Ten years of treatment of type 2 diabetes mellitus by gliflozins

Czech version

Authors: Peter Galajda; Matej Samoš; Tomáš Bolek; Simona Horná; Marián Mokáň
Authors‘ workplace: I. interná klinika JLF UK a UNM, Martin
Published in: Forum Diab 2023; 12(2): 76-83
Category:

Overview

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, gliflozins are a modern class of diabetic medications which are used ten years in the treatment of type 2 diabetes mellitus. Apart from good glycemic control, low risk of hypoglycemia and weight loss, gliflozins have been shown to provide significant cardiovascular and nephroprotective benefit in patients with type 2 diabetes mellitus. Adverse side effects include increased risk of urinary infections, mainly vaginal candidosis euglycemic ketoacidosis, volume depletion with hypotension, which are considered to be a class effect of gliflozins. According to international standards gliflozins can be indicated such drugs of first choice in the treatment of type 2 diabetic patients with high cardiovascular risk.

Keywords:

gliflozins – adverse effect – cardiovascular and nephroprotective benefit – euglycemic ketoacidosis – sodium-glucose co-transporter 2 (SGLT2) inhibitors- type 2 diabetes mellitus – urinary infections – vaginal candidosis – volume depletion with hypotension

Sources

1. Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGFLT2 inhibition. Diabetologia 2017; 60(2): 215–225. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125–016–4157–3>.

2. Monami M, Nardini C, Mannucci E. Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab 2014; 16(5): 457–466. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12244>.

3. Kuchay MS, Krishan S, Mishra SK et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: A randomized controlled trial (E-LIFT Trial). Diabetes Care 2018; 41(8): 1801–1808. Dostupné z DOI: <http://dx.doi.org/10.2337/dc18–0165>.

4. Xu L, Nagata N, Nagashimada M et al. SGLT2 inhibition by empagliflozin promotes fat utilization and browning and attenuates inflammation and insulin resistance by polarizing M2 macrophages in diet-induced obese mice. EBioMedicine 2017; 20: 137–149. Dostupné z DOI: <http://dx.doi.org/10.1016/j.ebiom.2017.05.028>.

5. Bonnet F, Scheen AJ. Effects of SGLT2 inhibitors on systemic and tissue low-grade inflammation: The potential contribution to diabetes complications and cardiovascular disease. Diabetes Metab 2018; 44(6): 457–464. Dostupné z DOI: <http://dx.doi.org/10.1016/j.diabet.2018.09.005>.

6. Martinka E, Mokáň M, Rašlová K et al. Interdisciplinárne štandardy diagnostiky a liečby diabetes mellitus, jeho komplikácií a najvýznamnejších sprievodných ochorení – 2021. Forum Diab 2021; 10(Suppl 2): 4–279.

7. ElSayed NA, Aleppo G, Aroda VR et al. [American Diabetes Association]. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes – 2023. Diabetes Care 2023; 46(Suppl 1): S140–S157. Dostupné z DOI: <http://dx.doi.org/10.2337/dc23-S009>.

8. 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(22): 2117–2128. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1504720>.

9. 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(7): 644–657.Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1611925>.

10. Wiviott SD, Raz I, Bonaca MP et al. [DECLARE–TIMI 58 Investigators]. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380(4): 347–357.Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1812389>.

11. 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 (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter- 2 Inhibitors) Circulation 2017; 136(3): 249–259. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.117.029190>.

12. 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: <http://dx.doi.org/10.1111/dom.13424>.

13. 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: <http://dx.doi.org/10.1161/CIRCULATIONAHA.118.039177>.

14. Packer M, Anker SD, Butler Jet 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: <http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051783>.

15. McMurray JJ, Solomon SD, Inzucchi SEet 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: <http://dx.doi.org/10.1056/NEJMoa1911303>.

16. 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: <http://dx.doi.org/10.1161/CIRCULATIONAHA.121.056824>.

17. 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; 80(14): 1302–1310. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2022.07.021>.

18. FDA Drug Safety Communication. FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) [06–14–2016]. Dostupné z WWW: <https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-strengthens-kidney-warnings-diabetes-medicines-canagliflozin>.

19. 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: <http://dx.doi.org/10.1056/NEJMoa1811744>.

20. Mahaffey KW, Jardine MJ, Bompoint S et al. Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes and chronic kidney disease in primary and secondary cardiovascular prevention groups: results from the randomized CREDENCE trial. Circulation 2019; 140(9): 739–750. Dostupné z DOI: <http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042007>.

21. 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: <http://dx.doi.org/10.1016/S2213–8587(20)30369–7>.

22. Herrington WG, Staplin N, Wanner C et al. [EMPA-KIDNEY Collaborative Group]. Empagliflozin in patients with chronic kidney disease. N Engl J Med 202; 388(2): 117–127. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa2204233>.

23. Forxiga (dapagliflozín). Súhrn charakteristických vlastností lieku. Dostupné z WWW: <https://www.ema.europa.eu/en/documents/referral/forxiga-article-20-procedure-annex-i-iii_sk.pdf>.

24. Invokana (kanagliflozín). Súhrn charakteristických vlastností lieku. Dostupné z WWW: <https://www.ema.europa.eu/en/documents/product-information/invokana-epar-product-information_sk.pdf>.

25. Jardiance (empagliflozín). Súhrn charakteristických vlastností lieku. Dostupné z WWW: <https://www.ema.europa.eu/en/documents/product-information/jardiance-epar-product-information_sk.pdf>.

26. FDA Drug Safety Communication. FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. Dostupné z WWW: <https://www.fda.gov/drugs/drug-safety-and-availability/fda-revises-labels-sglt2-inhibitors-diabetes-include-warnings-about-too-much-acid-blood-and-serious>

27. Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: A predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care 2015; 38 (9): 1638–1642. Dostupné z DOI: <http://dx.doi.org/10.2337/dc15–1380>.

28. Peters AL, Buschur EO, Buse JB. Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care 2015; 38(9): 1687–1693. Dostupné z DOI: <http://doi/10.2337/dc15–0843>.

29. FDA Drug Safety Communication. FDA warns about rare occurrences of a serious infection of the genital area with SGLT2 inhibitors for diabetes [8–29–2018]. <https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-rare-occurrences-serious-infection-genital-area-sglt2-inhibitors-diabetes>.

30. FDA Drug Safety Communication [05–16–2017]. Interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA to investigate. <https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-interim-clinical-trial-results-find-increased-risk-leg-and-foot>.

31. [EMA]. SGLT2 inhibitors: information on potential risk of toe amputation to be included in prescribing information. Dostupné z WWW: <https://www.ema.europa.eu/en/news/sglt2-inhibitors-information-potential-risk-toe-amputation-be-included-prescribing-information>.

32. Inzucchi SE, Iliev H, Pfarr E et al. Empagliflozin and assessment of lower-limb amputations in the EMPA-REG OUTCOME trial. Diabetes Care 2018; 41(1): e4-e5. Dostupné z DOI: <http://dx.doi.org/10.2337/dc17–1551>.

33. Verma S, Mazer CD, Al-Omran M et al. Cardiovascular outcomes and safety of empagliflozin in patients with type 2 diabetes mellitus and peripheral artery disease. A subanalysis of EMPA-REG OUTCOME. Circulation 2018; 137(4): 405–407. <http://dx.doi.org/10.1161/CIRCULATIONAHA.117.032031>.

34. Tkáč I. Amputácie dolných končatín u pacientov s diabetom a inhibítory SGLT-2. Interná Med 2018; 18(2): 61–64.

35. Janssen Research & Development LLC. (Posted 2016). Sodium-glucose Co-transporter 2 (SGLT2) Inhibitor Risk of Below-Knee Lower Extremity Amputation: A Retrospective Cohort Study Using a Large Claims Database in the United States (NCT02857764). Dostupné z WWW: <https://clinicaltrials.gov/ct2/show/study/NCT02857764>.

36. Lin HW, Tseng CH. A Review on the relationship between SGLT2 Inhibitors and cancer. Int J Endocrinol 2014; 2014: 719578. Dostupné z DOI: <http://dx.doi.org/10.1155/2014/719578>.

37. .Dicembrini I, Nreu B, Mannucci E et al. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors and cancer: A meta-analysis of randomized controlled trials. Diabetes Obes Metab 2019; 21(8): 1871–1877. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.13745>.

38. Li YR, Liu CH, Sun WC et al. The Risk of Bladder Cancer in Type 2 Diabetes Mellitus with Combination Therapy of SGLT-2 Inhibitors and Pioglitazone. J Pers Med 2021; 11(9):828. Dostupné z DOI: <http://dx.doi.org/10.3390/jpm11090828>.

39. Tang H, Yang K, Song Y et al. Meta-analysis of the association between sodium-glucose co-transporter-2 inhibitors and risk of skin cancer among patients with type 2 diabetes. Diabetes Obes Metab 2018; 20(12): 2919–2924. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.13474>.

Labels

Diabetology Endocrinology Internal medicine

Diabetes mellitus ako súčasť kardio-nefro-hepato-endokrinnometabolického syndrómu v svetle nových odporúčaní

Metabolic syndrome and chronic kidney disease

Metabolic syndrome and non-alcoholic fatty liver disease

Low grade inflammatory reaction in pathogenesis of metabolic syndrome

Odporúčané postupy pre liečbu diabetes mellitus 2. typu – 2023

Article was published in

Forum Diabetologicum

2023 Issue 2