JMIR Publications

ABSTRACT

Background:

Patients with type 2 diabetes mellitus (T2D) have a higher risk of cardiovascular disease, including heart failure (HF), leading to healthcare burden including hospitalization and mortality. Among multiple T2D therapies, there are inadequate head-to-head comparisons of their effects on HF over real-world patient population.

Objective:

This study aims to compare time to heart failure among patients treated with different T2D drugs following metformin.

Methods:

We conducted a retrospective data analysis on electronic health records (EHRs) of 5,000 T2D patients. Inclusion criteria included previously treated with metformin and initiated T2D medications under any of the 4 mechanisms: glucagon-like peptide-1 analogues (GLP-1), Dipeptidyl Peptidase-4 inhibitors (DPP-4), sulfonylureas or insulin. We grouped patients by the mechanism of their second line therapies and focused on two pairs of comparisons classified by insulin resistance: sulfonylureas vs insulin (increase resistance) and GLP-1 vs DPP-4 (decrease resistance). The outcomes were 5-year HF status and the HF-free survival time, which was verified manually by examining clinical notes. We applied doubly robust causal estimation and accounted for confounding by adjusting for coded and natural language processing EHR features identified through medical knowledge networks.

Results:

The study included 939 patients, of whom 204 received insulin, 482 received sulfonylureas, 90 received GLP-1 and 163 received DPP-4. Patients in the sulfonylureas group had significantly higher 5-year HF-free survival compared to the insulin group (survival ratio of insulin/ sulfonylureas 0.902, 95% CI 0.840 – 0.976, p-value .01). There was no significant difference between DPP-4 vs GLP-1 group in 5-year HF-free survival (survival ratio of GLP-1/ DPP-1 0.953, 95% CI 0.849 – 1.067, p-value .40). For the occurrence of a HF-related hospitalization within 5 years, there were no significant differences between the sulfonylureas and insulin (risk difference insulin - sulfonylureas 0.057, 95% CI -0.011 – 0.132, p-value .11), and between the GLP-1 and DPP-4 (risk difference GLP-1 – DPP-4 0.010, 95% CI -0.096 – 0.129).

Conclusions:

We evaluated real-world evidence on two head-to-head comparisons of 2nd line T2D therapies on 5-year HF outcomes. Patients on sulfonylureas as second-line T2D therapy had significantly lower 5-year HF risks than those treated with insulin when measured by risk ratio, but no significant difference was detected when measured by the risk difference. Limitation included potentially inadequate adjustment of confounding in the observational study, and limited sample size with validated HF outcomes.