Effect of statins on fasting glucose in non-diabetic individuals: nationwide population-based health examination in Korea

Abstract

BackgroundIncreasing evidence suggest that statin therapy has a diabetogenic effect. Individual types of statin may have a different effect on glucose metabolism. Using the repeated nationwide population-based health screening data in Korea, we investigated the longitudinal changes in fasting glucose level of non-diabetic individuals by use of statins.MethodsFrom the National Health Screening Cohort, we included 379,865 non-diabetic individuals who had ≥ 2 health screening examinations with fasting blood glucose level measured in 2002–2013. Using the prescription records of statins in the database, we calculated the proportion of days covered (PDC) and average number of defined daily doses per day (anDDD) by statins. We constructed multivariate linear mixed models to evaluate the effects of statins on the changes in fasting glucose (Δglu).ResultsHigh PDC by statins had a significant positive effect on Δglu (coefficient for PDC 0.093 mmol/L, standard error 0.007, p < 0.001). anDDD by statins was also positively associated with Δglu (coefficient for anDDD 0.119 mmol/L, standard error 0.009, p < 0.001). Unlike statins, the PDC by fibrate and ezetimibe were not significantly associated with Δglu. There was no significant interaction effect on Δglu between time interval and statin. Considering individual types of statins, use of atorvastatin, rosuvastatin, pitavastatin, and simvastatin were significantly associated with increase of Δglu. Pravastatin, lovastatin, and fluvastatin were also positively associated with Δglu, but were not statistically significant.ConclusionsMore adherent and intensive use of statins was significantly associated with an increase in fasting glucose of non-diabetic individuals. In subgroup analysis of individual statins, use of atorvastatin, rosuvastatin, pitavastatin and simvastatin had significant association with increase in fasting glucose. Pravastatin, lovastatin, and fluvastatin had non-significant trend toward an increased fasting glucose. Our findings suggest the medication class effect of statins inducing hyperglycemia.

Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet

“…Regarding the issue of statins and glucose level, Kim et al reported that use of atorvastatin, rosuvastatin, pitavastatin and simvastatin had a significant association with increase in fasting glucose of non-diabetic individuals [43]. However, Jeong et al reported that administration of highest-dose pitavastatin did not increase the risk of new-onset diabetes in patients at high risk of developing diabetes [44].…”

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

“…Considering the different pharmaco-epidemic responses and characteristics of diabetes in Asians, the risk of new-onset diabetes following long-term statin use is likely to be heterogeneous among Asians. Furthermore, most previous studies on Asians have only used a single hospital center or health screening data that lacked external validity [11,12,[34][35][36].…”

Combination Therapy with Pemafibrate (K-877) and Pitavastatin Improves Vascular Endothelial Dysfunction in Dahl/Salt-sensitive Rats Fed a High-salt and High-fat Diet​

“…Regarding the issue of statins and glucose level, Kim et al reported that use of atorvastatin, rosuvastatin, pitavastatin and simvastatin had a signi cant association with increase in fasting glucose of nondiabetic individuals [43]. However, Jeong et al reported that administration of highest-dose pitavastatin did not increase the risk of new-onset diabetes in patients at high risk of developing diabetes [44].…”