Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study

Abstract

AimTo compare the risks of hospitalization for heart failure (HHF) associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP-4i), and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy using the data of Korean adults with type-2 diabetes from the Korean National Health Insurance database.MethodsWe identified 98,383 people who received SU (n = 42,683), DPP-4i (n = 50,310), or TZD (n = 5,390) added to initial treatment of MET monotherapy in patients with type-2 diabetes. The main outcome was the hospitalization for HHF. Hazard ratios for HHF by type of second-line glucose-lowering medication were estimated by Cox-proportional hazard models. Sex, age, duration of MET monotherapy, Charlson Comorbidity Index and additional comorbidities, and calendar year were controlled as potential confounders.ResultsThe observed numbers (rate per 100,000 person-years) of HHF events were 1,129 (658) for MET+SU users, 710 (455) for MET+DPP-4i users, and 110 (570) for MET+TZD users. Compared to that for MET+SU users (reference group), the adjusted hazard ratios for HHF events were 0.76 (95% confidence interval 0.69–0.84) for MET+DPP-4i users and 0.96 (95% confidence interval 0.79–1.17) for MET+TZD users.ConclusionDPP-4i as an add-on therapy to MET may lower the risks of HHF compared with SU.

Cardiovascular Outcomes and the Use of Oral Antidiabetic Drugs: A Review of Current Evidence from Observational Studies

“…8 Regarding the sample size included, one-third of the total studies were designed as nationwide and population-based studies. [9][10][11][12][13][14][15][16] The findings of the included studies show that conventional ADDs, like metformin and S.U., were present in almost more than half of the comparisons with other ADD monotherapies. A relatively fewer number of studies were reported for SGLT2i, where only three studies investigated its associated CV outcomes.…”

“…added to metformin conferred a higher risk of hospital hospitalisation compared to the DPP4i added to metformin. 16 Also, as monotherapies, DPP4i a safer ADD to be offered to diabetic patients with H.F. compared to glimepiride. 27 In a retrospective Korean cohort study, the findings suggested that Asian diabetic patients could have higher benefits, such as achieving average baseline blood glucose in patients with lower body mass index, by using DPP4i relative to other ethnic groups.…”

“…Hence, concerning this issue, TZD might not be a preferred ADD for patients at high risk of H.F. hospitalization. 16 Furthermore, in a retrospective cohort study conducted in the UK to compare the CV risk of ADD added to metformin therapy, TZD showed a significantly lower CVD risk and death compared to S.U. Whereas DPP4i showed a trend of a statistically insignificant lower risk.…”

Is it time to ban sulfonylureas?

“…In a retrospective cohort study in China, SUs monotherapy was significantly associated with a higher risk of heart failure compared with acarbose monotherapy for initial treatment of T2DM 6 . More evidence was seen in the Korean adults with T2DM, SU as an add‐on therapy to metformin may increase the risks of heart failure compared with dipeptidyl peptidase‐4 (DPP‐4) inhibitors 7 …”

Effect of Teneligliptin versus Sulfonylurea on Major Adverse Cardiovascular Outcomes in People with Type 2 Diabetes Mellitus: A Real-World Study in Korea

“…In a recent meta-analysis with randomized controlled trials and observational studies, the use of DPP-4 inhibitors was not associated with increased risk of CV outcomes, including HHF, compared to the control group [ 9 ]. However, in a recent observational study with a nationwide database, the use of DPP-4 inhibitors as an add-on therapy to metformin was associated with a higher risk of HHF compared to sulfonylurea [ 10 ], while other studies have demonstrated that the use of DPP-4 inhibitors was associated with a lower risk of cardiovascular disease (CVD) events, including HHF, compared to the use of sulfonylurea [ 11 , 12 ].…”