Spotlight on statins in diabetes
Recent studies looked at how statins negatively affect glycemic control but improve cardiovascular mortality, as well as the reasons patients with diabetes don't receive prescriptions for statins despite recommendations.
Several recent studies looked at the effects and use of statins in patients with diabetes.
Statins' negative impact on glycemic control was analyzed in a systematic review published by the European Journal of Pharmacology on March 24. It included 67 randomized controlled trials reporting the effects of statin therapy on HbA1c levels and/or homeostatic model insulin resistance (HOMA-IR), including more than 25,000 patients with and without diabetes. In patients with altered glycemic control, statins increased both HbA1c levels and HOMA-IR index (mean differences vs. placebo, 0.21% [95% CI, 0.16% to 0.25%] and 0.31 [95% CI, 0.24 to 0.38], respectively). The finding was also true among those with normal glycemic status, with mean differences of 1.33% (95% CI, 1.31% to 1.35%) and 0.49 (95% CI, 0.41 to 0.58) versus placebo groups, respectively. The study did not find any difference in effect with dose or type of statin, contrary to the authors' hypothesis. Limitations include that more than a third of the included studies did not show significant differences between statins and placebos on the studied outcomes, so the findings were largely driven by a single trial (the JUPITER study). The authors concluded that statins slightly but significantly affect these measures of diabetes and called for future research to study the risk of diabetes with statins “but also the potential compensatory effect on improving cardiovascular risk to better judge the full pharmacologic effects of statins.”
The effect of statins on cardiovascular mortality in patients with type 2 diabetes was the focus of a retrospective study from Taiwan, published by the European Journal of Clinical Pharmacology on April 3. The study cohort included patients age 40 years and older in 2008 to 2020. A total of 422,380 patients taking statins were matched to 427,407 nonusers. Using an inverse probability of treatment-weighted model, researchers found a significant decrease in cardiovascular mortality with statins (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.39 to 0.42). Compared with no statin, pitavastatin was associated with the greatest reduction in cardiovascular mortality, followed by pravastatin, simvastatin, rosuvastatin, atorvastatin, fluvastatin, and lovastatin. The results found the greatest reduction with a statin dose of 0.86 defined daily dose, indicating that higher doses are not always associated with lower risk of cardiovascular mortality, the study authors said. “In fact, the relationship between daily intensity of statin use and cardiovascular mortality exhibits a U-shaped dose–response relationship. This U-shaped pharmacotherapeutic effect is an important consideration when determining the optimal daily dose of statin,” they wrote. The study had a number of limitations, including potential for unmeasured confounding and uncertain generalizability to other populations.
Finally, the reasons why patients with diabetes don't take statins were explored in a study published by the Journal of the American Heart Association on March 28. The analysis used Northern California electronic health record data on 33,461 patients with diabetes and no atherosclerotic cardiovascular disease (mean age, 59 years; 49% women; 36% White patients, 24% Asian patients, and 15% Hispanic patients). Almost half (47%) had no prescriptions for a statin and no mention in their records of a statin allergy. The researchers applied a deep learning natural language processing approach to these 15,576 patients' unstructured electronic health record data, finding that 12,873 (83%) had no mention of a statin in their notes. Among the remaining 2,703 patients, the deep learning algorithm found that statin hesitancy (19%), guideline-discordant practice (19%), and clinical inertia (18%) were the most common causes for nonuse, with statin-associated side effects/contraindications responsible for 12%. Reasons for statin nonuse varied by patient age, race and ethnicity, insurance, and diabetes type. “A deep learning algorithm identified statin nonuse and actionable reasons for statin nonuse in patients with diabetes. Findings may enable targeted interventions to improve guideline-directed statin use and be scaled to other evidence-based therapies,” the study authors concluded.