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Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials.
Apperloo, Ellen M; Neuen, Brendon L; Fletcher, Robert A; Jongs, Niels; Anker, Stefan D; Bhatt, Deepak L; Butler, Javed; Cherney, David Z I; Herrington, William G; Inzucchi, Silvio E; Jardine, Meg J; Liu, Chih-Chin; Mahaffey, Kenneth W; McGuire, Darren K; McMurray, John J V; Neal, Bruce; Packer, Milton; Perkovic, Vlado; Sabatine, Marc S; Solomon, Scott D; Staplin, Natalie; Szarek, Michael; Vaduganathan, Muthiah; Wanner, Christoph; Wheeler, David C; Wiviott, Stephen D; Zannad, Faiez; Heerspink, Hiddo J L.
Afiliação
  • Apperloo EM; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
  • Neuen BL; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Department of Renal Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.
  • Fletcher RA; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
  • Jongs N; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
  • Anker SD; Department of Cardiology and Berlin Institute of Health Center for Regenerative Therapies, German Center for Cardiovascular Research Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.
  • Bhatt DL; Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Butler J; Baylor Scott and White Research Institute, Dallas, TX, USA; Department of Medicine, University of Mississippi School of Medicine, Jackson, MS, USA.
  • Cherney DZI; Department of Medicine, Division of Nephrology, Toronto General Hospital, ON, Canada.
  • Herrington WG; Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Inzucchi SE; Section of Endocrinology, Yale School of Medicine, New Haven, CT, USA.
  • Jardine MJ; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia; Department of Renal Medicine, Concord Repatriation General Hospital, Sydney, NSW, Australia.
  • Liu CC; Merck, Rahway, NJ, USA.
  • Mahaffey KW; Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • McGuire DK; University of Texas Southwestern Medical Center and Parkland Health, Dallas, TX, USA.
  • McMurray JJV; British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
  • Neal B; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Packer M; Baylor University Medical Center, Dallas TX, USA; Imperial College, London, UK.
  • Perkovic V; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
  • Sabatine MS; TIMI Study Group, Boston, MA, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Solomon SD; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Staplin N; Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Szarek M; Division of Cardiology, University of Colorado School of Medicine, Aurora, CO, USA; Colorado Prevention Center Clinical Research, Aurora, CO, USA; State University of New York, Downstate Health Sciences University, Brooklyn, NY, USA.
  • Vaduganathan M; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Wanner C; Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Centre, University Hospital, Würzburg, Germany.
  • Wheeler DC; Department of Renal Medicine, University College London, London, UK.
  • Wiviott SD; TIMI Study Group, Boston, MA, USA; Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Zannad F; Université de Lorraine, Inserm, Center d'Investigations Cliniques, Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.
  • Heerspink HJL; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia. Electronic address: h.j.lambers.heerspink@umcg.nl.
Lancet Diabetes Endocrinol ; 12(8): 545-557, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38991584
ABSTRACT

BACKGROUND:

SGLT2 inhibitors and GLP-1 receptor agonists both improve cardiovascular and kidney outcomes in patients with type 2 diabetes. We sought to evaluate whether the benefits of SGLT2 inhibitors are consistent in patients receiving and not receiving GLP-1 receptor agonists.

METHODS:

We conducted a collaborative meta-analysis of trials included in the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium, restricted to participants with diabetes. Treatment effects from individual trials were obtained from Cox regression models and pooled using inverse variance weighted meta-analysis. The two main cardiovascular outcomes assessed included major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), and hospitalisation for heart failure or cardiovascular death. The main kidney outcomes assessed were chronic kidney disease progression (≥40% decline in estimated glomerular filtration rate [eGFR], kidney failure [eGFR <15 mL/min/1·73 m2, chronic dialysis, or kidney transplantation], or death due to kidney failure), and the rate of change in eGFR over time. Safety outcomes were also assessed.

FINDINGS:

Across 12 randomised, double-blind, placebo-controlled trials, 3065 (4·2%) of 73 238 participants with diabetes were using GLP-1 receptor agonists at baseline. SGLT2 inhibitors reduced the risk of major adverse cardiovascular events in participants both receiving and not receiving GLP-1 receptor agonists (hazard ratio [HR] 0·81, 95% CI 0·63-1·03 vs 0·90, 0·86-0·94; p-heterogeneity=0·31). Effects on hospitalisation for heart failure or cardiovascular death (0·76, 0·57-1·01 vs 0·78, 0·74-0·82; p-heterogeneity=0·90) and chronic kidney disease progression (0·65, 0·46-0·94 vs 0·67, 0·62-0·72; p-heterogeneity=0·81) were also consistent regardless of GLP-1 receptor agonist use, as was the effect on the chronic rate of change in eGFR over time (heterogeneity=0·92). Fewer serious adverse events occurred with SGLT2 inhibitors compared with placebo, irrespective of GLP-1 receptor agonist use (relative risk 0·87, 95% CI 0·79-0·96 vs 0·91, 0·89-0·93; p-heterogeneity=0·41).

INTERPRETATION:

The effects of SGLT2 inhibitors on cardiovascular and kidney outcomes are consistent regardless of the background use of GLP-1 receptor agonists. These findings suggest independent effects of these evidence-based therapies and support clinical practice guidelines recommending the use of these agents in combination to improve cardiovascular and kidney metabolic outcomes.

FUNDING:

National Health and Medical Research Council of Australia and the Ramaciotti Foundation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ensaios Clínicos Controlados Aleatórios como Assunto / Diabetes Mellitus Tipo 2 / Receptor do Peptídeo Semelhante ao Glucagon 1 / Inibidores do Transportador 2 de Sódio-Glicose Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ensaios Clínicos Controlados Aleatórios como Assunto / Diabetes Mellitus Tipo 2 / Receptor do Peptídeo Semelhante ao Glucagon 1 / Inibidores do Transportador 2 de Sódio-Glicose Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article