Hypokalemia and New-Onset Diabetes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

Q: What are the key findings of this study?

Lower time-updated serum potassium levels were associated with a higher rate of new-onset diabetes (aHR 1.19 per 0.5 mmol/L lower potassium) in patients with HFmrEF/HFpEF.

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) (n=3224). Intervention: Lower time-updated serum potassium (per 0.5 mmol/L decrease) vs. Higher serum potassium levels. Primary outcome: New-onset diabetes (aHR 1.19, 95% CI 1.04-1.36).

Q: What does this research mean for the field?

Hypokalemia is independently associated with an increased risk of new-onset diabetes in heart failure with mildly reduced or preserved ejection fraction, but changes in serum potassium only partially mediate finerenone's glycemic benefits. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

John W. Ostrominski; Henri Y. Lu; Brian Lee Claggett; Akshay Suvas Desai; Pardeep S. Jhund; Alasdair David Henderson; Carolyn S.P. Lam; Michele Senni; Sanjiv Jayendra Shah; Adriaan A. Voors; Faiez M. Zannad; Bertram Pitt; MEIKE DANIELA BRINKER; Andrea Viviana Scalise; Yoriko De Sanctis; Lucas H. Hofmeister; John J.V. McMurray; Scott David Solomon; Muthiah Vaduganathan

doi:10.2337/dc26-1305

Key result

Lower potassium is linked to ~19% higher new-onset diabetes risk per 0.5 mmol/L decrease in HFpEF/HFmrEF.

aHR 1.19
95% CI 1.04-1.36
n=3,224

Why the study?

Hypokalemia is common in HF and may contribute to glucose intolerance, but its influence on new-onset diabetes risk in HFmrEF/HFpEF remains uncertain.

Key Points

To evaluate the association between hypokalemia and new-onset diabetes in patients with heart failure with mildly reduced or preserved ejection fraction, and to determine whether finerenone's glycemic benefits are mediated by serum potassium levels.
Secondary analysis of the FINEARTS-HF randomized, placebo-controlled trial (NCT04435626) evaluating 3,224 participants without diabetes at baseline (mean age, 72±10 years; 47% female; mean serum potassium, 4.4±0.5 mmol/L) followed for a median of 2.7 years.
Assessed time-updated serum potassium and incident hypokalemia (<3.5 mmol/L and <4.0 mmol/L) using multivariable-adjusted Cox proportional hazards models.
Conducted causal mediation analyses to estimate the proportion of finerenone's effect on new-onset diabetes mediated by time-updated potassium and hypokalemia events.
Lower time-updated serum potassium was incrementally associated with higher rates of new-onset diabetes (aHR per 0.5 mmol/L lower, 1.19; 95% CI, 1.04-1.36), with no treatment modification (Pinteraction=0.29).
Rates of new-onset diabetes increased following incident hypokalemia <3.5 mmol/L (aHR, 2.07; 95% CI, 1.33-3.22) and serum potassium <4.0 mmol/L (aHR, 1.37; 95% CI, 1.05-1.80).
Finerenone's reduction of new-onset diabetes was estimated to be 20% mediated by time-updated serum potassium and 31% mediated by potassium levels combined with hypokalemia events.

Study Design

Type

Observational (n=3,224)

Multicenter

Yes

PICO

P

Population

3,224 adults with heart failure with mildly reduced or preserved ejection fraction, without baseline diabetes, followed for a median of 2.7 years.

E

Exposure / Comparator

Lower time-updated serum potassium (per 0.5 mmol/L decrease) vs Higher serum potassium levels

O

Primary Outcome

New-onset diabetes — aHR 1.19 (1.04-1.36)

Main Result

Hazard Ratio: 1.19 (95% CI 1.04–1.36)

Limitations

β-cell function and insulin resistance were not examined.
Use of glycemia measures other than HbA1c may have improved diabetes ascertainment.
Potential for residual confounding and reverse causation despite temporal association interrogation and multivariable adjustment.

Implication

Reveals higher new-onset diabetes risk linked to hypokalemia in heart failure with preserved ejection fraction, suggesting potassium maintenance partly explains finerenone benefits.

Abstract

International audience

Discussion

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Cite This Study

Ostrominski et al. (2026) conducted an observational in Heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) (n=3,224). Lower time-updated serum potassium (per 0.5 mmol/L decrease) vs. Higher serum potassium levels was evaluated on New-onset diabetes (aHR 1.19, 95% CI 1.04-1.36). Lower time-updated serum potassium levels were associated with a higher rate of new-onset diabetes (aHR 1.19 per 0.5 mmol/L lower potassium) in patients with HFmrEF/HFpEF.

synapsesocial.com/papers/6ad0fcd03afa093ea9ad0064 https://doi.org/10.2337/dc26-1305

Topics

HFrEF treatment

Heart failure

SGLT2 inhibitors in heart failure

Heart failure hospitalization

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Hypokalemia and New-Onset Diabetes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

Key Points

Study Design

PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Topics

Hypokalemia and New-Onset Diabetes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

Key Points

Study Design

PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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