Diabetes medications with cardiovascular protection: the likelihood of benefit from combination therapy increases further following new evidence during 2020
Keywords:Type 2 diabetes, cardiovascular outcome studies, pioglitazone, SGLT2 inhibitors, GLP-1 receptor agonist, heart failure, stroke
Ryder REJ, DeFronzo RA. Diabetes medications with cardiovascular protection in the wake of EMPA-REG OUTCOME™: the optimal combination may be metformin, pioglitazone and empagliflozin. Br J Diabetes Vasc Dis 2015; 15:151–4. http://dx.doi.org/10.15277/bjdvd.2015.045
Ryder REJ, DeFronzo RA. Diabetes medications with cardiovascular protection – what now after LEADER®? Could metformin, pioglitazone, empagliflozin and liraglutide complement each other to save lives? Br J Diabetes 2016;16:103–6. http://dx.doi.org/10.15277/bjd.2016.096
Ryder REJ, DeFronzo RA. What now on the CANVAS of diabetes medications with cardiovascular protection? Could metformin, pioglitazone, SGLT2 inhibitors and liraglutide complement each other to save lives? Br J Diabetes 2017;17:89–92. http://dx.doi.org/10.15277/bjd.2017.036
Ryder REJ, DeFronzo RA. Diabetes medications with cardiovascular protection in the wake of EXSCEL – is there a class effect for long-acting GLP-1 receptor agonists? Br J Diabetes 2017;17:131–3. https://doi.org/10.15277/bjd.2017.147
Ryder REJ, DeFronzo RA. Diabetes medications with cardiovascular protection after HARMONY Outcomes and DECLARE-TIMI 58: could metformin, pioglitazone, SGLT2 inhibitors and long-acting GLP-1 receptor agonists complement each other to save lives by different mechanisms? Br J Diabetes 2019;19:1–5. https://doi.org/10.15277/bjd.2019.207
Ryder REJ, DeFronzo RA. Diabetes medications with cardiovascular protection as we enter a new decade: can SGLT2 inhibitors, long-acting GLP-1 receptor agonists, pioglitazone and metformin complement each other to save lives? Br J Diabetes 2020;20:5–8. https://doi.org/10.15277/bjd.2020.250
Results of the eValuation of ERTugliflozin EffIcacy and Safety CardioVascular Outcomes Trial (VERTIS-CV). Presented on 16 June 2020 during the 80th Scientific Sessions of the American Diabetes Association virtual meeting. Slides available at https://www.acc.org/education-and-meetings/image-and-slide-gallery/media-detail?id=307A7E103BC04A588A3370709253FC35 (accessed 14 October 2020)
Cannon CP, Pratley R, Dagogo‑Jack S, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med 2020;383:1425–35. https://doi.org/10.1056/NEJMoa2004967
EMPEROR-Reduced meets primary endpoint in heart failure with reduced ejection fraction. Report of a Hot Line Session at European Society of Cardiology Congress 2020 – The Digital Experience. https://www.escardio.org/ The-ESC/Press-Office/Press-releases/EMPEROR (accessed 14 October 2020).
Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 2020;383:1413–24. https://doi.org/10.1056/NEJMoa2022190
EASD VIRTUAL MEETING 2020. Webcast: Empagliflozin for the treatment of chronic heart failure and a reduced ejection fraction in patients with and without diabetes: new results of the EMPEROR-Reduced trial. https://www.easd.org/virtualmeeting2020/#!contentsessions/3384 (accessed 14 October 2020).
Strain WD, Holst AG, Rasmussen S, et al. Effects of liraglutide and semaglutide on stroke subtypes in patients with type 2 diabetes: a post hoc analysis of the LEADER, SUSTAIN 6 and PIONEER 6 trials. EASD abstract 258 in OP47 at https://link.springer.com/article/10.1007/s00125-020-05221-5#Sec47 (accessed 15 October 2020). Webcast at https://www.easd.org/virtualmeeting2020/#!resources/effects-of-liraglutide-and-semaglutide-on-stroke-subtypes-in-patients-with-type-2-diabetes-a-post-hoc-analysis-of-the-leader-sustain-6-and-pioneer-6-trials (accessed 15 October 2020).
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347–57. https://doi.org/10.1056/NEJMoa1812389
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. https://doi.org/10.1056/NEJMoa1911303
McGuire DK, Shih WJ, Cosentino F, et al. Association of SGLT2 Inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis. JAMA Cardiol 2020 Oct 7;e204511. https://doi.org/10.1001/jamacardio.2020.4511 [Online ahead of print].
Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR- Reduced and DAPA-HF trials. Lancet 2020;396(10254):819–29. https://doi.org/10.1016/S0140-6736(20)31824-9
Al Jobori H, Daniele G, Adams J, et al. Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients. Diabetes Obes Metab 2017;19:809–13. https://doi.org/10.1111/dom.12881
Komoroski B, Vachharajani N, Boulton D, et al. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther 2009;85:520–6. https://doi.org/10.1038/clpt.2008.251
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes and mortality in type 2 diabetes. N Engl J Med 2015;373:2117–28. http://dx.doi.org/10.1056/NEJMoa1504720
DeFronzo R, Norton L, Abdul-Ghani M. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat Rev Nephrol 2017;13:11–26. https://doi.org/10.1038/nrneph.2016.170
Bailey CJ. EASD VIRTUAL MEETING 2020. Webcast commentary on empagliflozin for the treatment of chronic heart failure and a reduced ejection fraction in patients with and without diabetes: new results of the EMPEROR-Reduced trial. https://www.easd.org/virtualmeeting2020/#!resources/commentary-e5e86c86-9a96-4f71-aee8-665b616ebbb6 (accessed 15 October 2020).
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380:2295–306. https://doi.org/10.1056/NEJMoa1811744
Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med 2020;383:1436–46. https://doi.org/10.1056/NEJMoa2024816
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 2019;394:121–30. https://doi.org/10.1016/S0140-6736(19)31149-3
Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol 2019;7:776–85. https://doi.org/10.1016/S2213-8587(19)30249-9
Ryder REJ. Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit. Diabet Med 2015;32:305–13. http://dx.doi.org/10.1111/dme.12627
Mazzone T, Meyer PM, Feinstein SB, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 2006;296:2572–81. http://dx.doi.org/10.1001/jama.296.21.joc60158
Nissen SE, Nicholls SJ, Wolski K, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 2008;299: 1561–73. http://dx.doi.org/10.1001/jama.299.13.1561
Gautam A, Agrawal PK, Prakash P, Hazra DK. Pioglitazone associated pedal edema resolved by adding sodium glucose co-transporter 2 inhibitor. ADA 76th Scientific Sessions 2016. Late Breaking Poster Session, Poster 140-LB. Abstract 140-LB. Available at https://diabetes.diabetesjournals.org/content/diabetes/suppl/2016/06/20/65.Supplement_1.DC1/2016_ADA_LB_Abstracts_HiRes_FINAL_5_11_16.pdf (accessed 15 October 2020).
Abdul-Ghani MA, Puckett C, Triplitt C, et al. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes Metab 2015;17:268–75. https://doi.org/10.1111/dom.12417
Erdmann E, Charbonnel B, Wilcox RG, et al. Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08). Diabetes Care 2007; 30:2773–8. https://doi.org/10.2337/dc07-0717
Kernan WN, Viscoli CM, Furie KL, et al; IRIS Trial Investigators. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 2016;374: 1321–31. https://doi.org/10.1056/NEJMoa1506930
Wilcox R, Bousser MG, Betteridge DJ, et al. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspectivepioglitAzone Clinical Trial In macroVascular Events 04). Stroke 2007;38:865–73. https://doi.org/10.1161/01.STR.0000257974.06317.49
EASD VIRTUAL MEETING 2020. Webcast: VERTIS-CV outcome. https://www.easd.org/virtualmeeting/home.html#!contentsessions/3380 (accessed 19 Novemberbob 2020).
Oral Semaglutide—The PIONEER Program Trials. Presented on 11 June 2019 during the 79th Scientific Sessions of the American Diabetes Association in San Francisco, USA. Slides available at https://tracs.unc.edu/PIONEER (accessed 12 February 2020).
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