---
title: "SGLT2 inhibitors and outcomes across cardio‑reno‑metabolic disease by BMI: a randomized trials met"
id: "pubmed-41948998"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-41948998"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/41948998/"
doi: "10.1093/ehjqcco/qcag061"
published_at: "2026-09-16T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# SGLT2 inhibitors and outcomes across cardio‑reno‑metabolic disease by BMI: a randomized trials met
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-41948998
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/41948998/)
- **DOI:** [10.1093/ehjqcco/qcag061](https://doi.org/10.1093%2Fehjqcco%2Fqcag061)
- **Published At:** 2026-09-16T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This meta-analysis pooled data from randomized controlled trials (RCTs) to evaluate whether **body mass index (BMI)** modifies the clinical benefits of **sodium–glucose cotransporter 2 inhibitors (SGLT2i)** across a spectrum of cardio‑reno‑metabolic (CRM) disease. - Eight RCTs with a combined 57,356 participants were included; the cohort had a mean BMI of 29.95 kg/m2. Trials compared SGLT2i with placebo in patients with heart failure (HF), chronic kidney disease (CKD), and/or type 2 diabetes (T2D). - Primary outcomes analyzed were the composite of **cardiovascular death or HF hospitalization**, its individual components, and **all‑cause mortality**, stratified by BMI using a 30 kg/m2 cutoff. - SGLT2i significantly reduced the risk of cardiovascular death or HF hospitalization in both BMI strata: RR 0.80 (95% CI 0.72–0.89) for BMI <30 kg/m2 and RR 0.80 (95% CI 0.75–0.85) for BMI ≥30 kg/m2, indicating no evidence of effect modification by BMI. - The observed composite benefit was driven primarily by reductions in **HF hospitalization** (RR 0.75 for BMI <30 kg/m2 and RR 0.74 for BMI ≥30 kg/m2). - Consistent reductions in **all‑cause death** were seen across BMI groups (RR 0.83 for BMI <30 kg/m2 and RR 0.89 for BMI ≥30 kg/m2). - Meta‑regression identified disease category (HF, CKD, T2D) and the individual SGLT2i molecule as sources of heterogeneity, but these did not alter the overall finding that BMI did not modify treatment effect. - Sensitivity, cumulative, and bootstrap analyses confirmed the robustness of the primary results as reported. - The authors conclude that across a broad CRM population, **SGLT2i** reduce the risk of cardiovascular death or HF hospitalization and all‑cause death irrespective of BMI. - Conflict of interest disclosures were reported for several authors and include honoraria, advisory roles, trial membership, and research grants from multiple pharmaceutical and medical device companies and the European Union; details are provided in the source.
## Clinical Analysis & Structured Key Points
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more resources ](https://pubmed.ncbi.nlm.nih.gov/41948998/#linkout) Title & authors Abstract Conflict of interest statement Comment in Similar articles Publication types MeSH terms Substances Related information LinkOut - more resources Meta-Analysis Eur Heart J Qual Care Clin Outcomes Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Eur+Heart+J+Qual+Care+Clin+Outcomes%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Eur+Heart+J+Qual+Care+Clin+Outcomes%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41948998/) . 2026 Sep 16;12(6):912-923. doi: 10.1093/ehjqcco/qcag061. # Sodium-glucose cotransporter 2 inhibitors across cardio-reno-metabolic disease and body mass index: a meta-analysis of randomized controlled trials [Dimitrios Farmakis](https://pubmed.ncbi.nlm.nih.gov/?term=Farmakis+D&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#full-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Konstantinos I Karampinos](https://pubmed.ncbi.nlm.nih.gov/?term=Karampinos+KI&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#full-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Chris J Kapelios](https://pubmed.ncbi.nlm.nih.gov/?term=Kapelios+CJ&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#full-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Sotiria Liori](https://pubmed.ncbi.nlm.nih.gov/?term=Liori+S&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#full-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Katerina Fountoulaki](https://pubmed.ncbi.nlm.nih.gov/?term=Fountoulaki+K&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#full-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Gerasimos Filippatos](https://pubmed.ncbi.nlm.nih.gov/?term=Filippatos+G&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#full-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece.") Affiliations Expand ### Affiliation * 1 From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece. * PMID: **41948998** * DOI: [ 10.1093/ehjqcco/qcag061 ](https://doi.org/10.1093/ehjqcco/qcag061) Item in Clipboard Meta-Analysis # Sodium-glucose cotransporter 2 inhibitors across cardio-reno-metabolic disease and body mass index: a meta-analysis of randomized controlled trials Dimitrios Farmakis et al. Eur Heart J Qual Care Clin Outcomes. 2026. Show details Display options Display options Format Abstract PubMed PMID Eur Heart J Qual Care Clin Outcomes Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Eur+Heart+J+Qual+Care+Clin+Outcomes%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Eur+Heart+J+Qual+Care+Clin+Outcomes%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41948998/) . 2026 Sep 16;12(6):912-923. doi: 10.1093/ehjqcco/qcag061. ### Authors [Dimitrios Farmakis](https://pubmed.ncbi.nlm.nih.gov/?term=Farmakis+D&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#short-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Konstantinos I Karampinos](https://pubmed.ncbi.nlm.nih.gov/?term=Karampinos+KI&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#short-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Chris J Kapelios](https://pubmed.ncbi.nlm.nih.gov/?term=Kapelios+CJ&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#short-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Sotiria Liori](https://pubmed.ncbi.nlm.nih.gov/?term=Liori+S&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#short-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Katerina Fountoulaki](https://pubmed.ncbi.nlm.nih.gov/?term=Fountoulaki+K&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#short-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece."), [Gerasimos Filippatos](https://pubmed.ncbi.nlm.nih.gov/?term=Filippatos+G&cauthor_id=41948998)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41948998/#short-view-affiliation-1 "From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece.") ### Affiliation * 1 From the Heart Failure Unit, Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens School of Medicine, 1 Rimini St, Haidari, 124 62 Athens, Greece. * PMID: **41948998** * DOI: [ 10.1093/ehjqcco/qcag061 ](https://doi.org/10.1093/ehjqcco/qcag061) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Aims:** Obesity is a central driver of cardio-reno-metabolic (CRM) disease and may influence pharmacological responsiveness. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes in heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes (T2D), but whether body mass index (BMI) modifies these benefits across a broad CRM spectrum remains uncertain. **Methods and results:** We performed a meta-analysis of randomized controlled trials (RCTs) comparing SGLT2i with placebo in patients with HF, CKD, and/or T2D and reported BMI-stratified outcomes using a cutoff of 30 kg/m2. Outcomes included the composite of cardiovascular death or HF hospitalization and its components, and all-cause death. Random-effects meta-analyses were performed using risk ratios (RR). Eight RCTs encompassing 57 356 patients were included (mean BMI 29.95 kg/m2). SGLT2i significantly reduced the risk of cardiovascular death or HF hospitalization in patients with BMI <30 kg/m2 (RR 0.80, 95% CI 0.72-0.89) and BMI ≥30 kg/m2 (RR 0.80, 95% CI 0.75-0.85), with no evidence of effect modification by BMI, an effect primarily driven by reductions in heart failure hospitalizations. Consistent benefits were observed for HF hospitalization (RR 0.75 for BMI <30 kg/m2 and 0.74 for BMI ≥30 kg/m2) and all-cause mortality (RR 0.83 for BMI <30 kg/m2 and 0.89 for BMI ≥30 kg/m2). Meta-regression identified disease category and SGLT2i molecule as sources of heterogeneity, without altering the absence of BMI interaction. Sensitivity, cumulative, and bootstrap analyses confirmed the robustness of the results. **Conclusion:** Across a broad CRM population, SGLT2i reduce cardiovascular death or HF hospitalization and all-cause death irrespective of BMI. **Keywords:** Body mass index; Chronic kidney disease; Diabetes; Heart failure; Obesity; Sodium–glucose cotransporter 2 inhibitors. © The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Conflict of interest: DF reports lecture or advisory board honoraria, trial committee membership or grants from Abbott, Astra-Zeneca, Bayer, Boehringer-Ingelheim, Eli-Lilly, Leo, Roche, Zoll, and research grants from the European Union, all outside the submitted work. CJK reports honoraria from Abbott, Astra-Zeneca, Bayer. KF reports honoraria from Astra-Zeneca and Boehringer-Ingelheim. GF reports lecture fees and/or advisory and/or trial committee membership by Bayer, Boehringer Ingelheim, Servier, Novartis, Impulse Dynamics, Vifor, Medtronic, Cardior, Novo Nordisc and Research Grants from the European Union. ## Comment in * [ Beyond body mass index: consistent benefits of sodium-glucose cotransporter 2 inhibitors and the limits of a convenient metric. ](https://pubmed.ncbi.nlm.nih.gov/42175717/) Chiriacò M, Castiglione V, Emdin M. Chiriacò M, et al. Eur Heart J Qual Care Clin Outcomes. 2026 Sep 16;12(6):924-926. doi: 10.1093/ehjqcco/qcag090. Eur Heart J Qual Care Clin Outcomes. 2026. PMID: 42175717 No abstract available. ## Similar articles * [ Sodium-Glucose Cotransporter-2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis. ](https://pubmed.ncbi.nlm.nih.gov/38583093/) Patel SM, Kang YM, Im K, Neuen BL, Anker SD, Bhatt DL, Butler J, Cherney DZI, Claggett BL, Fletcher RA, Herrington WG, Inzucchi SE, Jardine MJ, Mahaffey KW, McGuire DK, McMurray JJV, Neal B, Packer M, Perkovic V, Solomon SD, Staplin N, Vaduganathan M, Wanner C, Wheeler DC, Zannad F, Zhao Y, Heerspink HJL, Sabatine MS, Wiviott SD.Patel SM, et al.Circulation. 2024 Jun 4;149(23):1789-1801. doi: 10.1161/CIRCULATIONAHA.124.069568. Epub 2024 Apr 7.Circulation. 2024.PMID: 38583093Free PMC article. * [ Differential effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and renal outcomes according to renal function: a dose-response meta-analysis involving 10 randomized clinical trials and 71 553 individuals. ](https://pubmed.ncbi.nlm.nih.gov/37474112/) Lin DS, Yu AL, Lo HY, Lien CW, Lee JK, Chiang FT, Tu YK.Lin DS, et al.Eur J Endocrinol. 2023 Jul 20;189(1):S17-S25. doi: 10.1093/ejendo/lvad078.Eur J Endocrinol. 2023.PMID: 37474112 * [ Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes-Systematic review and meta-analysis of randomized placebo-controlled trials. ](https://pubmed.ncbi.nlm.nih.gov/33214130/) Salah HM, Al'Aref SJ, Khan MS, Al-Hawwas M, Vallurupalli S, Mehta JL, Mounsey JP, Greene SJ, McGuire DK, Lopes RD, Fudim M.Salah HM, et al.Am Heart J. 2021 Feb;232:10-22. doi: 10.1016/j.ahj.2020.10.064. Epub 2020 Oct 24.Am Heart J. 2021.PMID: 33214130 * [ The Effects of SGLT2 Inhibitors on Cardiovascular and Renal Outcomes in Diabetic Patients: A Systematic Review and Meta-Analysis. ](https://pubmed.ncbi.nlm.nih.gov/31743918/) Lo KB, Gul F, Ram P, Kluger AY, Tecson KM, McCullough PA, Rangaswami J.Lo KB, et al.Cardiorenal Med. 2020;10(1):1-10. doi: 10.1159/000503919. Epub 2019 Nov 19.Cardiorenal Med. 2020.PMID: 31743918 * [ Prevention of heart failure events with sodium-glucose co-transporter 2 inhibitors across a spectrum of cardio-renal-metabolic risk. ](https://pubmed.ncbi.nlm.nih.gov/33609071/) Bhatia K, Jain V, Gupta K, Bansal A, Fox A, Qamar A, Damman K, Vaduganathan M.Bhatia K, et al.Eur J Heart Fail. 2021 Jun;23(6):1002-1008. doi: 10.1002/ejhf.2135. Epub 2021 Mar 8.Eur J Heart Fail. 2021.PMID: 33609071 [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=41948998) ## Publication types * Meta-Analysis Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Meta-Analysis%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Meta-Analysis) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41948998/) ## MeSH terms * Body Mass Index* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Body+Mass+Index%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Body+Mass+Index) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41948998/) * Diabetes Mellitus, Type 2* / complications Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Diabetes+Mellitus%2C+Type+2%2Fcomplications%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Diabetes+Mellitu
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