FC 125: Comparative Effectiveness of Dipeptidyl Peptidase-4 Inhibitors versus Sulfonylureas in Addition to Metformin: A Population-Based Cohort Study of Patients With Diabetes
Authors: Wu Hon-Yen , Wang Jui , Chien Kuo-Liong 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Effects of dipeptidyl peptidase-4 inhibitors (DPP4i) versus sulfonylureas (SU) in addition to metformin remain controversial in patients with type 2 diabetes. Some studies have shown that DPP4i provided cardioprotective effects, but some have reported that DPP4i showed neutral effects on cardiovascular outcomes. In addition, randomized clinical trials have reported inconsistent effects on heart failure among different types of DPP4i. This study aimed to clarify the conflicting cardiovascular effects of DPP4i and examine whether class effects exist among different types of DPP4i.

METHOD
We conducted a nationwide cohort study using claims data from the National Health Insurance in Taiwan from 2007 to 2013. We enrolled type 2 diabetes patients who received DPP4i or SU in addition to metformin. Participants who received DPP4i for at least three consecutive months were categorized as DPP4i users, and those who received SU for at least three consecutive months were categorized as SU users. DPP4i users were matched to SU users using propensity scores at a ratio of 1:1. The study outcomes were hospitalization for major adverse cardiovascular events (MACEs), heart failure, acute myocardial infarction, cerebrovascular disease, coronary revascularization and hypoglycemia. Univariate and multivariate Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for study outcomes comparing DPP4i with SU.

RESULTS
There were 37 317 matched pairs of DPP4i and SU users with a mean follow-up of 2.1 years. Compared with SU users, DPP4i users showed a significantly lower risk of hospitalization for MACE (HR 0.79, 95% CI 0.75–0.82), heart failure (HR 0.86, 95% CI 0.79–0.93), acute myocardial infarction (HR 0.79, 95% CI 0.68–0.92) and cerebrovascular disease (HR 0.72, 95% CI 0.67–0.77) (Table 1). Both sitagliptin and vildagliptin showed significantly lower risks of hospitalization for MACE (sitagliptin: adjusted HR 0.89, 95% CI 0.85–0.94; vildagliptin: adjusted HR 0.77, 95% CI 0.60–0.99) and cerebrovascular disease (sitagliptin: adjusted HR 0.81, 95% CI 0.75–0.88; vildagliptin: adjusted HR 0.64, 95% CI 0.44–0.92) (Figure 1). All three types of DPP4i users showed a significantly lower risk of hospitalization for hypoglycemia (sitagliptin: adjusted HR 0.45, 95% CI 0.39–0.52; vildagliptin: adjusted HR 0.22, 95% CI 0.09–0.52; saxagliptin: adjusted HR 0.38, 95% CI 0.17–0.83), but saxagliptin showed a borderline significantly higher risk of hospitalization for heart failure (HR 1.59, 95% CI 1.00–2.55).

CONCLUSION
DPP4i showed better protective effects than SU in outcomes of MACE, heart failure, acute myocardial infarction, cerebrovascular disease and hypoglycemia. Sitagliptin and vildagliptin showed more prominent protective effects. Compared with SU, all three types of DPP4i lowered the risk of hypoglycemia in patients with type 2 diabetes.