Antihypertensives and the risk of serious hypoglycemia in older persons using insulin or sulfonylureas

JAMA. 1997 Jul 2;278(1):40-3.


Context: Beta-Blockers and angiotensin-converting enzyme (ACE) inhibitors are effective antihypertensive agents for patients with diabetes mellitus. However, beta-blockers attenuate some components of the autonomic response to hypoglycemia and could increase the risk of hypoglycemia. ACE inhibitors may increase insulin sensitivity and predispose users to hypoglycemia.

Objective: To determine whether use of cardioselective beta-blockers, nonselective beta-blockers, ACE inhibitors, thiazide diuretics, calcium channel blockers, or other antihypertensive drugs alters the risk of developing serious hypoglycemia among older persons prescribed insulin or sulfonylureas.

Design: Retrospective cohort study.

Setting: Tennessee Medicaid Program.

Patients: A total of 13,559 elderly (mean age, 78+/-7 years) Medicaid enrollees, who were prescribed insulin (n=5171, 38%) or sulfonylureas (n=8368, 62%) from 1985 through 1989. These enrollees contributed a total of 33,107 person-years of insulin or sulfonylurea use for follow-up.

Measurements: Hospitalization, emergency department admission, or death associated with hypoglycemic symptoms and a concomitant blood glucose determination of less than 2.8 mmol/L (50 mg/dL).

Results: We identified 598 persons with an episode of serious hypoglycemia during the study period. The rate of serious hypoglycemia was 2.01 per 100 person-years among those who were not prescribed antihypertensives. Crude rates of serious hypoglycemia were highest among users of ACE inhibitors (2.47 per 100 person-years) and lowest among users of cardioselective beta-blockers (1.23 per 100 person-years). However, when we controlled for demographic characteristics and markers of comorbidity, there was no statistically significant increase or decrease in risk of serious hypoglycemia among users of any class of antihypertensive agents compared with nonusers of antihypertensive drugs. Using nonselective beta-blockers as the reference group, each of these agents was associated with a lower, but not statistically significant, risk of hypoglycemia.

Conclusions: In this population, specific antihypertensive drug therapy had little impact on the risk of hypoglycemia in older diabetic patients. Therapy should be chosen based on other considerations of safety and effectiveness.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antihypertensive Agents / adverse effects*
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Cohort Studies
  • Diabetes Complications
  • Diabetes Mellitus / drug therapy*
  • Drug Interactions
  • Female
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypoglycemia / chemically induced
  • Hypoglycemia / etiology*
  • Insulin / pharmacology
  • Insulin / therapeutic use*
  • Male
  • Multivariate Analysis
  • Poisson Distribution
  • Regression Analysis
  • Retrospective Studies
  • Risk Factors
  • Sulfonylurea Compounds / pharmacology
  • Sulfonylurea Compounds / therapeutic use*


  • Antihypertensive Agents
  • Insulin
  • Sulfonylurea Compounds