A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review
Cardiovascular and renal complications remain leading causes of morbidity and mortality among individuals with type 2 diabetes mellitus (T2DM). Since 2015, large-scale cardiovascular outcome trials (CVOTs) have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like pe...
- Autores:
-
Aristizábal-Colorado, David
Corredor-Rengifo, David
Sierra Castillo, Santiago
López-Corredor, carolina
Vernaza Trujillo, David Alexander
Weir-Restrepo, Danilo
Izquierdo-Condoy, Juan S.
Ortiz-Prado, Esteban
Rico-Fontalvo, Jorge
Gómez-Mesa, Juan Esteban
Abreu Lomba, Alin
Rivera Martínez, Wilfredo Antonio
- Tipo de recurso:
- Fecha de publicación:
- 2025
- Institución:
- Universidad Simón Bolívar
- Repositorio:
- Repositorio Digital USB
- Idioma:
- eng
- OAI Identifier:
- oai:bonga.unisimon.edu.co:20.500.12442/16821
- Acceso en línea:
- https://hdl.handle.net/20.500.12442/16821
https://doi.org/10.3389/fendo.2025.1605746
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1605746/full
- Palabra clave:
- Cardiovascular outcomes
SGLT2 inhibitors
GLP-1 agonists
Combination therapy
Heart failure
Renal outcomes
- Rights
- openAccess
- License
- Attribution-NonCommercial-NoDerivatives 4.0 International
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A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review |
| title |
A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review |
| spellingShingle |
A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review Cardiovascular outcomes SGLT2 inhibitors GLP-1 agonists Combination therapy Heart failure Renal outcomes |
| title_short |
A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review |
| title_full |
A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review |
| title_fullStr |
A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review |
| title_full_unstemmed |
A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review |
| title_sort |
A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review |
| dc.creator.fl_str_mv |
Aristizábal-Colorado, David Corredor-Rengifo, David Sierra Castillo, Santiago López-Corredor, carolina Vernaza Trujillo, David Alexander Weir-Restrepo, Danilo Izquierdo-Condoy, Juan S. Ortiz-Prado, Esteban Rico-Fontalvo, Jorge Gómez-Mesa, Juan Esteban Abreu Lomba, Alin Rivera Martínez, Wilfredo Antonio |
| dc.contributor.author.none.fl_str_mv |
Aristizábal-Colorado, David Corredor-Rengifo, David Sierra Castillo, Santiago López-Corredor, carolina Vernaza Trujillo, David Alexander Weir-Restrepo, Danilo Izquierdo-Condoy, Juan S. Ortiz-Prado, Esteban Rico-Fontalvo, Jorge Gómez-Mesa, Juan Esteban Abreu Lomba, Alin Rivera Martínez, Wilfredo Antonio |
| dc.subject.keywords.eng.fl_str_mv |
Cardiovascular outcomes SGLT2 inhibitors GLP-1 agonists Combination therapy Heart failure Renal outcomes |
| topic |
Cardiovascular outcomes SGLT2 inhibitors GLP-1 agonists Combination therapy Heart failure Renal outcomes |
| description |
Cardiovascular and renal complications remain leading causes of morbidity and mortality among individuals with type 2 diabetes mellitus (T2DM). Since 2015, large-scale cardiovascular outcome trials (CVOTs) have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduce the risk of major adverse cardiovascular events, cardiovascular mortality, and heart failure hospitalization in patients with T2DM and established cardiovascular disease or high-risk profiles. These findings—originating from landmark trials such as EMPA-REG OUTCOME, LEADER, and SUSTAIN-6—have led to substantial revisions in international guidelines from the European Society of Cardiology, American College of Cardiology, and American Heart Association, which now recommend the use of SGLT2i or GLP-1 RAs, often in conjunction with metformin. SGLT2i have shown robust effects in reducing heart failure hospitalization and slowing the progression of chronic kidney disease, while GLP-1 RAs have demonstrated superior efficacy in reducing atherothrombotic events, particularly non-fatal stroke. Additionally, emerging data supports the complementary use of both drug classes, revealing additive benefits on cardiovascular and renal outcomes without increased toxicity. This narrative review summarizes the mechanisms of action, clinical efficacy, safety profiles, and sex-specific outcomes associated with SGLT2i and GLP-1 RAs. It also highlights key evidence supporting their combined use and underscores their critical role in optimizing long-term outcomes in patients with T2DM and cardiovascular disease. |
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2025 |
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2025-07-10T20:30:54Z |
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2025-07-10T20:30:54Z |
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2025 |
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Artículo científico |
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Aristizábal-Colorado D, Corredor-Rengifo D, Sierra-Castillo S, López-Corredor C, Vernaza-Trujillo D-A, Weir-Restrepo D, Izquierdo-Condoy JS, Ortiz-Prado E, Rico-Fontalvo J, Gómez-Mesa J-E, Abreu-Lomba A and Rivera-Martínez W-A (2025) A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review. Front. Endocrinol. 16:1605746. doi: 10.3389/fendo.2025.1605746 |
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16642392 (Electrónico) |
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https://hdl.handle.net/20.500.12442/16821 |
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https://doi.org/10.3389/fendo.2025.1605746 |
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https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1605746/full |
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Aristizábal-Colorado D, Corredor-Rengifo D, Sierra-Castillo S, López-Corredor C, Vernaza-Trujillo D-A, Weir-Restrepo D, Izquierdo-Condoy JS, Ortiz-Prado E, Rico-Fontalvo J, Gómez-Mesa J-E, Abreu-Lomba A and Rivera-Martínez W-A (2025) A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review. Front. Endocrinol. 16:1605746. doi: 10.3389/fendo.2025.1605746 16642392 (Electrónico) |
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eng |
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Attribution-NonCommercial-NoDerivatives 4.0 International |
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pdf |
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Frontiers Media |
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Frontiers in Endocrinology Front. Endocrinol. |
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Vol. 16 No. Año 2025 |
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Aristizábal-Colorado, David68d7494f-ac81-4146-b8df-d989a92ef8ee-1Corredor-Rengifo, David7135d5c8-1431-4cd8-8765-2f2017466ae3600Sierra Castillo, Santiago259fc642-72b5-484c-baa6-7bcffce45eb1600López-Corredor, carolina6476b933-b99a-45fd-8ab8-3766d05a9514600Vernaza Trujillo, David Alexander1078ea17-8b3d-431f-a2f5-a5f3c6c7a5f4600Weir-Restrepo, Danilo7ae11fda-360b-4636-b603-873a550ea06b-1Izquierdo-Condoy, Juan S.5403a6bc-0d97-4a99-89f0-94379ef86151-1Ortiz-Prado, Esteban9283d6ad-d23f-459a-99d0-7379be2613a8600Rico-Fontalvo, Jorgeb6d7f264-85ba-46fd-884a-51398605f897600Gómez-Mesa, Juan Esteban0aef5655-c676-4a30-ba6a-9d9b27e476a3600Abreu Lomba, Alinde162463-6b5a-4bdc-a265-f84a5bba8fc0600Rivera Martínez, Wilfredo Antoniob567db58-c8e8-441e-a8da-efed2bee520b6002025-07-10T20:30:54Z2025-07-10T20:30:54Z2025Aristizábal-Colorado D, Corredor-Rengifo D, Sierra-Castillo S, López-Corredor C, Vernaza-Trujillo D-A, Weir-Restrepo D, Izquierdo-Condoy JS, Ortiz-Prado E, Rico-Fontalvo J, Gómez-Mesa J-E, Abreu-Lomba A and Rivera-Martínez W-A (2025) A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review. Front. Endocrinol. 16:1605746. doi: 10.3389/fendo.2025.160574616642392 (Electrónico)https://hdl.handle.net/20.500.12442/16821https://doi.org/10.3389/fendo.2025.1605746https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1605746/fullCardiovascular and renal complications remain leading causes of morbidity and mortality among individuals with type 2 diabetes mellitus (T2DM). Since 2015, large-scale cardiovascular outcome trials (CVOTs) have demonstrated that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduce the risk of major adverse cardiovascular events, cardiovascular mortality, and heart failure hospitalization in patients with T2DM and established cardiovascular disease or high-risk profiles. These findings—originating from landmark trials such as EMPA-REG OUTCOME, LEADER, and SUSTAIN-6—have led to substantial revisions in international guidelines from the European Society of Cardiology, American College of Cardiology, and American Heart Association, which now recommend the use of SGLT2i or GLP-1 RAs, often in conjunction with metformin. SGLT2i have shown robust effects in reducing heart failure hospitalization and slowing the progression of chronic kidney disease, while GLP-1 RAs have demonstrated superior efficacy in reducing atherothrombotic events, particularly non-fatal stroke. Additionally, emerging data supports the complementary use of both drug classes, revealing additive benefits on cardiovascular and renal outcomes without increased toxicity. This narrative review summarizes the mechanisms of action, clinical efficacy, safety profiles, and sex-specific outcomes associated with SGLT2i and GLP-1 RAs. It also highlights key evidence supporting their combined use and underscores their critical role in optimizing long-term outcomes in patients with T2DM and cardiovascular disease.pdfengFrontiers MediaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Frontiers in EndocrinologyFront. Endocrinol.Vol. 16 No. Año 2025A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive reviewinfo:eu-repo/semantics/articleArtículo científicohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_2df8fbb1Cardiovascular outcomesSGLT2 inhibitorsGLP-1 agonistsCombination therapyHeart failureRenal outcomesVos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. (2020) 396:1204–22. doi: 10.1016/S0140-6736(20)30925-9Coronado F, Melvin SC, Bell RA, and Zhao G. Global responses to prevent, manage, and control cardiovascular diseases. Prev Chronic Dis. (2022) 19:E84. doi: 10.5888/pcd19.220347Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. (2022) 183. doi: 10.1016/j.diabres.2021.109119Shah AD, Langenberg C, Rapsomaniki E, Denaxas S, Pujades-Rodriguez M, Gale CP, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people. Lancet Diabetes Endocrinol. (2015) 3:105–13. doi: 10.1016/S2213-8587(14)70219-0Dal Canto E, Ceriello A, Rydén L, Ferrini M, Hansen TB, Schnell O, et al. Diabetes as a cardiovascular risk factor: An overview of global trends of macro and micro vascular complications. Eur J Prev Cardiol. (2019) 26:25–32. doi: 10.1177/2047487319878371Kaze AD, Santhanam P, Musani SK, Ahima R, and Echouffo-Tcheugui JB. Metabolic dyslipidemia and cardiovascular outcomes in type 2 diabetes mellitus: findings from the look AHEAD study. J Am Heart Assoc. (2021) 10:e016947. doi: 10.1161/JAHA.120.016947Azam M, Sakinah LF, Kartasurya MI, Fibriana AI, Minuljo TT, and Aljunid SM. Prevalence and determinants of obesity among individuals with diabetes in Indonesia. F1000Research. (2022) 11:1063. doi: 10.12688/f1000research.125549.3Haile TG, Mariye T, Tadesse DB, Gebremeskel GG, Asefa GG, and Getachew T. Prevalence of hypertension among type 2 diabetes mellitus patients in Ethiopia: a systematic review and meta-analysis. Int Health. (2023) 15:235–41. doi: 10.1093/inthealth/ihac060Rodríguez-Gutiérrez R and Montori VM. Glycemic control for patients with type 2 diabetes mellitus: our evolving faith in the face of evidence. Circ Cardiovasc Qual Outcomes. (2016) 9:504–12. doi: 10.1161/CIRCOUTCOMES.116.002901UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. (1998) 352:837–53. doi: 10.1016/S0140-6736(98)07019-6The DCCT Research Group. Diabetes Control and Complications Trial (DCCT): results of feasibility study. The DCCT Research Group. Diabetes Care. (1987) 10:1–19. doi: 10.2337/diacare.10.1.1The DCCT Research Group. Diabetes Control and Complications Trial (DCCT): results of feasibility study. The DCCT Research Group. Diabetes Care. (1987) 10:1–19. doi: 10.2337/diacare.10.1.1Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal T, Hemmingsen C, et al. Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ. (2011) 343:d6898. doi: 10.1136/bmj.d6898Monami M, Candido R, Pintaudi B, Targher G, Mannucci E, and of the SID-AMD joint panel for Italian Guidelines on Treatment of Type 2 Diabetes. Improvement of glycemic control in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis NMCD. (2021) 31:2539–46. doi: 10.1016/j.numecd.2021.05.010Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC, Bigger JT, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. (2008) 358:2545–59. doi: 10.1056/NEJMoa0802743Crabtree T, Ogendo J-J, Vinogradova Y, Gordon J, and Idris I. Intensive glycemic control and macrovascular, microvascular, hypoglycemia complications and mortality in older (age ≥60years) or frail adults with type 2 diabetes: a systematic review and meta-analysis from randomized controlled trial and observation studies. Expert Rev Endocrinol Metab. (2022) 17:255–67. doi: 10.1080/17446651.2022.2079495Kilickap M, Kozluca V, Tan TS, and Akbulut Koyuncu IM. GLP-1 receptor agonists and SGLT-2 inhibitors in patients with versus without cardiovascular disease: A systematic review, meta-analysis, and trial sequential analysis. Angiology. (2024) 75:820–30. doi: 10.1177/00033197231183229Marilly E, Cottin J, Cabrera N, Cornu C, Boussageon R, Moulin P, et al. SGLT2 inhibitors in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials balancing their risks and benefits. Diabetologia. (2022) 65:2000–10. doi: 10.1007/s00125-022-05773-8Peronard R and Mayntz S. Comment on “SGLT2 inhibitors, and how they work beyond the glucosuric effect”. Am J Cardiovasc Drugs. (2024) 25:129–30. doi: 10.1007/s40256-024-00706-9Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. (2023) 389:1069–84. doi: 10.1056/NEJMoa2306963Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ, et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes: Developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC). Eur Heart J. (2023) 44:ehad192. doi: 10.1093/eurheartj/ehad192Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. (2022) 45:2753–86. doi: 10.2337/dci22-0034Rieg T and Vallon V. Development of SGLT1 and SGLT2 inhibitors. Diabetologia. (2018) 61:2079–86. doi: 10.1007/s00125-018-4654-7Hsia DS, Grove O, and Cefalu WT. An update on SGLT2 inhibitors for the treatment of diabetes mellitus. Curr Opin Endocrinol Diabetes Obes. (2017) 24:73–9. doi: 10.1097/MED.0000000000000311Aristizábal-Colorado D, Ocampo-Posada M, Rivera-Martínez WA, Corredor-Rengifo D, Rico-Fontalvo J, Gómez-Mesa JE, et al. SGLT2 inhibitors and how they work beyond the glucosuric effect. State of the art. Am J Cardiovasc Drugs. (2024) 24:707–18. doi: 10.1007/s40256-024-00673-1Fonseca-Correa JI and Correa-Rotter R. Sodium-glucose cotransporter 2 inhibitors mechanisms of action: A review. Front Med. (2021) 8:777861. doi: 10.3389/fmed.2021.777861Pabel S, Hamdani N, Luedde M, and Sossalla S. SGLT2 inhibitors and their mode of action in heart failure-has the mystery been unravelled? Curr Heart Fail Rep. (2021) 18:315–28. doi: 10.1007/s11897-021-00529-8Hiraizumi M, Akashi T, Murasaki K, Kishida H, Kumanomidou T, Torimoto N, et al. Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter. Nat Struct Mol Biol. (2024) 31:159–69. doi: 10.1038/s41594-023-01134-0Heerspink HJL, Perkins BA, Fitchett DH, Husain M, and Cherney DZI. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. (2016) 134:752–72. doi: 10.1161/CIRCULATIONAHA.116.021887Abdul-Ghani MA, DeFronzo RA, and Norton L. Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30-50% of filtered glucose load in humans. Diabetes. (2013) 62:3324–8. doi: 10.2337/db13-0604Lam-Chung CE. Comprehensive review of SGLT2 inhibitors’ efficacy through their diuretic mode of action in diabetic patients. Front Endocrinol. (2023) 14:1174692. doi: 10.3389/fendo.2023.1174692Li D, Wang T, Shen S, Fang Z, Dong Y, and Tang H. Urinary tract and genital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: A meta-analysis of randomized controlled trials. Diabetes Obes Metab. (2017) 19:348–55. doi: 10.1111/dom.12825Pittampalli S, Upadyayula S, Mekala HM, and Lippmann S. Risks vs benefits for SGLT2 inhibitor medications. Fed Pract. (2018) 35:45–8.Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. (2016) 101:157–66. doi: 10.1210/jc.2015-3167Neal B, Perkovic V, and Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 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