ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacoepidemiology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1554631
Systemic evaluation of inclisiran on risk of new-onset diabetes and hyperglycemia compared to evolocumab and atorvastatin
Provisionally accepted
- 1Fujian Provincial Hospital, Fuzhou, China
- 2Fujian Medical University, Fuzhou, Fujian Province, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Inclisiran is a siRNA-based cholesterol-lowering drug with GalNAc, used for hypercholesterolemia or dyslipidemia. It reduces LDL-C by 50%, with a convenient dosing schedule and fewer adverse events. Unlike statins, inclisiran has not been associated with an increased risk of muscle or liver adverse events in clinical studies. This favorable safety profile makes inclisiran a valuable alternative for patients' intolerant of statins due to muscle or hepatic side effects. However, its impact on glycemic control and diabetes risk is unclear and under-studied.Methods and results: FAERS study analyzed hyperglycemia and diabetes risks for inclisiran, atorvastatin, and evolocumab. Data from 2021-2024 was assessed for MedDRA terms, and SAS 9.4 with ROR and BCPNN was used for analysis. Systematic review and meta-analysis were conducted using PubMed, Embase, and specific search terms. Two researchers extracted data independently, and study quality was assessed with Cochrane and Newcastle-Ottawa Scales. RevMan5.4 and Stata 18.0 were used for analyses. Ethical approval was waived due to public, anonymous data. From 2015 Q1 to 2024 Q1, 12,821,285 adverse events were reported in FEARS, with 3,375 inclisiran, 126,620 evolocumab, and 42,228 atorvastatin cases. Atorvastatin had a higher ROR for type 2 diabetes (195.03) than inclisiran (0.95) and evolocumab, but not statistically significant. Glucose intolerance and blood glucose issues showed weak signals for inclisiran and atorvastatin. A literature search yielded 16 relevant articles, including 6 cohort studies and 10 RCTs, totaling 297,863 patients. Incidence of new-onset diabetes was higher with atorvastatin than inclisiran, placebo, and evolocumab. SUCRA rankings were atorvastatin > inclisiran > placebo > evolocumab for new diabetes incidence.The FAERS study and meta-analysis indicate inclisiran may carry a lower risk of new-onset diabetes compared to atorvastatin, warranting further investigation into inclisiran's impact on glycemic control.
Keywords: Inclisiran, evolocumab, atorvastatin, Hyperglycemia, new-osnet diabetes
Received: 20 Jan 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Fei, Huan, Yuanchun, Lingbin and Sunhui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chen Sunhui, Fujian Provincial Hospital, Fuzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.