{
  "abstract": "Background and Importance Cardio-Renal-Metabolic syndrome results from interactions between cardiovascular, metabolic, and renal risk factors, causing multi-organ dysfunction, increased morbidity, and premature mortality. Sodium–glucose cotransporter-2 inhibitors (SGLT2i), Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA), and Mineralocorticoid Receptor Antagonists (MRA) exert pleiotropic effects and improve cardiovascular and renal outcomes beyond glycaemic control.Aim and Objectives To compare the risk–benefit profile of currently available pharmacological therapies, with a specific focus on their clinical efficacy and safety.Material and Methods A systematic review (SR) was conducted by searching PubMed, according to the PRISMA guidelines, for studies published between 8 August 2015 and 8 August 2025. Search terms combined ‘SGLT2 inhibitors’, diabetes, ‘chronic kidney disease’, cardiovascular disease’, and ‘CRM syndrome’. Eligible outcomes included major adverse cardiovascular events (MACE), renal outcomes, and safety.Results The search retrieved 1.335 articles; 778 were screened after applying filters for the last 10 years and selecting only systematic reviews, reviews, meta-analyses, and RCT. Thirty-six full texts were assessed, resulting in 12 RCT included studies and eight additional articles identified through reference mining. Dapagliflozin reduced the risk of cardiovascular (CV) death or hospitalisation for heart failure (HF) by 29% [HR 0.71; 95% CI 0.55–0.92] and slowed kidney disease progression by 24% [HR 0.76; 95% CI 0.67–0.87]. Canagliflozin reduced the composite renal outcome [HR 0.66; 95% CI 0.53–0.81], HF hospitalisations [HR 0.61; 95% CI 0.47–0.80], and major adverse cardiovascular events (MACE) [HR 0.80; 95% CI 0.67–0.95]. Empagliflozin lowered MACE [HR 0.86; 95% CI 0.74–0.99], all-cause mortality (−32%), and CKD progression [HR 0.72; 95% CI 0.64–0.82], while ertugliflozin demonstrated non-inferiority for MACE and reduced HF hospitalisations by 30%. Consistently, semaglutide (GLP-1RA) and finerenone (MRA) also showed favourable effects: semaglutide reduced MACE by up to 26% [HR 0.74; 95% CI 0.51–1.08], whereas finerenone decreased HF hospitalisations by 17% [HR 0.83; 95% CI 0.75–0.92] and the composite renal outcome by 20% [HR 0.80; 95% CI 0.72–0.90].Conclusion and Relevance Our analysis confirms the role of SGLT2 inhibitors and GLP-1 receptor agonists in the management of CRM syndrome, demonstrating cardiovascular and renal benefits, improved survival and quality of life, and a favourable safety profile.Conflict of Interest No conflict of interest",
  "authors": [
    {
      "affiliations": [
        "Azienda Unica Sanitaria Locale Di Bologna, Dipartimento Farmaceutico Interaziendale Azienda Usl Di Bologna – Irccs Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy"
      ],
      "name": "A Colicchio"
    },
    {
      "affiliations": [
        "Azienda Sanitaria Locale N.4 Di Teramo, U.O.C -Servizio Farmaceutico Territoriale – Crfv Abruzzo, Teramo, Italy"
      ],
      "name": "I Di Cesare"
    }
  ],
  "title": "6ER-018 Therapeutic strategies in cardio-renal-metabolic syndrome: a systematic review",
  "uid": "d8bdcfd0-6867-52d0-9b0a-26db40d82f33"
}