Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Lipid-Lowering Therapies & Risk of Diabetes

In a systematic review and meta-analysis of 33 randomized controlled trials (RCTs), no independent association between reduction in low-density lipoprotein cholesterol (LDL-C) and incident diabetes mellitus (DM) was found among intensive lipid-lowering therapies. The RCTs included 21 of statins, 12 of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and 0 of ezetimibe. A total of 163,688 patients without diabetes were randomly assigned to more intensive (n=83,13) or less intensive (n=80,565) lipid-lowering therapies. Researchers found:

  • No significant association was observed between reduction in LDL-C and incident DM for more intensive lipid-lowering therapy, or for statins or PCSK9 inhibitors.
  • More intensive lipid-lowering therapy was associated with a higher risk of incident DM vs less intensive therapy.
  • PCSK9 inhibitors had no association with risk of incident DM.


Khan SU, Rahman H, Okunrintemi V, et al. Association of lowering low-density lipoprotein cholesterol with contemporary lipid-lowering therapies and risk of diabetes mellitus: A systematic review and meta-analysis. [Published online ahead of print March 22, 2019]. J Am Heart Assoc. doi:10.1161/JAHA.118.011581.


Many patients refuse to take statin medications because of fear of side effects including the risk of developing diabetes mellitus (DM). This meta-analysis of 33 trials showed no significant association with a 1 mmol/L (about 38 mg/dL) reduction in LDL and incident DM. Use of high intensity statins compared to less intense treatment, however, showed a 7% relative risk and 0.3% absolute risk of incident DM. There was no association between use of PSCK9 inhibitors and DM suggesting that incident DM is a statin risk and not a risk associated with LDL reduction. Previous studies have suggested that the development of DM while on statin therapy occurs in individuals that already have insulin resistance and that the development of DM does not modify the ASCVD risk reduction achieved by statin therapy. —Matthew Sorrentino, MD