Time-varying and dose-dependent effect of long-term statin use on risk of type 2 diabetes: a retrospective cohort study

Abstract

Background: We evaluated the effect of statin use on new-onset type 2 diabetes among individuals without atherosclerotic cardiovascular disease (ASCVD) using nationally representative South Korean claims data (2002-2013, N = 1,016,820). Methods: A total of 13,698 patients (statin users 5273, non-statin users 5273) aged 40-74 years, newly diagnosed with dyslipidemia but without any history of diabetes or ASCVD, were selected in 2005. We followed up the final sample until 2013 and evaluated the cumulative incidence of type 2 diabetes. We used extended Cox regression models to estimate the time-varying adjusted hazard ratios of statin use on new-onset type 2 diabetes. We performed further analyses based on the cumulative defined daily dose of statin received per year to evaluate the degree of risk compared to non-statin users. Results: Over the mean follow-up period of 7.1 years, 3034 patients developed type 2 diabetes; the number of statin users exceeded that of non-users, demonstrating that statin use significantly increased the risk of new-onset type 2 diabetes. The risk of new-onset type 2 diabetes differed among statin users according to cDDD per year (adjusted HR = 1.31 [95% CI 1.18-1.46] for less than 30 cDDD per year; 1.58 [1.43-1.75] for 30-120 cDDD per year; 1.83 [1.62-2.08] for 120-180 cDDD per year; and 2.83 [2.51-3.19] for more than 180 cDDD per year). The diabetogenic effect of pitavastatin was not statistically significant, but the risk was the largest for atorvastatin. Long-term exposure (≥ 5 years) to statins was associated with a statistically significant increase in the risk of new onset type 2 diabetes in all statin subtypes explored, with the highest magnitude for simvastatin (HR = 1.916, 95% CI 1.647-2.228) followed by atorvastatin (HR = 1.830, 95% CI 1.487-2.252). Conclusions: Statin use was significantly associated with an increased risk of new-onset type 2 diabetes. We also found a dose-response relationship in terms of statin use duration and dose maintenance. Periodic screening and monitoring for incident type 2 diabetes may be warranted in long-term statin users.

Association Between Triglyceride Glucose Index and Risk of New-Onset Diabetes Among Chinese Adults: Findings From the China Health and Retirement Longitudinal Study

“…Third, we could not differentiate statins and fibrates from lipid-lowering drugs from the information in CHARLS. The impact of statins treatment on the association between TyG index and diabetes was not fully addressed, considering that statins treatment might increase the risk of developing diabetes (35). Fourth, the follow-up time was relatively short.…”

Correspondence to proton pump inhibitors and risk of colorectal cancer

“…However, in the time since treatment initiation secondary analysis, the result showed that both short-term and long-term PPI usage have elevated CRC risk (HR 1.19, 95% CI 1.03 to 1.34), thereby conflicting with their conclusion. As a result, we suggest that the authors do a secondary analysis of time varying dose dependent model to further clarify the result and strengthen their conclusion 4…”

Impact of pitavastatin on new-onset diabetes mellitus compared to atorvastatin and rosuvastatin: a distributed network analysis of 10 real-world databases

“…Some studies have shown that pitavastatin did not adversely affect HbA1c level [ 13 , 38 ]. Recent retrospective study using the Korean insurance claims database reported that the risk of NODM was the largest for atorvastatin followed by rosuvastatin among individual statins when compared to non-statin users, but pitavastatin was not associated with increasing risk of NODM [ 39 ]. However, only 27 patients prescribed with pitavastatin were enrolled in that study.…”