potential under reporting. Given the findings of this review and analysis, studies of GLP-1 RAs should fully report biliary-related events," Dr. Zhang and colleagues suggest.
The co-authors of an invited commentary note that the analysis had a sufficient sample size to detect modest differences in event rates between groups, and included the newer GLP-1 RAs, such as oral semaglutide.
However, Dr. Shanzay Haider and Dr. Kasia Lipska of Yale School of Medicine, in New Haven, Connecticut, caution, that the trials included were not designed to specifically assess gallbladder or biliary diseases. Instead, these events were captured as part of routine monitoring for adverse events.
They also say it's unclear whether the gallbladder and biliary complications were directly due to the weight loss associated with GLP-1 RA use or with other mechanisms.
The higher-risk signal in GLP-1 RA trials for weight-loss indications may be due to more weight loss achieved in those trials and/or to the higher doses of GLP-1 RAs typically used for weight loss, they point out.
For now, it also remains unclear which patients are at the greatest risk for developing gallbladder and biliary complications from GLP-1 RA drug therapy, Dr. Haider and Dr. Lipska say.
"Clinicians and patients need to consider these findings in the context of an individual's specific situation. Ultimately, the decision to start, continue, or change the dose of a GLP-1 RA should be reached through a collaborative and individualized discussion between a clinician and a patient," they conclude.
The study had no commercial funding and the authors have no relevant disclosures.
SOURCE: https://bit.ly/3LDUPBh and https://bit.ly/3Dx89od JAMA Internal Medicine, online March 28, 2022.
By Reuters Staff
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