Association between antihypertensive drug use and hypoglycemia: A case-control study of diabetic users of insulin or sulfonylureas

Antihypertensive drugs are commonly prescribed for the treatment of patient s with both diabetes and hypertension. However, the role of selected agents in the development of hypoglycemia remains controversial. The main objecti ve of this study was to evaluate the effect of antihypertensive agents on t he risk of hypoglycemia in diabetic patients receiving insulin or sulfonylu rea therapy. A matched case-control study was conducted using Pennsylvania Medicaid data. Five control subjects, matched for sex and age, with no repo rted medical condition of hypoglycemia, were randomly selected for each cas e patient admitted for hypoglycemia in 1993, resulting in a total of 404 ca ses and 1375 controls. With these sample sizes, we were able to detect a di fference of 10% (P < 0.05) for our primary outcome measure, hospitalization for hypoglycemia. The relative risk of hypoglycemia was estimated using an unconditional logistic regression. The risk of hypoglycemia was 5.5 times greater (95% confidence interval [CI], 4.0 to 7.6) in insulin versus sulfon ylurea users and was not influenced by use of angiotensin-converting enzyme (ACE) inhibitors overall. However, use of the ACE inhibitor enalapril was associated with an increased risk of hypoglycemia (odds ratio, 2.4; 95% CI, 1.1 to 5.3) in sulfonylurea users, suggesting that analyzing the unintende d side effects of a class of drugs can sometimes mask the adverse effects o f individual drugs. Use of beta-blockers was not associated with an increas ed risk of hypoglycemia, providing further empiric evidence that beta-block ers are an appropriate treatment for persons with concomitant diabetes and hypertension. Per capita health care costs were similar to 3 times higher i n patients hospitalized for hypoglycemia compared with controls (P < 0.05). Hospitalization for hypoglycemia is expensive and may be prevented with ap propriate monitoring of diabetic patients taking selected antihypertensive agents such as enalapril.