Pioglitazone added to insulin increases ischemic heart disease risk in type 2 diabetes
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Key takeaways:
- Patients with metformin-uncontrolled type 2 diabetes taking insulin and pioglitazone had greater risk for ischemic heart disease.
- Older patients and men had greater risk for ischemic heart disease.
Patients with type 2 diabetes uncontrolled by metformin who received pioglitazone and insulin demonstrated increased risk for ischemic heart disease, according to findings published in the Journal of Diabetes and Its Complications.
Patients with type 2 diabetes who do not respond to first-line metformin may be prescribed oral diabetes drugs. However, these medications may increase cardiovascular risk, which is already greater in patients with type 2 diabetes.
“No recent studies have examined the risk of ischemic heart disease associated with different second-line oral anti-diabetic drugs added after patients with type 2 diabetes were uncontrolled on metformin,” Hsin-An Lin, with the division of infection in the department of medicine at the Tri-Service General Hospital Songshan Branch at the National Defense Medical Center in Taipei City, Taiwan, and colleagues wrote.
Researchers performed a nationwide cohort study to investigate risk for ischemic heart disease (IHD) associated with use of pioglitazone, a thiazolidinedione, with or without insulin, among patients with type 2 diabetes uncontrolled by metformin.
The researchers used the National Health Insurance Research Database of Taiwan to evaluate data from 19,952 patients aged 18 years or older with uncontrolled type 2 diabetes who had received first-line metformin. The researchers divided these participants into four matched groups (n = 4,998) based on whether they received pioglitazone plus insulin, pioglitazone alone, insulin alone or neither.
The primary endpoint of the study was IHD, which included acute myocardial infarction, acute and subacute forms of IHD, angina and chronic IHD. Patients were monitored from 2000 to incidence of IHD or 2015.
Overall, cumulative incidence of IHD was greatest in the pioglitazone-insulin group (15.48%), followed by the pioglitazone-alone group (13.59%), the insulin-alone group (12.73%) and the neither-nor group (8.64%).
The data suggested that patients taking both pioglitazone and insulin were 1.9 times (adjusted HR = 1.91; 95% CI, 1.51-2.35) more likely to develop IHD compared with those not on either medication. Risk for IHD was approximately 1.4 times greater for the pioglitazone-alone group (aHR = 1.45; 95% CI, 1.11-1.78) and the insulin-alone group (aHR = 1.35; 95% CI, 1.11-1.68).
Results also showed that men (aHR = 2.86; 95% CI, 1.28-4.01), older patients (age 45-64 years, aHR = 1.56; 95% CI, 1.07-2.16; age 65 years, aHR = 1.76; 95% CI, 1.33-2.37) and patients with comorbidities such as hyperlipidemia (aHR = 2.05; 95% CI, 1.27-2.37) or chronic kidney disease (aHR = 2.99; 95% CI, 1.65-3.92) were at greater risk for IHD.
The data were supported by regression analyses adjusted for sex, age, insurance premium and health factors.
The researchers also found that pioglitazone plus insulin increased risk for IHD compared with pioglitazone alone (aHR = 1.32; 95% CI, 1.03-1.56) or insulin alone (aHR = 1.41; 95% CI, 1.08-2), according to Cox regression analyses.
Also, a higher cumulative defined daily dose of pioglitazone plus insulin increased IHD risk compared with lower doses.
Lin and colleagues noted several limitations to the study, including the potential for unmeasured cofounding variables and their lack of information concerning medication compliance.
“Given the risk of IHD enhanced by pioglitazone combined with insulin shown in the present study, we suggest that the use of pioglitazone combined with insulin after first-line metformin should be minimized in patients with type 2 diabetes,” the researchers wrote. “Other second-line anti-diabetes agents may be a better option, including SGLT2 inhibitors, GLP-1 receptor agonists and DPP-IV inhibitors.”
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