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October 30, 2020Diabetes & Metabolism JournalOpen Access

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

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Key result

SGLT2 inhibitors added to metformin monotherapy were associated with a 22% lower risk of hospitalization for heart failure compared to DPP-4 inhibitors (HR 0.78).

Why the study?

Real-world cardiovascular safety needed investigation in patients with type 2 diabetes mellitus newly starting SGLT2 inhibitors compared with other glucose-lowering drugs as add-on to metformin monotherapy.

Does the addition of SGLT2 inhibitors to metformin monotherapy reduce the risk of cardiovascular events compared to DPP-4 inhibitors or sulfonylureas in patients with type 2 diabetes mellitus?

Population

Patients with type 2 diabetes mellitus on metformin monotherapy in Korea (21,688 pairs in cohort 1; 20,120 pairs in cohort 2)

Comparison

SGLT2 inhibitors vs DPP-4 inhibitors (cohort 1) and vs sulfonylureas (cohort 2)

Design

Retrospective propensity score-matched observational study

Authors

JJJa Young JeonKHKyoung Hwa HaDKDae Jung Kim

Discussion

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Overview

May support CV safety of SGLT2 inhibitors in Korean metformin users; hypothesis-generating and requires randomized confirmation before practice change.

Study Design

Type

Cohort (n=83,616)

Structured PICO

Does the addition of SGLT2 inhibitors to metformin monotherapy reduce the risk of cardiovascular events compared to DPP-4 inhibitors or sulfonylureas in patients with type 2 diabetes mellitus?

P
Population
83,616 propensity-score matched adults with type 2 diabetes on metformin monotherapy newly starting an SGLT2 inhibitor, DPP-4 inhibitor, or sulfonylurea, followed for a median of 333 to 354 days.
E
Exposure
SGLT2 inhibitors (dapagliflozin, empagliflozin, or ipragliflozin) added to metformin monotherapy.
C
Comparator
Cohort 1: Dipeptidyl peptidase-4 (DPP-4) inhibitors added to metformin monotherapy. Cohort 2: Sulfonylureas added to metformin monotherapy.
O
Outcome
Cardiovascular outcomes including hospitalization for heart failure (HHF), all-cause mortality, HHF plus all-cause mortality, myocardial infarction (MI), stroke, and modified major adverse cardiovascular events (MACEs; defined as all-cause mortality, MI, and stroke).hard clinical

Main Result

Hazard Ratio: 0.78 (95% CI 0.63–0.97)

Absolute Event Rate: 0.69% vs 0.89%

p-value: p=0.024

In a real-world Korean cohort, adding SGLT2 inhibitors to metformin monotherapy in patients with type 2 diabetes was associated with significantly lower risks of heart failure hospitalization compared to adding DPP-4 inhibitors or sulfonylureas.

Limitations

  • Undetected and residual confounding by indication could have existed despite performing propensity score matching
  • The claim database does not include information regarding the duration of diabetes, laboratory findings, or health behavior
  • Individual drugs within the same class may show different results
  • Longer time effects could not be assessed because SGLT2 inhibitors were recently introduced in clinical practice
  • Undetected and residual confounding by indication despite propensity score matching
  • Lack of information regarding the duration of diabetes, laboratory findings, or health behavior in the claims database
  • Longer time effects could not be assessed because SGLT2 inhibitors were recently introduced

Cite This Study

Jeon et al. (2020) conducted a cohort in Type 2 Diabetes Mellitus (n=83,616). SGLT2 inhibitors vs. DPP-4 inhibitors was evaluated on Hospitalization for heart failure (HHF) (HR 0.78, 95% CI 0.63-0.97, p=0.024). SGLT2 inhibitors added to metformin monotherapy were associated with a 22% lower risk of hospitalization for heart failure compared to DPP-4 inhibitors (HR 0.78).

synapsesocial.com/papers/6a7772fadf493903fd1ef002https://doi.org/10.4093/dmj.2020.0057
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