Diabetes Metab J.  2021 Jul;45(4):505-514. 10.4093/dmj.2020.0057.

Cardiovascular Safety of Sodium Glucose Cotransporter 2 Inhibitors as Add-on to Metformin Monotherapy in Patients with Type 2 Diabetes Mellitus

Affiliations
  • 1Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea

Abstract

Background
Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea.
Methods
This was a retrospective observational study using the National Health Insurance Service claims database in Korea. The study period was from September 2014 to December 2016. The study included subjects who were newly prescribed SGLT2 inhibitors or other glucose-lowering drugs while on metformin monotherapy; cohort 1 was composed of new users of SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors and cohort 2 included new users of SGLT2 inhibitors versus sulfonylureas. To balance the patient characteristics, propensity score matching was performed at a 1:1 ratio. Cardiovascular outcomes included hospitalization for heart failure (HHF), all-cause mortality, HHF plus all-cause mortality, myocardial infarction (MI), stroke, and modified major adverse cardiovascular events (MACEs).
Results
After propensity score matching, each cohort group was well balanced at baseline (21,688 pairs in cohort 1 and 20,120 pairs in cohort 2). As the second-line treatment, use of SGLT2 inhibitors was associated with a lower risk of HHF and HHF plus all-cause mortality compared with DPP-4 inhibitors. In addition, use of SGLT2 inhibitors versus sulfonylurea as add-on therapy to metformin was associated with decreased risks of HHF, all-cause mortality, HHF plus all-cause mortality, MI, stroke, and modified MACEs.
Conclusion
SGLT2 inhibitors can be a good second-line drug to reduce the incidence of cardiovascular diseases compared with DPP-4 inhibitors or sulfonylureas in people with type 2 diabetes mellitus.

Keyword

Death; Diabetes mellitus; type 2; Heart failure; Myocardial infarction; Retrospective studies; Sodium-glucose transporter 2 inhibitors; Stroke

Figure

  • Fig. 1 Kaplan-Meier curves for cumulative incidence of cardiovascular outcomes. (A) Sodium glucose cotransporter 2 inhibitor (SGLT2i) versus dipeptidyl peptidase-4 inhibitor (DPP-4i). (B) SGLT2i versus sulfonylurea (SU). HF, heart failure; MACE, major adverse cardiovascular event; MI, myocardial infarction.

  • Fig. 2 Subgroup analyses for hospitalization for heart failure (HHF) and HHF plus all-cause death. HHF (A) and HHF and all-cause death (B) in comparison of sodium glucose cotransporter 2 inhibitor (SGLT2i) versus dipeptidyl peptidase-4 inhibitor (DPP-4i) and HHF (C) and HHF and all-cause mortality (D) compared between SGLT2i and sulfonylurea (SU). Hazard ratios (HRs) and 95% confidence intervals (CIs) for occurrence of cardiovascular events are presented for SGLT2i vs. DPP-4i or SU. CVD, cardiovascular disease; HF, heart failure; CKD, chronic kidney disease; DN, diabetic nephropathy; ASA, acetyl-salicylic acid.


Cited by  1 articles

Cardiovascular Safety of SGLT2 Inhibitors Compared to DPP4 Inhibitors and Sulfonylureas as the Second-Line of Therapy in T2DM Using Large, Real-World Clinical Data in Korea
Kyuho Kim, Sung Hee Choi
Diabetes Metab J. 2021;45(4):502-504.    doi: 10.4093/dmj.2021.0158.


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