Drug targets for lipid modification and risk of type 2 diabetes: a cis-Mendelian randomization study
Authors' conclusion
This study provides genetic evidence for variation in diabetes-related side-effects of different lipid-modifying drugs, with potential relevance for future clinical trials and individual treatment decisions.
Study context
- Population
- Individual-level data from UK Biobank and Lifelines plus publicly available genome-wide association data; loci ACLY, ANGPTL3, ANGPTL4, APOB, APOC3, CETP, HMGCR, LDLR, LIPG, LPA, MTTP, NPC1L1, PCSK9
- Comparison
- Genetic proxies of lipid-modifying drug targets and risk of T2D, with coronary artery disease (CAD) as contrast outcome
- Outcome
- Prevalent and incident T2D, with CAD as a contrast outcome
Methodological detailscis-genetic instruments weighted for LDL-C, HDL-C, TG and apolipoproteins, UK Biobank, Lifelines and public GWAS data
- Cis-genetic instruments weighted for LDL-C, HDL-C, TG and apolipoproteins
- UK Biobank, Lifelines and public GWAS data
Main finding
As reported in the abstract
T2D and CAD risk by drug target
- HMGCR: predicted to reduce CAD risk and increase T2D risk
- APOC3, LDLR, LPA, MTTP, NPC1L1, PCSK9: predicted to reduce CAD risk without change in T2D risk
- ANGPTL4, CETP: predicted to reduce risk of both CAD and T2D
- ACLY, ANGPTL3, APOB, LIPG: evidence for neither CAD nor T2D
Original publication
Drug targets for lipid modification and risk of type 2 diabetes: a cis-Mendelian randomization study. Cardiovasc Diabetol. Published 14 May 2026. doi:10.
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