Diuretics, statins associated with diabetes onset in high-risk patients

Starting a diuretic or a statin in patients with impaired glucose tolerance significantly increased their risk of developing diabetes, a study found.

Researchers reanalyzed data from the multinational Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. They looked at patients who started taking 1 or more of the drug classes for the first time during the study's 5-year follow-up: 915 patients on beta-blockers, 1,316 on diuretics, 1,353 on statins, and 1,171 on calcium-channel blockers (the metabolically neutral control group). Results were published by BMJ on Dec. 9.

After adjustment for baseline characteristics and time-varying confounders, a significant association with new-onset diabetes was found with diuretics (hazard ratio [HR], 1.23; 95% CI, 1.06 to 1.44) and statins (HR, 1.32; 95% CI, 1.14 to 1.46) compared to the group as a whole. Beta-blockers increased risk of diabetes by an insignificant amount (HR, 1.10; 95% CI, 0.92 to 1.31) and an insignificant decrease in risk was seen with calcium-channel blockers (HR, 0.95; 95% CI, 0.79 to 1.13).

The increase in diabetes found with diuretics and statins is similar to results from previous studies, the authors said, although the current study is larger and highlights the greater risk faced by patients with impaired glucose tolerance at baseline. According to their calculations, 1 additional case of diabetes would occur in 5 years for every 17 such patients given a diuretic and every 12 patients given a statin. Other studies have also shown an increase in diabetes with beta-blockers, and the trend toward an increase in risk found in this study is not inconsistent with that possibility. A larger sample size would be needed to detect an effect from beta-blockers, the authors said.

As an observational analysis, this study is limited by the risk of confounding, although the use of calcium-channel blockers as a control was meant to correct that, the authors noted. The data also did not include information on the specific drug within a class or dosage used, both of which have been previously shown to be factors in diabetes risk. The study's findings should be confirmed in prospective randomized trials, the authors said. In the interim, however, glycemia should be better monitored in patients with impaired glucose tolerance who are prescribed these drugs, they recommended.