Article Text

Download PDFPDF

Cardiovascular outcomes of type 2 diabetic patients treated with SGLT-2 inhibitors versus GLP-1 receptor agonists in real-life
  1. Enrico Longato1,
  2. Barbara Di Camillo1,
  3. Giovanni Sparacino1,
  4. Lorenzo Gubian2,
  5. Angelo Avogaro3,
  6. Gian Paolo Fadini3
  1. 1Department of Information Engineering, Università degli Studi di Padova, Padova, Veneto, Italy
  2. 2Azienda Zero, Regione Veneto, Padova, Veneto, Italy
  3. 3Department of Medicine, Università degli Studi di Padova, Padova, Veneto, Italy
  1. Correspondence to Professor Gian Paolo Fadini; gianpaolofadini{at}


Introduction Sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) protect type 2 diabetic (T2D) patients from cardiovascular events, but no trial has directly compared their cardiovascular effects. We aimed to address this gap using real-world data.

Research design and methods We performed a retrospective real-world study on a population of ~5 million inhabitants from North-East Italy. We identified T2D patients who received new prescription of SGLT2i or GLP-1RA from 2014 to 2018. SGLT2i and GLP-1RA initiators were matched 1:1 by propensity scores. The primary outcome was a composite of all-cause death, myocardial infarction, and stroke (three-point major adverse cardiovascular events (3P-MACE)). Secondary endpoints were each component of the primary endpoint, hospitalization for heart failure (HF), revascularization, hospitalization for cardiovascular causes, and adverse events.

Results From a population of 330 193 diabetic patients, we followed 8596 SGLT2i and GLP-1RA matched initiators for a median of 13 months. Patients in both groups were on average 63 years old, 63% men, and 18% had pre-existing cardiovascular disease. T2D patients treated with SGLT2i versus GLP-1RA, experienced a lower rate of 3P-MACE (HR 0.68; 95% CI 0.61 to 0.99; p=0.043), myocardial infarction (HR 0.72; 95% CI 0.53 to 0.98; p=0.035), hospitalization for HF (HR 0.59; 95% CI 0.35 to 0.99; p=0.048), and hospitalization for cardiovascular causes (HR 0.82; 95% CI 0.69 to 0.99; p=0.037). Adverse events were not significantly different between the two groups.

Conclusions In the absence of dedicated trials, this observational study suggests that SGLT2i may be more effective than GLP-1RA in improving cardiovascular outcomes of T2D.

Trial registration number NCT04184947.

  • glucagon-like peptide 1
  • observational study
  • cardiovascular system

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from


  • Contributors Study design: EL, BDC, GS, LG, AA, GPF. Data collection and analysis: EL, GPF. Manuscript writing: EL, AA, GPF. Manuscript revision: BDC, GS, LG. All authors approved the final version to be published.

  • Funding This work was supported by Institutional grants from the University of Padova. Part of this work was supported by MIUR (Italian Ministry for Education) under the initiative ‘Departments of Excellence’ (Law 232/2016). EL is supported by Arsenàl.IT, Veneto’s Research Centre for eHealth Innovation, through a PhD scholarship.

  • Competing interests AA received research grants, lecture or advisory board fees from Merck Sharp & Dome, AstraZeneca, Novartis, Boeringher-Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier, and Takeda. GPF received lecture fees or grant support from Abbott, AstraZeneca, Boehringer, Lilly, Merck-Sharp-Dome, Mundipharma, Novartis, Novo Nordisk, Sanofi, Servier.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. All the data used in this study were previously anonymized as per the Italian law concerning their usage for research and governance purposes. Study conduct was approved by the data owner board (Arsenàl.IT) and a formal ethics approval was deemed not necessary. Based on national regulations for retrospective studies on anonymized administrative claims, patients’ informed consent was not collected.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data will be available from the corresponding author at a reasonable request.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.