Effect of metformin and empagliflozin on myocardial function in insulin-resistant patients with heart failure: rationale and design of the METRIS-HF-DZHK18 Trial
Abstract
Impaired energy metabolism contributed to clinical severity, disease progression and to outcome in heart failure (HF). Insulin sensitivity (IS) is a key metabolic factor in the control of energy substrate utilisation and energy efficiency in cardiac and skeletal muscle. Impaired IS, or insulin resistance, is a common finding in HF and has been shown to predict morbidity and mortality in patients with heart failure with reduced and mildly reduced ejection fraction (HFrEF, HFmrEF). Despite its pathophysiologic relevance, IS has not been explored as a therapeutic target in HF. The objective of the METRIS-HF trial is to evaluate the effect of the insulin sensitizer metformin on top of standard care on myocardial contractility and functional capacity in insulin-resistant patients with HFrEF and HFmrEF in comparison to empagliflozin and placebo. METRIS-HF is an investigator initiated, multicentre, randomized, double-blind, placebo-controlled, double-dummy trial to enrol HF patients with reduced ejection fraction and insulin resistance into three parallel treatment arms in a 1:1:1 ratio to receive metformin 2x1000 daily), empagliflozin (1x10 mg/day), or double placebo, on top of standard heart failure therapy. The intervention lasts 24 weeks, followed by a 52-week follow-up period. The primary endpoint is the change in left ventricular global longitudinal strain (GLS) at 24 weeks. Key secondary endpoints include measurements of functional and symptomatic status such as 6-minute…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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