Effect of SGLT2 inhibitors on heart failure outcomes and cardiovascular death across the cardiometabolic disease spectrum: a systematic review and meta-analysis

Muhammad Shariq Usman; Deepak L Bhatt; Ishaque Hameed; Stefan D Anker; Alice Y Y Cheng; Adrian F Hernandez; William Schuyler Jones; Muhammad Shahzeb Khan; Mark C Petrie; Jacob A Udell; Tim Friede; Javed Butler

doi:10.1016/S2213-8587(24)00102-5

Effect of SGLT2 inhibitors on heart failure outcomes and cardiovascular death across the cardiometabolic disease spectrum: a systematic review and meta-analysis

Lancet Diabetes Endocrinol. 2024 May 17:S2213-8587(24)00102-5. doi: 10.1016/S2213-8587(24)00102-5. Online ahead of print.

Authors

Affiliations

¹ Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
² Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ Department of Medicine, Medstar Health, Baltimore, MD, USA.
⁴ Department of Internal Medicine and Cardiology, Campus Virchow-Klinikum, German Heart Center Charité, Charité-University Medicine Berlin, Corporate Member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany; BIH Center for Regenerative Therapies (BCRT), Charité-University Medicine Berlin, Corporate Member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany.
⁵ Department of Medicine, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada.
⁶ Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA; Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.
⁷ Division of Cardiology, Duke University School of Medicine, Duke University Medical Center, Durham, NC, USA.
⁸ School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
⁹ Women's College Hospital and Peter Munk Cardiac Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Göttingen, Göttingen, Germany.
¹¹ Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, TX, USA; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA. Electronic address: javed.butler@bswhealth.org.

PMID: 38768620
DOI: 10.1016/S2213-8587(24)00102-5

Abstract

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been studied in patients with heart failure, type 2 diabetes, chronic kidney disease, atherosclerotic cardiovascular disease, and acute myocardial infarction. Individual trials were powered to study composite outcomes in one disease state. We aimed to evaluate the treatment effect of SGLT2 inhibitors on specific clinical endpoints across multiple demographic and disease subgroups.

Methods: In this systematic review and meta-analysis, we queried online databases (PubMed, Cochrane CENTRAL, and SCOPUS) up to Feb 10, 2024, for primary and secondary analyses of large trials (n>1000) of SGLT2 inhibitors in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease (including acute myocardial infarction). Outcomes studied included composite of first hospitalisation for heart failure or cardiovascular death, first hospitalisation for heart failure, cardiovascular death, total (first and recurrent) hospitalisation for heart failure, and all-cause mortality. Effect sizes were pooled using random-effects models. This study is registered with PROSPERO, CRD42024513836.

Findings: We included 15 trials (N=100 952). Compared with placebo, SGLT2 inhibitors reduced the risk of first hospitalisation for heart failure by 29% in patients with heart failure (hazard ratio [HR] 0·71 [95% CI 0·67-0·77]), 28% in patients with type 2 diabetes (0·72 [0·67-0·77]), 32% in patients with chronic kidney disease (0·68 [0·61-0·77]), and 28% in patients with atherosclerotic cardiovascular disease (0·72 [0·66-0·79]). SGLT2 inhibitors reduced cardiovascular death by 14% in patients with heart failure (HR 0·86 [95% CI 0·79-0·93]), 15% in patients with type 2 diabetes (0·85 [0·79-0·91]), 11% in patients with chronic kidney disease (0·89 [0·82-0·96]), and 13% in patients with atherosclerotic cardiovascular disease (0·87 [0·78-0·97]). The benefit of SGLT2 inhibitors on both first hospitalisation for heart failure and cardiovascular death was consistent across the majority of the 51 subgroups studied. Notable exceptions included acute myocardial infarction (22% reduction in first hospitalisation for heart failure; no effect on cardiovascular death) and heart failure with preserved ejection fraction (26% reduction in first hospitalisation for heart failure; no effect on cardiovascular death).

Interpretation: SGLT2 inhibitors reduced heart failure events and cardiovascular death in patients with heart failure, type 2 diabetes, chronic kidney disease, and atherosclerotic cardiovascular disease. These effects were consistent across a wide range of subgroups within these populations. This supports the eligibility of a large population with cardiorenal-metabolic diseases for treatment with SGLT2 inhibitors.

Funding: None.