Raj Padwal, MD
In older patients with type 2 diabetes, do thiazolidinediones (TZDs) increase risk for heart failure (HF), myocardial infarction (MI), and mortality more than other oral hypoglycemic agents?
Nested case–control study in a retrospective cohort study with a median follow-up of 3.8 years.
Population-based study in Ontario, Canada.
The cohort included 159 026 patients ≥ 66 years of age who had type 2 diabetes and had filled a prescription for ≥ 1 oral hypoglycemic agent (TZDs, metformin, sulfonylureas, or other agents) over a 3-year period. Patients who had received insulin in the preceding year were excluded, but those who started insulin during follow-up were not. Cases were patients who were hospitalized for HF (n = 12 491, mean age 77 y, 51% men) or MI (n = 12 578, mean age 77 y, 55% men) or who died (n = 30 265, mean age 79 y, 53% men) during follow-up. Controls (up to 5 per case) were randomly selected individuals who were event-free on the corresponding case's index date (date of first hospitalization or death) matched to cases by age, sex, diabetes duration, and history of cardiovascular disease.
Current or past (stopped in the year before the index date) use of TZDs (rosiglitazone or pioglitazone), as monotherapy or combined with other agents, compared with current other (non-TZD) oral hypoglycemic agent combination therapy (mainly metformin plus sulfonylurea).
Hospitalization for HF or MI, and all-cause mortality.
Current TZD monotherapy was associated with increased risk for HF, MI, and death (Table). Current TZD combination therapy and past treatment with TZDs were associated with increased risk for HF and death but not MI (Table). These adverse outcomes were associated only with rosiglitazone and not with pioglitazone, except for death in past TZD users, which was elevated with both drugs. With baseline event rates over 4 years of 9.5% for HF, 9.7% for MI, and 19% for death, the absolute risk increases with TZD were estimated at 3.0% for HF, 3.9% for MI, and 4.6% for death; numbers needed to harm were 34 (95% CI 21 to 52), 26 (CI 12 to 105), and 22 (CI 13 to 47), respectively.
In older patients with type 2 diabetes, thiazolidinediones (in particular, rosiglitazone) were associated with higher risks for heart failure, myocardial infarction, and mortality than other oral hypoglycemic agents.
Risk for heart failure, myocardial infarction, and death with thiazolidinediones (TZDs) compared with current combination therapy of other (non-TZD) oral hypoglycemic agents in older patients with type 2 diabetes
*CI defined in Glossary. Rate ratios were adjusted for other risk factors, including sociodemographic factors, comorbid conditions, and other drug use.
Padwal R. Thiazolidinediones increased risk for heart failure, myocardial infarction, and death in older patients with type 2 diabetes. Ann Intern Med. ;148:JC4–13. doi: 10.7326/0003-4819-148-12-200806170-02013
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Published: Ann Intern Med. 2008;148(12):JC4-13.
Acute Coronary Syndromes, Cardiology, Coronary Heart Disease, Coronary Risk Factors, Diabetes.
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