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DOI: 10.1055/a-2606-7020
Adipositas und Herz: neue Medikamente und neue Strategien für Kardiologen
Obesity and Heart: New Drugs and New Strategies for Cardiologists
Zusammenfassung
Die Adipositastherapie erlebt durch Inkretin-basierte Medikamente (GLP-1- und GIP/GLP-1-Rezeptoragonisten) und SGLT-2-Inhibitoren (SGLT2i) eine Revolution mit direkten Implikationen für die Kardiologie. Substanzen wie Semaglutid und Tirzepatid ermöglichen eine bislang nicht erreichte Gewichtsreduktion, reduzieren nachweislich kardiovaskuläre Ereignisse (MACE) und verbessern Endpunkte bei Herzinsuffizienz mit erhaltener Ejektionsfraktion (HFpEF), auch bei Menschen ohne Diabetes. SGLT2i sind etabliert zur Reduktion von Herzinsuffizienzhospitalisierungen und Nierenendpunkten über das gesamte Herzinsuffizienzspektrum und bei chronischer Nierenerkrankung. Die Kombination von GLP-1-Rezeptoragonisten und SGLT2i zeigt additive Vorteile und wird leitliniengerecht bei Typ-2-Diabetes mit hohem Risiko empfohlen. Für Kardiologen bedeutet dies einen Paradigmenwechsel: Adipositas wird zu einem aktiv behandelbaren kardiovaskulären Risikofaktor. Die Integration dieser Therapien erfordert Wissen über Indikationen, Kontraindikationen, Nebenwirkungsmanagement und Langzeitstrategien. Zukünftige Multiagonisten versprechen noch stärkere Effekte, ihre kardiovaskuläre Sicherheit muss aber belegt werden.
Abstract
Obesity therapy is undergoing a revolution driven by incretin-based medications (GLP-1- andGIP/GLP-1 receptor agonists) and SGLT2 inhibitors (SGLT2i), with direct implications for cardiology. Agents such as semaglutide and tirzepatide enable unprecedented weight loss and have been shown to reduce major adverse cardiovascular events (MACE) and improve outcomes in heart failure with preserved ejection fraction (HFpEF), even in non-diabetic patients. SGLT2i are well established for reducing heart failure hospitalizations and renal endpoints across the entire heart failure spectrum and in chronic kidney disease. The combination of GLP-1 receptor agonists and SGLT2i shows additive benefits and is guideline-recommended for patients with type 2 diabetes at high cardiovascular risk. For cardiologists, this marks a paradigm shift: obesity is becoming an actively treatable cardiovascular risk factor. Integrating these therapies requires knowledge of indications, contraindications, side effect management, and long-term strategies. Future multi-agonists promise even greater effects, though their cardiovascular safety still needs to be demonstrated.
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Inkretin-Mimetika (Semaglutid, Tirzepatid) ermöglichen nicht nur signifikante Gewichtsreduktion, sondern reduzieren auch kardiovaskuläre Ereignisse bei Adipositas: Major Adverse Cardiovascular Events (MACE) bei koronarer Herzerkrankung (KHK), Herzinsuffizienz-Events (HF-Events) bei Herzinsuffizienz mit erhaltener Ejektionsfraktion (HFpEF).
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Die Kombination von GLP-1-Rezeptoragonisten und SGLT-2-Inhibitoren zeigt additive kardiometabolische Vorteile und wird zunehmend leitliniengerecht bei Patienten mit Typ-2-Diabetes und hohem kardiorenalem Risiko empfohlen.
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Die Pipeline an zukünftigen Adipositasmedikamenten (z. B. Retatrutid, CagriSema) verspricht noch potentere Wirkstoffe mit potenziell verbesserten kardiometabolischen Profilen; entscheidende kardiovaskuläre Endpunktstudien sind jedoch abzuwarten.
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Die Behandlung der Adipositas selbst rückt durch diese neuen Optionen in den Fokus des kardiovaskulären Risikomanagements, erfordert aber ein Management von Nebenwirkungen und eine Langzeitperspektive.
Schlüsselwörter
Adipositas - GLP-1-Rezeptoragonisten - SGLT2-Inhibitoren - Herzinsuffizienz - kardiovaskuläre PräventionKeywords
obesity - GLP-1 receptor agonists - SGLT2 inhibitors - cardiovascular prevention - heart failurePublication History
Article published online:
06 August 2025
© 2025. Thieme. All rights reserved.
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Literatur
- 1 Bogers RP, Bemelmans WJ, Hoogenveen RT. et al. Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med 2007; 167: 1720-1728
- 2 Borlaug BA, Jensen MD, Kitzman DW. et al. Obesity and heart failure with preserved ejection fraction: new insights and pathophysiological targets. Cardiovasc Res 2023; 118: 3434-3450
- 3 Koskinas KC, Van Craenenbroeck EM, Antoniades C. et al. Obesity and cardiovascular disease: an ESC clinical consensus statement. Eur Heart J 2024; 45: 4063-4098
- 4 Samms RJ, Kusminski CM. A Mechanistic Rationale for Incretin-Based Therapeutics in the Management of Obesity. Annu Rev Physiol 2025; 87: 279-299
- 5 Marso SP, Daniels GH, Brown-Frandsen K. et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-322
- 6 Pi-Sunyer X, Astrup A, Fujioka K. et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 2015; 373: 11-22
- 7 Marso SP, Bain SC, Consoli A. et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2016; 375: 1834-1844
- 8 Wilding JPH, Batterham RL, Calanna S. et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021; 384: 989-1002
- 9 Lincoff AM, Brown-Frandsen K, Colhoun HM. et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med 2023; 389: 2221-2232
- 10 Jastreboff AM, Aronne LJ, Ahmad NN. et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022; 387: 205-216
- 11 Kosiborod MN, Abildstrøm SZ, Borlaug BA. et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med 2023; 389: 1069-1084
- 12 Packer M, Zile MR, Kramer CM. et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med 2025; 392: 427-437
- 13 Osei SP, Akomaning E, Florut TF. et al. Gastrointestinal Safety Assessment of GLP-1 Receptor Agonists in the US: A Real-World Adverse Events Analysis from the FAERS Database. Diagnostics (Basel) 2024; 14: 2829
- 14 Liu L. A real-world data analysis of tirzepatide in the FDA adverse event reporting system (FAERS) database. Front Pharmacol 2024; 15: 1397029
- 15 Xie Y, Choi T, Al-Aly Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med 2025; 31: 951-962
- 16 Bezin J, Gouverneur A, Pénichon M. et al. GLP-1 Receptor Agonists and the Risk of Thyroid Cancer. Diabetes Care 2022; 46: 384-390
- 17 Pasternak B, Wintzell V, Hviid A. et al. Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ 2024; 385: e078225
- 18 Baxter SM, Lund LC, Andersen JH. et al. Glucagon-Like Peptide 1 Receptor Agonists and Risk of Thyroid Cancer: An International Multisite Cohort Study. Thyroid 2025; 35: 69-78
- 19 Tracey W, Lingfeng Y, Richard DC. et al. Real-world weight change, adherence, and discontinuation among patients with type 2 diabetes initiating glucagon-like peptide-1 receptor agonists in the UK. BMJ Open Diabetes Res Care 2022; 10: e002517
- 20 Zinman B, Wanner C, Lachin JM. et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373: 2117-2128
- 21 Neal B, Perkovic V, Mahaffey KW. et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377: 644-657
- 22 Wiviott SD, Raz I, Bonaca MP. et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019; 380: 347-357
- 23 McMurray JJV, Solomon SD, Inzucchi SE. et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019; 381: 1995-2008
- 24 Packer M, Anker SD, Butler J. et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med 2020; 383: 1413-1424
- 25 Anker SD, Butler J, Filippatos G. et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med 2021; 385: 1451-1461
- 26 Solomon SD, McMurray JJV, Claggett B. et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med 2022; 387: 1089-1098
- 27 Heerspink HJL, Stefánsson BV, Correa-Rotter R. et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2020; 383: 1436-1446
- 28 Herrington WG, Staplin N, Wanner C. et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2023; 388: 117-127
- 29 Fonseca-Correa JI, Correa-Rotter R. Sodium-Glucose Cotransporter 2 Inhibitors Mechanisms of Action: A Review. Front Med (Lausanne) 2021; 8: 777861
- 30 Lajara R. Combination therapy with SGLT-2 inhibitors and GLP-1 receptor agonists as complementary agents that address multi-organ defects in type 2 diabetes. Postgrad Med 2019; 131: 555-565
- 31 DeFronzo RA. Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes Obes Metab 2017; 19: 1353-1362
- 32 Neves JS, Borges-Canha M, Vasques-Nóvoa F. et al. GLP-1 Receptor Agonist Therapy With and Without SGLT2 Inhibitors in Patients With Type 2 Diabetes. J Am Coll Cardiol 2023; 82: 517-525
- 33 Apperloo EM, Neuen BL, Fletcher RA. et al. 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. Lancet Diabetes Endocrinol 2024; 12: 545-557
- 34 Simms-Williams N, Treves N, Yin H. et al. Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study. BMJ 2024; 385: e078242
- 35 Yepes-Cortés CA, Cardenas-Moreno IC, Daza-Arnedo R. et al. Combining GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes Mellitus: A Scoping Review and Expert Insights for Clinical Practice Utilizing the Nominal Group Technique. Diabetes Ther 2025; 16: 813-849
- 36 Wharton S, Blevins T, Connery L. et al. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. N Engl J Med 2023; 389: 877-888
- 37 Melson E, Ashraf U, Papamargaritis D. et al. What is the pipeline for future medications for obesity?. Int J Obes (Lond) 2025; 49: 433-451
- 38 Jastreboff AM, Kaplan LM, Frías JP. et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity – A Phase 2 Trial. N Engl J Med 2023; 389: 514-526