Incretin-based treatment of diabetes and cardiovascular complications

Česká verzia

Authors: Martin Haluzík
Authors place of work: Centrum diabetologie IKEM a ÚLBLD 1. LF UK a VFN, Praha
Published in the journal: Vnitř Lék 2020; 66(2): 74-80
Category: Main Topic

Summary

Cardiovascular complications are main cause of increased mortality in patients with type 2 diabetes. Decrease of overall cardiovascular risk and subsequently cardiovascular morbidity and mortality in type 2 diabetes patients is therefore an important treatment aim. To this end, intensive intervention of classical risk factors such as dyslipidemia, arterial hypertension, smoking along with lifestyle intervention is necessary. Good diabetes control optimally with the use of antidiabetic medication and smoking with positive effect on cardiovascular complication is of high importance as well.

Incretin-based therapy includes an approach based on an increase of endogenous GLP-1 concentrations by inhibition of its breakdown by dipeptidyl-peptidase 4 (DPP-4 inhibitors or gliptins) or he use of GLP-1 receptor agonists that owing to modified structure have much longer half-life than endogenous GLP-1 and act the use through stimulation of GLP-1 receptor.

The aim of this paper is to summarize the use of these two groups of antidiabetic drugs – gliptins and GLP-1 receptor agonists – in patients with type 2 diabetes focusing on the their cardiovascular effects and their influence on cardiovascular complications.

Keywords:

type 2 diabetes mellitus – cardiovascular complications – incretin‑based therapy – gliptins – GLP-1 receptor agonists

Zdroje

1. O‘Rahilly S. Science, medicine, and the future. Non‑insulin dependent diabetes mellitus: the gathering storm. Bmj. 1997; 314(7085): 955–959.

2. Bluher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract Res Clin Endocrinol Metab. 2013; 27(2): 163–177.

3. Reaven G, Abbasi F, McLaughlin T. Obesity, insulin resistance, and cardiovascular disease. Recent Prog Horm Res. 2004; 59: 207–223.

4. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998; 339(4): 229–234.

5. Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017.

6. Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2011; 34(5): 1164–1170.

7. Nauck MA. Glucagon‑like peptide 1 (GLP-1) in the treatment of diabetes. Horm Metab Res. 2004; 36(11–12): 852–858.

8. Davies MJ, D‘Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018; 41(12): 2669–2701.

9. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow‑up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359(15): 1577–1589.

10. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009; 360(2): 129–139.

11. Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials: a position statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association. J Am Coll Cardiol. 2009; 53(3): 298–304.

12. Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascu‑ lar outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358(24): 2560–2572.

13. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358(24): 2545–2559.

14. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007; 356(24): 2457–2471.

15. Buse JB, Wexler DJ, Tsapas A, et al. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2020; 43(2): 487–493.

16. Holst JJ, Deacon CF, Vilsboll T, Krarup T, Madsbad S. Glucagon‑like peptide-1, glucose homeostasis and diabetes. Trends Mol Med. 2008; 14(4): 161–168.

17. Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004; 287(2): E199–206.

18. Holst JJ, Deacon CF. Inhibition of the activity of dipeptidyl‑peptidase IV as a treatment for type 2 diabetes. Diabetes. 1998; 47(11): 1663–1670.

19. Scheen AJ. Safety of dipeptidyl peptidase-4 inhibitors for treating type 2 diabetes. Expert Opin Drug Saf. 2015; 14(4): 505–524.

20. Strain WD, Lukashevich V, Kothny W, Hoellinger MJ, Paldanius PM. Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add‑on or lone therapy (INTERVAL): a 24 week, randomised, double‑blind, placebo‑controlled study. Lancet. 2013;382(9890): 409–416.

21. Mundra V. Evaluation of vildagliptin and fixed dose combination of vildagliptin and metformin on glycemic control and insulin dose over three months in patients with type 2 diabetes mellitus‘. Indian J Endocrinol Metab. 2012; 16(6): 1048.

22. Madsbad S. Exenatide and liraglutide: different approaches to develop GLP-1 recep‑ tor agonists (incretin mimetics) – preclinical and clinical results. Best Pract Res Clin Endocrinol Metab. 2009; 23(4): 463–477.

23. Madsbad S, Kielgast U, Asmar M, Deacon C, Torekov SS, Holst JJ. An overview of once‑weekly GLP-1 receptor agonists – available efficacy and safety data and perspectives for the future. Diabetes Obes Metab. 2011.

24. Kuritzky L, Umpierrez G, Ekoe JM, Mancillas‑Adame L, Lando LF. Safety and efficacy of dulaglutide, a once weekly GLP-1 receptor agonist, for the management of type 2 diabetes. Postgrad Med. 2014; 126(6): 60–72.

25. Montanya E, Sesti G. A review of efficacy and safety data regarding the use of liraglu‑ tide, a once‑daily human glucagon‑like peptide 1 analogue, in the treatment of type 2 diabetes mellitus. Clin Ther. 2009; 31(11): 2472–2488.

26. Pyke C, Heller RS, Kirk RK, et al. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology. 2014; 155(4): 1280–1290.

27. Aaboe K, Krarup T, Madsbad S, Holst JJ. GLP-1: physiological effects and potential the‑ rapeutic applications. Diabetes Obes Metab. 2008; 10(11): 994–1003.

28. Arakawa M, Mita T, Azuma K, et al. Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon‑like peptide-1 receptor agonist, exendin-4. Diabetes. 2010; 59(4): 1030–1037.

29. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013; 369(14): 1317–1326.

30. Green JB, Bethel MA, Armstrong PW, et al. Effect of Sitagliptin on Cardiovascular Out‑ comes in Type 2 Diabetes. N Engl J Med. 2015; 373(3): 232–242.

31. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in pa‑ tients with type 2 diabetes. N Engl J Med. 2013; 369(14): 1327–1335.

32. Rosenstock J, Perkovic V, Johansen OE, et al. Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial. JAMA. 2019; 321(1): 69–79.

33. Tella SH, Rendell MS. DPP-4 inhibitors: focus on safety. Expert Opin Drug Saf. 2015; 14(1): 127–140.

34. Cosentino F, Grant PJ, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre‑diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41(2): 255–323.

35. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med. 2015; 373(23): 2247–2257.

36. Marso SP, Daniels GH, Brown‑Frandsen K, et al. Liraglutide and Cardiovascular Outco‑ mes in Type 2 Diabetes. N Engl J Med. 2016; 375(4): 311–322.

37. Holman RR, Bethel MA, Mentz RJ, et al. Effects of Once‑Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2017; 377(13): 1228–1239.

38. Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016; 375(19): 1834–1844.

39. 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(10193): 121–130.