Adding sulfonylureas to first-line metformin treatment may be a safer option than switching to sulfonylureas entirely in patients with type 2 diabetes, according to new findings.
Researchers arrived at this conclusion after conducting a study of 77,138 patients with type 2 diabetes who had initiated metformin monotherapy between 1998 and 2013. Mean follow-up lasted 1.1 years.
Patients continuing metformin monotherapy were matched 1:1 with patients adding sulfonylureas to metformin therapy or switching to second-line therapy with sulfonylureas. Matches were based on high-dimensional propensity score, hemoglobin A1c (HbA1c), and number of previous metformin prescriptions.
Adjusted hazard ratios (HRs) and 95% confidence intervals for each outcome were compared between groups via Cox proportional hazards models.
In this cohort, 25,699 of 77,138 participants added or switched to sulfonylureas. Compared with continuing metformin monotherapy, sulfonylurea treatment was associated with an elevated risk for:
- Myocardial infarction (MI; incidence rate 6.2 vs 7.8 per 1000 person-years; HR 1.26)
- All-cause mortality (incidence rate 21.5 vs 27.3 per 1000 person-years; HR 1.28)
- Severe hypoglycemia (incidence rate 0.7 vs 5.5 per 1000 person-years; HR 7.60)
In addition, the researchers observed a trend towards increased risks for ischemic stroke (6.7 vs 5.5 per 1000 person-years; HR 1.24) and cardiovascular (CV) death (9.4 vs 8.1 per 1000 person-years; HR 1.18) among sulfonylurea users compared with metformin users.
Switching to sulfonylureas entirely was tied to a higher risk for MI (HR 1.51) and all-cause mortality (HR 1.23) compared with adding sulfonylureas to metformin monotherapy. However, no between-group differences were noted for ischemic stroke, CV death, or severe hypoglycemia.
“Sulfonylureas as second line drugs are associated with an increased risk of myocardial infarction, all-cause mortality, and severe hypoglycemia, compared with remaining on metformin monotherapy,” the researchers concluded. “Continuing metformin when introducing sulfonylureas appears to be safer than switching.”
Douros A, Dell’Aniello S, Yu OHY, Filion KB, Azoulay L, Suissa S. Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycemic events: population based cohort study [Published online July 18, 2018]. BMJ. https://doi.org/10.1136/bmj.k2693