A case for screening real-world data for collateral drug benefits: Glucagon-like peptide 1 receptor agonists and bile acid diarrhea

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Purpose: Collateral drug benefits are hitherto unknown beneficial effects that might lead to repurposing of already marketed drugs. A randomized controlled trial has found liraglutide to be non-inferior to colesevelam in reducing bile acid diarrhea. We hypothesized that this collateral drug benefit of liraglutide could have been detected using observational data. Methods: We performed a sequence symmetry analysis (SSA). In the SSA, we indexed individuals on the date of the first prescription of GLP1-RA and restricted the analysis to all individuals who had a first prescription of bile acid sequestrants between 365 days prior to until 365 days after the index date. Sequence ratios (SR), that is, the ratio between counts of persons initiating GLP1-RA first versus last, were calculated, and 95% confidence intervals were obtained. We adjusted for prescribing trends using null-effect SR adjustment. Results: We included 158 individuals, with a median age of 58 years. The trend-adjusted SR was 0.96 (95% confidence interval 0.70–1.31). When stratifying on the type of GLP1-RA (liraglutide or semaglutide), we found results compatible with the previous trial (SRliraglutide 0.75, 0.51–1.10 and SRsemagltuide 1.23, 0.80–1.89). Since BAS also can be used as a cholesterol lowering drug, we repeated the main analysis while excluded statin users, resulting in a stronger association (SR 0.56, 0.33–0.96). Conclusion: Using the SSA methodology, we obtained estimates of a collateral drug benefit that were compatible with trial results. These results support the use of epidemiological analyses of observational data as instrument for detecting collateral drug benefits.

TidsskriftPharmacoepidemiology and Drug Safety
Udgave nummer1
StatusUdgivet - jan. 2024

Bibliografisk note

Funding Information:
Martin Torp Rahbek reports no conflicts of interest. Lars Christian Lund reports participation in research projects funded by Menarini Pharmaceuticals and LEO Pharma, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the current work. Jesper Hallas reports participation in post authorization safety studies funded by Novo Nordisk with money paid to his employer and with no personal fees involved.

Publisher Copyright:
© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.


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