Cardiovasc Drugs Ther. 2026 Jun 20. doi: 10.1007/s10557-026-07885-4. Online ahead of print.
ABSTRACT
AIMS: Comprehensive and fine-grained evidence of lipid-lowering drugs in patients with diabetes is lacking. This study aims to compare the efficacy and safety of lipid-modifying agents in this population across agent-, class-, and dose-levels.
METHODS: We systematically searched PubMed, Web of Science, Scopus, the Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov from inception to October, 2025, for randomized controlled trials (RCTs) evaluating lipid-modifying therapies in patients with diabetes. A frequentist network meta-analysis was performed across multiple levels. Primary outcomes included major adverse cardiovascular events (MACE), stroke, myocardial infarction (MI), revascularization, cardiovascular death, and all-cause death. Secondary outcomes were lipid profile parameters. Safety outcomes were also assessed.
RESULTS: Eighteen RCTs involving 14 lipid-modifying agents and 89,717 participants were included. Statins, ezetimibe, PCSK9i and bempedoic acid each reduced the risk of MACE, with distinct agent-specific profiles across cardiovascular and lipid endpoints. Atorvastatin is associated with a strong reduction in multiple cardiovascular outcomes. Reduction in revascularization risk was specifically observed with atorvastatin at both moderate and high dose, while pravastatin was associated with a great reduction in stroke risk. Ezetimibe and evolocumab, with comparable efficacy, were associated with reductions in MI risk. PCSK9i significantly improved TC and LDL-C, while exerting mild effects on TG and HDL-C. Pemafibrate showed a pronounced benefit of TG-lowering efficacy. The renal safety of fibrates and bempedoic acid, and glycometabolism safety of EPA-DHA warrants monitoring.
CONCLUSION: Lipid-modifying therapies were associated with beneficial and specific cardiovascular and lipid effects in diabetes. The results provide more granular and tailored lipid management strategies.
TRIAL REGISTRATION: PROSPERO CRD420251163974.
PMID:42321442 | DOI:10.1007/s10557-026-07885-4