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April 3, 2026Cardiovascular Diabetology – Endocrinology Reports0 citationsOpen Access

Effects of empagliflozin on cardiac function and cardiorespiratory fitness in people with type 2 diabetes: a randomised controlled trial

NNNatalie NanayakkaraMHMichael L. H. HuangAGAndre La Gerche

Key Result

Empagliflozin significantly reduced resting left ventricular end-diastolic volume by 9.51 mL compared to placebo in adults with type 2 diabetes, but did not improve peak oxygen consumption.

Key Points

  • The aim is to evaluate the impact of empagliflozin on cardiac function and cardiorespiratory fitness in individuals with type 2 diabetes.
  • Double-masked, single-centre, randomised, placebo-controlled trial
  • Participants were adults with type 2 diabetes mellitus
  • Intervention involved empagliflozin 25 mg daily vs. placebo for three months
  • Cardiac function assessed via echocardiography and cardiorespiratory fitness measured with a peak exercise test
  • 65 participants recruited, with 57 completing the study
  • No significant change in VO2 peak between empagliflozin and placebo groups
  • Empagliflozin reduced left ventricular end-diastolic volume by 9.51 mL compared to a 2.13 mL increase in placebo (p = 0.0232)
  • Despite no improvement in VO2 peak, empagliflozin may increase cardiovascular efficiency.

Study Design

Type

RCT (n=65)

Blinding

Double-blind

Randomization

1:1

Multicenter

No

Structured PICO

Does empagliflozin 25 mg daily improve change in VO2 peak in adults with type 2 diabetes mellitus?

P
Population
Adults (≥ 18 years) with type 2 diabetes mellitus without established heart failure
I
Intervention
Empagliflozin 25 mg daily
C
Comparator
Matching placebo
O
Outcome
Change in cardiorespiratory fitness (CRF) as reflected by VO2 peaksurrogate

In adults with type 2 diabetes, 12 weeks of empagliflozin significantly reduced left ventricular end-diastolic volume but did not improve cardiorespiratory fitness (VO2 peak).

Main Result

Absolute Event Rate: -63.09% vs -0.03%

p-value: p=>0.050

Limitations

  • Relatively short duration (12 weeks)
  • Multiple echocardiography parameters examined raising possibility of chance findings
  • Single-centre design
  • Modest sample size
  • Exclusion of patients with advanced cardiac dysfunction
  • COVID-19 pandemic posed substantial challenges to recruitment and participant retention
  • Short treatment timeframe (12 weeks) may not be sufficient to manifest VO2 peak improvements

Abstract

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in adults with type 2 diabetes mellitus (T2DM). Cardiac dysfunction and decreased exercise capacity are common in people with T2DM, even in those without overt heart failure. Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, reduces major cardiovascular events and mortality in people with T2DM and established CVD, though the underlying mechanisms are not fully elucidated. This study aimed to assess changes in cardiac function and cardiorespiratory fitness (CRF) at rest and during exercise with empagliflozin treatment in people with T2DM. This double-masked, single-centre, randomised, placebo-controlled analysis combined two studies involving adults (≥ 18 years) with T2DM comparing empagliflozin 25 mg daily vs. placebo, each over three months. VO₂ peak was measured using a ramp protocol peak exercise test on a bicycle ergometer, and echocardiography assessed changes in cardiac structure and function. Of 65 recruited participants, 57 completed the study (70.2% male, age 64.9 ± 7.8 year, baseline HbA1c 7.8% (7.5–8.4). Thirty-one participants (67.7% male, age 65.6 ± 6.6 year) were randomised to the placebo group, and 26 participants (73.1% male, age 64.2 ± 9.0 year) were randomised to empagliflozin. No significant between-group difference in the primary outcome of change in VO2 peak was observed. Empagliflozin reduced left ventricular end-diastolic volume (LVEDV) at rest by 9.508 ± 14.54 mL compared with placebo, which increased by 2.13 ± 20.73 mL (p = 0.0232). In adults with T2D, 12 weeks of empagliflozin significantly reduced LVEDV without changing VO2 peak. Empagliflozin may enhance cardiovascular efficiency without directly improving functional capacity. ACTRN12617000490370p & ACTRN12619000887178.

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Cite This Study

Nanayakkara et al. (2026) conducted an RCT in Type 2 diabetes mellitus (n=65). Empagliflozin vs. Placebo was evaluated on Change in VO2 peak (mL/min) (p=>0.050). Empagliflozin significantly reduced resting left ventricular end-diastolic volume by 9.51 mL compared to placebo in adults with type 2 diabetes, but did not improve peak oxygen consumption.

synapsesocial.com/papers/69cf5cd15a333a821460a533https://doi.org/10.1186/s40842-026-00281-9
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