Long term protective effects of empagliflozine in whole spectrum of patients with type 2 diabetes mellitus from early stages of disease

Czech version

Authors: Peter Galajda; Matej Samoš; Tomáš Bolek; Marián Mokáň
Authors‘ workplace: I. interná klinika JLF UK a UNM, Martin
Published in: Forum Diab 2024; 13(1): 31-36

Overview

Empagliflozine belongs to group of sodium-glucose co-transporter 2 (SGLT2) inhibitors, a modern class of diabetic medications which is used ten years on European market in the treatment of type 2 diabetes mellitus. Apart from good glycemic control, low risk of hypoglycemia and weight loss, empagliflozine has been shown to provide significant benefit on other components of cardiovascular-kidney-metabolic syndrome. Reduction of hospitalizations due to chronic and acute heart failure was confirmed in clinical randomized studies. Treatment is associated with decreased progression of chronic kidney disease, including prolonged time to initiating of hemodialysis treatment. Cardio-renal benefit on heart failure and prevention of progression on chronic kidney disease was confirmed also in non-diabetic patients. According to international standards gliflozines are recommended as first choice in treatment of patients with type 2 diabetes and high cardiovascular risk including those with established cardiovascular disease, heart failure or chronic kidney disease. Long term usage of gliflozines from early stages of disease could be associated with reduced risk of diabetic kidney disease.

Keywords:

type 2 diabetes mellitus – sodium-glucose co-transporter-2 (SGLT2) inhibitors – cardiovascular and nephroprotective benefit – cardiovascular-kidney-metabolic syndrome – empagliflozine

Sources

Ndumele CE, Neeland IJ, Tuttle KR et al. [American Heart Association]. A synopsis of the evidence for the science and clinical management of Cardiovascular-Kidney-Metabolic (CKM) syndrome: A scientific statement from the American Heart Association. Circulation 2023; 148(20): 1636–1664. Dostupné z DOI: <https://doi.org/10.1161/CIR.0000000000001186>.

Martinka E, Mokáň M, Rašlová K, Tkáč I, Schroner Z, Galajda P et al. Interdisciplinárne štandardy diagnostiky a liečby diabetes mellitus, jeho komplikácií a najvýznamnejších sprievodných ochorení – 2021. Forum Diab 2021; 10 (S2): 4–279.

Martinka E, Tkáč I, Mokáň M, Fábryová Ľ, Galajda P et al. Odporúčané postupy pre liečbu diabetes mellitus 2. typu – 2023. Forum Diab 2023; 12(2): 93–133.

Zinman B, Wanner C, Lachin JM et al. [EMPAREG-OUTCOME Investigators]. Empagliflozine, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117–2128. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1504720>.

Neal B, Perkovic V, Mahaffey KW et al. [CANVAS Program Collaborative Group]. Canagliflozine and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644–657. Dostupné z DOI: <https://doi.org/10.1056/NEJMc1712572>.

Wiviott SD, Raz I, Bonaca MP et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380: 347–357. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa181238>.

Kosiborod M, Cavender MA, Fu AZ et al. Lower risk of heart Failure and death in patients initiated on SGLT-2 inhibitors versus other glucose-lowering drugs: The CVD-REAL study. Circulation 2017; 136(3): 249–259. Dostupné z DOI: <https://doi.org/10.1161/CIRCULATIONAHA.117.029190>.

Ryan P, Buse JB, Schuemie MJ et al. Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D). Diabetes Obes Metab 2018; 20(11): 2585–2597. Dostupné z DOI: <https://doi.org/10.1111/dom.13424>.

Patorno E, Pawar A, Franklin JM et al. Empagliflozin and the risk of heart failure hospitalization in routine clinical care: a first analysis from the empagliflozin comparative effectiveness and safety (EMPRISE) Study. Circulation 2019; 139(25): 2822–2830. Dostupné z DOI: <https://doi.org/10.1161/CIRCULATIONAHA.118.039177>.

Packer M, Anker SD, Butler J et al. Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: The EMPEROR-Reduced Trial. Circulation 2021; 143(4): 326–336. Dostupné z DOI: <https://doi.org/10.1161/CIRCULATIONAHA.120.051783>.

Packer M, Butler J, Zannad F et al. Effect of empagliflozin on worsening heart failure events in patients with heart failure and preserved ejection fraction: EMPEROR-Preserved Trial. Circulation 2021; 144(16): 1284–1294. Dostupné z DOI: <https://doi.org/10.1161/CIRCULATIONAHA.121.056824>.

Filippatos G, Farmakis D, Butler J et al. [EMPEROR-Preserved Trial Committees and Investigators]. Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillation. Eur J Heart Fail 2023; 25(7): 970–977. Dostupné z DOI: <https://doi.org/10.1002/ejhf.2861>.

Butler J, Usman MS, Filippatos G et al. Safety and efficacy of empagliflozin and diuretic use in patients with heart Failure and preserved ejection fraction: A post hoc snalysis of the EMPEROR-Preserved Trial. JAMA Cardiol 2023; 8(7): 640–649. Dostupné z DOI: <https://doi.org/10.1001/jamacardio.2023.1090>.

McMurray JJV, Solomon SD, Inzucchi SE et al. DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart Failure and reduced ejection fraction. N Engl J Med 2019; 381(21): 1995–2008. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1911303>.

Cunningham JW, Vaduganathan M, Claggett BL et al. Dapagliflozin in patients recently hospitalized with heart failure and mildly reduced or preserved ejection fraction. J Am Coll Cardiol 2022; 80(14): 1302–1310. Dostupné z DOI: <https://doi.org/10.1016/j.jacc.2022.07.021>.

Voors AA, Angermann CE, Teerlink JR et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med 2022; 28(3): 568–574. Dostupné z DOI: <https://doi.org/10.1038/s41591–021–01659–1>.

McGuire DK, Zinman B, Inzucchi SE et al. Effects of empagliflozin on first and recurrent clinical events in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a secondary analysis of the EMPA-REG OUTCOME trial. Lancet Diabetes Endocrinol 2020; 8: 949–959. Dostupné z DOI: <https://doi.org/10.1016/S2213–8587(20)30344–2>.

Perkovic EV, Jardine MJ, Neal B et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380 (24): 2295–2306. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa1811744>.

Wheeler DC, Stefánsson BV, Jongs N et al. DAPA-CKD Trial Committees and Investigators. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021; 9(1): 22–31. Dostupné z DOI: <https://doi.org/10.1016/S2213–8587(20)30369–7>.

Herrington WG, Staplin N, Wanner et al. The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med 2022; 388(2): 117–127. Dostupné z DOI: <https://doi.org/10.1056/NEJMoa2204233>.

Fernández-Fernandez B, Sarafidis P, Soler MJ, Ortiz A. EMPA-KIDNEY: expanding the range of kidney protection by SGLT2 inhibitors. Clin Kidney J 2023; 16(8): 1187–1198. Dostupné z DOI: <https://doi.org/10.1093/ckj/sfad082>.

Malzer-Cohen C, Schechter M, Rozenberg A et al. Long-term, Real-World kidney outcomes with SGLT2i versus DPP4i in type 2 diabetes without cardiovascular or kidney disease. Clin J Am Soc Nephrol 2023; 18(9): 1153–1162. Dostupné z DOI: <https://doi.org/10.2215/CJN.0000000000000218>.

Green JB, Mottl AK, Bakris G et al. Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE). Nephrol Dial Transplant 2023; 38(4): 894–903. Dostupné z DOI: <https://doi.org/10.1093/ndt/gfac198>.

American Diabetes Association. Pharmacologic approaches to glycemic treatment: Standards of care in diabetes—2024. Diabetes Care 2024; 47(Supl 1): S158–S178. Dostupné z DOI: <https://doi.org/10.2337/dc24-S009>.

Balasubramanian P, Wanner C, Ferreira JP et al. Empagliflozin and decreased risk of nephrolithiasis: A potential new role for SGLT2 inhibition? J Clin Endocrinol Metab 2022; 107(7): e3003-e3007. Dostupné z DOI: <https://doi.org/10.1210/clinem/dgac154>.

Refardt J, Imber C, Nobbenhuis R et al. Treatment effect of the SGLT2 inhibitor empagliflozin on chronic syndrome of inappropriate antidiuresis: Results of a randomized, double-blind, placebo-controlled, crossover Trial. J Am Soc Nephrol 2023; 34(2): 322–332. Dostupné z DOI: <https://doi.org/10.1681/ASN.2022050623>.

Wu W, Wang Y, Xie J, Fan S. Empagliflozin: a potential anticancer drug. Discov Oncol 2023; 14(1): 127. Dostupné z DOI: <https://doi.org/10.1007/s12672–023–00719-x>.

Labels

Diabetology Endocrinology Internal medicine

Ikaros, blood pressure and diabetes mellitus and the dangers of flying too close to the sun

Telemedicine in outpatient diabetes practice

Blood pressure and cardiovascular risk prediction in patients with diabetes mellitus: an introduction

New recommendations for arterial hypertension management and blood pressure targets for type 2 diabetes mellitus

Treatment with beta-blockers and nebivolol in the light of new recommendations: conclusions from the 32nd Congress ESH Milan 2023

Metformin in patients with psoriasis

What news in obesity management did 2023 bring us?

Folistatin and type 2 diabetes mellitus

Article was published in

Forum Diabetologicum

2024 Issue 1