Statins And The Risk of Developing Diabetes

Recent studies have shown that statins can raise blood sugar and more patients on statin therapy were diagnosed with diabetes mellitus.

Elevated baseline serum glucose and insulin concentrations might be explained by a diabetogenic effect of statins. Some potential underlying mechanisms for this effect in diabetes-free individuals consist of decreased insulin-mediated cellular glucose uptake leading to glucose intolerance, decreased isoprenoids synthesis, which causes downregulation of glucose transporter 4 and leads to hyperglycemia and hyperinsulinemia, and reduced factors such as coenzyme Q10, farnesyl pyrophosphate, and dolichol leading to altered insulin secretion/resistance.

In a systemic review and network meta-analysis by D. Thakker et al that was performed to update evidence regarding the association between statins and diabetes. The direct meta-analysis showed that statins, as a class, significantly increased the likelihood of developing diabetes by 12%. In the network meta-analysis, Atorvastatin 80 mg was associated with a highest risk of diabetes, followed by Rosuvastatin. High-dose atorvastatin increased the odds of developing diabetes even when compared with pravastatin, simvastatin and low-dose atorvastatin in the network meta-analysis.

The study concluded that overall, there appears to be a small increased risk of incident diabetes, particularly with more intensive statin therapy, although more data would be valuable to increase the robustness of this interpretation.

In a recent study by F. Ahmadizar et al, researchers aimed to assess the population-based association of statins with concentrations of serum fasting glucose and insulin, insulin resistance, and incident type 2 diabetes, where they explored different aspects of statin therapy, including type, dosages and durations of use. They hypothesized that statins have influence on serum blood glucose and insulin concentrations and insulin resistance, and lead to hyperglycemia and hyperinsulinemia as early markers of type 2 diabetes.

Using the prospective population-based Rotterdam Study, they included 9,535 individuals free from diabetes at baseline (>45 years) during the study period between 1997 and 2012. Linear regression analysis was applied to examine the cross-sectional associations between statin use and glycemic traits, including fasting blood serum of glucose and insulin concentrations, and insulin resistance. In a longitudinal follow-up study, they applied a Cox regression analysis to determine adjusted hazard ratios (HR) for incident type 2 diabetes in new users of statins.

At baseline, statin use was associated with elevated values for several glycemic traits. After excluding these baseline statinusers, new ever statin users during a follow-up of up to 15 years showed a 38% increased risk of incident type 2 diabetes independent of statin type and dosage. All observed associations between statin use and incident type 2 diabetes remained significant even after adjusting for several potential risk factors for diabetes, e.g. age, physical activity, and education level. However, there was a steep decrease in the effect estimates corresponding to the adjusted models.

The study showed that the association between statin therapy and incident type 2 diabetes was partly dependent on lipid profiles, including HDL-C, LDL-C and TG, though independent of several diabetes risk factors such as hypertension. Moreover, the result of the interaction between statin use and serum fasting glucose concentrations was highly significant implying the greatest statin-associated diabetes risk in presence of baseline impaired glucose concentrations.

The study concluded that there was consistent significant association between statin use and incident type 2 diabetes. The analysis also highlighted the greatest effect of statins in the presence of hyperglycemia and overweight/obesity. This suggests that it is necessary to take statin diabetogenicity into consideration in clinical practice when statin is indicated, emphasizing the concomitant need for dietary measures and exercise.

Practice Pearls:

• Individuals on statins may be at higher risk for hyperglycemia, insulin resistance, and eventually type 2 diabetes.
• Studies suggest that statins may have a diabetogenic effect through beta-cell dysfunction and glucose and insulin secretion/sensitivity.
• Rigorous preventive strategies such as glucose control and weight reduction in patients when initiating statin therapy might help in minimizing the risk of diabetes.

References:

Ahmadizar F, OchoaRosales C, Glisic M, Franco OH, Muka T, Stricker BH. Associations of statin use with glycaemic traits and incident type 2 diabetes. Br J Clin Pharmacol. 2019 Mar 5.

Thakker D, Nair S, Pagada A, Jamdade V, Malik A. Statin use and the risk of developing diabetes: a network meta-analysis. Pharmacoepidemiol Drug Saf. 2016 Oct;25(10):1131-1149.

Dahlia Elimairi, Pharm D Student, UC Denver Skaggs School of Pharmacy