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Incidence of Diabetes with Statin Use

Diabetes increased modestly in general.

Payal Kohli, M.D., from Kaiser Permanente in Denver, and colleagues conducted a retrospective analysis of data from subjects without diabetes in the Treating to New Targets (TNT) and Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trials to identify increased risk of statin-associated T2DM.

Diabetogenic impact of statins increases as fasting plasma glucose, triglycerides, and BMI increase.

Participants were subdivided into four groups: normal fasting glucose (NFG) and triglyceride (TG) ≤1.7 mmol/L; NFG and TG >1.7 mmol/L; prediabetes mellitus (PreDM) and TG ≤1.7 mmol/L; and PreDM and TG >1.7 mmol/L. Comparable groupings were created by substituting body mass index (BMI) values for TG concentration (<27.0 and ≥27.0 kg/m²).

The researchers found that 8.2 percent of the total population developed incident T2DM. There was variation in T2DM event rates (statin or placebo), from a low of 2.8 percent/3.2 percent (NFG and TG ≤1.7 mmol/L) to a high of 22.8 percent/7.6 percent (PreDM and TG >1.7 mmol/L); the values were intermediate for only elevated TG >1.7 mmol/L (5.2 percent /4.3 percent) or only PreDM (12.8 percent/7.6 percent). The differences were comparable with BMI values.

Statins are associated with significantly reducing the risk for cardiovascular events when used as either primary or secondary prevention. The association of statins with the risk for incident diabetes is less well understood, but in an earlier study, previous meta-analysis of 13 clinical trials of statins featuring a total of 91,140 patients suggests that the risk for diabetes associated with these medications is real. This earlier research found that the use of statins was associated with a 9% increased risk for diabetes, with little heterogeneity among the trials. The risk for diabetes associated with statins was particularly profound for older adults, although body mass index and the efficacy of the statin on lipid values did not alter this result. Nonetheless, the authors of the study calculate a high number needed to harm in terms of the risk for diabetes with statin therapy. A total of 255 patients receiving statins for four years would produce one additional case of diabetes.

The diagnosis of diabetes in this previous research was based on fasting plasma glucose levels or clinician diagnosis, but other studies linking statins with the risk for diabetes have used even less stringent criteria to identify diabetes.  So for this study, statin therapy appears to increase the risk for type 2 diabetes by 46%, even after adjustment for confounding factors, a large new population-based study concludes.

This suggests a higher risk for diabetes with statins in the general population than has previously been reported, which has been in the region of a 10% to 22% increased risk.

The majority of people in this new study were taking atorvastatin and simvastatin, and the risk for diabetes was dose dependent for these 2 agents, the researchers found.

In one other study, the authors investigated the effects of statin treatment on blood glucose control and the risk for type 2 diabetes in 8,749 nondiabetic men 45 to 73 years old in a 6-year follow-up of the population-based Metabolic Syndrome in Men trial.  The authors also investigated the mechanisms of statin-induced diabetes by evaluating changes in insulin resistance and insulin secretion.  During the follow-up, 625 of the participants were diagnosed with diabetes. Indices derived from oral glucose tolerance tests were used to assess insulin sensitivity and secretion.

A total of 2,412 individuals were taking statins. The drugs were associated with an increased risk for type 2 diabetes even after adjustment for age, body mass index, waist circumference, physical activity, smoking, alcohol intake, a family history of diabetes, and beta-blocker and diuretic treatment. The risk was found to be dose dependent for simvastatin and atorvastatin, which were taken by 388 and 1,409 participants, respectively.

Statin therapy was also associated with a significant increase in 2-hour glucose and the glucose area under the curve at follow-up, as well as a nominally significant increase in fasting plasma glucose levels.

Furthermore, individuals taking statins had a 24% decrease in insulin sensitivity and a 12% reduction in insulin secretion compared with those not receiving the drugs. These increases were again dose dependent for atorvastatin and simvastatin.

Markku Laakso, MD, from the University of Eastern Finland and Kuopio University Hospital, added that, “Even if statin treatment is increasing the risk of getting diabetes, statins are very effective in reducing cardiovascular risk.”

Dr. Laakso added that, “The takeaway message from these studies is that people should not stop statin treatment, especially those patients who have a history of myocardial infarction…. But what I would say is that people who are at the higher risk, if they are obese, if they have diabetes in the family, etc., should try to lower their statin dose, if possible, because high-dose statin treatment increases the risk vs lower-dose statin treatment.”

Practice Pearls:

  • Individuals taking statins had a 24% decrease in insulin sensitivity and a 12% reduction in insulin secretion compared with those not receiving the drugs.
  • A total of 255 patients receiving statins for four years would produce one additional case of diabetes.
  • If statin treatment is increasing the risk of getting diabetes, statins are very effective in reducing cardiovascular risk.

The American Journal of Cardiology, Nov 2016: Diabetologia. 2015;58:1109-1117. Abstract.