This Mendelian randomization (MR) study investigated whether three classes of cholesterol-lowering drugs—HMGCR inhibitors (eg, statins), PCSK9 inhibitors, and NPC1L1 inhibitors—causally affect the risk of diabetic microvascular complications. Using genetic data from genome-wide association studies, researchers examined the relationship between these drug targets and key complications including diabetic nephropathy, retinopathy, and neuropathy. Genetic proxies for drug exposure were analyzed for their impact on LDL-C levels and downstream microvascular disease in patients with diabetes, with coronary artery disease used as a positive control.

Results revealed that HMGCR inhibition was strongly associated with increased risks of diabetic nephropathy, retinopathy, and neuropathy. Similarly, PCSK9 inhibition was linked to elevated risks of nephropathy and neuropathy. In contrast, inhibition of NPC1L1 appeared protective against diabetic retinopathy. These findings suggest that while certain cholesterol-lowering therapies may increase microvascular risk in diabetes, NPC1L1 inhibitors could hold potential for targeted protection—highlighting the need for personalized lipid management in diabetic populations.

Reference: Yang B, Yao B, Zou Q, Li S, Yang S, Yang M. Causal Association Between Cholesterol-Lowering Drugs and Diabetic Microvascular Complications: A Drug-Target Mendelian Randomization Study. J Diabetes Res. 2025;2025:3661739. doi: 10.1155/jdr/3661739.