Minerva Cardiology and Angiology 2022 Feb 23

DOI: 10.23736/S2724-5683.22.05900-2

Copyright © 2022 EDIZIONI MINERVA MEDICA

lingua: Inglese

Comparing benefits from sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in randomized clinical trials: a network meta-analysis

Pierre SABOURET ¹ ✉, Pier Paolo BOCCHINO ², Filippo ANGELINI ², Fabrizio D’ASCENZO ², Giuseppe GALATI ³, Marinos FYSEKIDIS ⁴, Gaetano M. DE FERRARI ², David L. FISCHMAN ⁵, Deepak L. BHATT ⁶, Giuseppe BIONDI-ZOCCAI ^{7, 8}

¹ Cardiology Department, Heart Institute and Action Group, Pitié-Salpétrière, Sorbonne University Paris, Paris, France; ² Division of Cardiology, Department of Medical Science, University of Turin, Città della Salute e Della Scienza, Turin, Italy; ³ Heart Failure Unit, Division of Cardiology, Cardiothoracic and Vascular Department, San Raffaele Hospital and Scientific Institute (IRCCS), Milan, Italy; ⁴ Department of Endocrinology, Avicenne Hospital, AP-HP, Bobigny, France; ⁵ Cardiology Department, Thomas Jefferson University, Philadelphia, PA, USA; ⁶ Brigham and Women’s Hospital, Heart and Vascular Center and Harvard Medical School, Boston, MA, USA; ⁷ Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; ⁸ Mediterranea Cardiocentro, Napoli, Italy

INTRODUCTION: Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) were individually proven to reduce major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients, but the relative magnitude of benefits from these two drug classes is debated. We aimed to review current available data on GLP1-RA and SGLT2i in T2DM patients and compare their efficacy and safety in this population.
EVIDENCE ACQUISITION: We systematically searched MEDLINE/PubMed, the Cochrane Library, Google Scholar, Embase, www.tctmd.com, www.clinicaltrials.gov, www.clinicaltrialresults.org, from inception to September 17, 2020 for randomized controlled trials (RCTs) comparing the effects of GLP1-RA vs SGLT2i vs optimal medical therapy (OMT) in adult T2DM patients. Three authors independently screened references and extracted data using a predefined data collection form. Outcomes were analyzed using an indirect comparison meta-analysis of aggregate study-level data. The primary combined efficacy outcome comprised cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke. Secondary efficacy outcomes included all-cause mortality, cardiovascular mortality, non-fatal MI, non-fatal stroke, heart failure hospitalizations (HFH), and worsening renal function (WRF).
EVIDENCE SYNTHESIS: 11 RCTs enrolling a total of 98572 patients were included; 56004 (57%) patients were derived from GLP1-RA RCTs and 42568 (43%) from SGLT2i RCTs. At a median follow-up of 3.0±1.3 years, compared with OMT, both GLP1-RA and SGLT2i similarly reduced the rate of the composite primary outcome (risk ratio [RR] 0.88; 95% confidence interval [95%CI] 0.83-0.93 and RR 0.88, 95%CI 0.82-0.95, respectively) with no difference between the drug classes (RR 1.00, 95%CI 0.92-1.10). Both classes similarly reduced MI rate, cardiovascular and all-cause mortality compared with OMT; stroke reduction was only observed with GLP1-RA with no difference in the indirect comparison with SGLT2i; conversely, only SGLT2i were effective in preventing HFH. Both GLP1-RA and SGLT2i were protective against WRF, with a major efficacy of SGLT2i in the indirect comparison.
CONCLUSIONS: This meta-analysis report that GLP1-RA and SGLT2i reduced with a similar efficacy not only MACE as MI, but also cardiovascular mortality and all-cause mortality at a median 3 years follow-up. SGLT2i were more protective in HFH and WRF than GLP1RA. These new data highlight the efficacy of SGLT2i not only in HF and chronic kidney disease (CKD) but also in ischemic heart diseases (IHD), with a homogeneity among the class, whereas the results observed with GLP1-RA are heterogenous. These findings will help clinical’s decisions to optimize therapeutic strategies for diabetic patients.

KEY WORDS: Diabetes; Meta-analysis; GLP1RA; SGLT2i; Residual risk