The following is a summary of “Statins, Type 2 Diabetes, and Body Mass Index: A Univariable and Multivariable Mendelian Randomization Study,” published in the February 2023 issue of Endocrinology & Metabolism by Yang, et al.

For a study, researchers sought to investigate the potential diabetogenic effects of commonly used lipid modifiers such as statins, PCSK9 inhibitors, and ezetimibe, and the role of body mass index (BMI) in mediating these effects. 

They used genetic variants that mimic commonly used lipid modifiers such as statins, PCSK9 inhibitors, and ezetimibe. They then analyzed the associations between these lipid modifiers and type 2 diabetes risk, glycated hemoglobin (HbA1c), fasting insulin, fasting glucose, and BMI using the largest relevant genome-wide association studies (GWAS) available for people of European ancestry and, where possible, for East Asians. To investigate the role of lipid modifiers independent of BMI, they used multivariable Mendelian randomization (MR) analysis.

The results showed that genetically mimicked effects of statins and ezetimibe, but not PCSK9 inhibitors, were associated with a higher risk of type 2 diabetes(odds ratio [OR] 1.74 [95% CI, 1.49 to 2.03]; 1.92 [1.22 to 3.02]; 1.06 [0.87 to 1.29] per SD reduction in low-density lipoprotein (LDL)-cholesterol). Of these lipid modifiers, only genetically mimicked effects of statins were associated with higher BMI, with a difference of 0.33 standard deviation (95% CI, 0.29 to 0.38) per standard deviation reduction in LDL-cholesterol, explaining 54% of the total effect of statins on type 2 diabetes risk.

In conclusion, the study suggested that higher BMI mediates more than half of the diabetogenic effects of statins but not other commonly used lipid modifiers. Further research was needed to understand the drug-specific mechanisms underlying the effects of lipid modifiers on type 2 diabetes.

Reference: academic.oup.com/jcem/article-abstract/108/2/385/6746562?redirectedFrom=fulltext