Second-line therapies for type 2 diabetes may offer similar glycemic control

The only significant difference found by the meta-analysis was a small increase in myocardial infarction and eye disorders with sulfonylureas compared with dipeptidyl peptidase-4 inhibitors.


A meta-analysis of second-line treatment options for patients with type 2 diabetes found that sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and thiazolidinediones did not significantly differ in their ability to lower HbA1c level, although sulfonylureas were associated with a small increased risk of myocardial infarction and eye disorders compared with DPP-4 inhibitors.

Researchers used the Observational Health Data Sciences and Informatics network to retrospectively analyze data from more than 246 million patients from cohort studies conducted from 1975 to 2017. Participants had type 2 diabetes, were taking metformin, and had at least one HbA1c test before being prescribed sulfonylureas, DPP-4 inhibitors, or thiazolidinediones at least 90 days after the initial prescription of metformin.

The primary outcome was reduction of HbA1c level to 7% or less after prescription of a second-line drug. Secondary outcomes were myocardial infarction, kidney disorder, and eye disorder after prescription of a second-line agent. Results were published online on Aug. 24 by JAMA Network Open.

The researchers analyzed a total of 246,558,805 patients (51.5% women). Overall, sulfonylureas, DPP-4 inhibitors, and thiazolidinediones did not differ in consensus hazard ratio (HR) estimates for lowering HbA1c level to 7% or less (0.99 [95% CI, 0.89 to 1.10] for sulfonylureas vs. DPP-4 inhibitors, 1.06 [95% CI, 0.96 to 1.16] for sulfonylureas vs. thiazolidinediones, and 1.08 [95% CI, 0.96 to 1.21] for DPP-4 inhibitors vs. thiazolidinediones).

For the secondary outcomes, there was a small but significant increase in myocardial infarction (HR, 1.12; 95% CI, 1.02 to 1.24) and eye disorders (HR, 1.15; 95% CI, 1.11 to 1.19) with sulfonylureas compared with DPP-4 inhibitors. The results of other comparisons were not significant, and the risk for kidney disorders after treatment was equally likely across the drug classes.

The study authors noted limitations, such as potential data quality issues within the large health care databases used, as well as the possibility of unmeasured confounding. They added that there was considerable heterogeneity in HbA1c reduction across study sites.

Given the small increased risk of myocardial infarction and eye disorders with sulfonylureas, “Our findings support preferring DPP-4 inhibitors over sulfonylureas as second-line therapies, in agreement with the February 2017 recommendation from the American Association of Clinical Endocrinologists and American College of Endocrinology, which did not inform our study given the timing and the date ranges of the data sets used,” the authors wrote.