ACADEMIC AND RESEARCH PEER-REVIEWED MEDICAL JOURNALISSN 1727-2378
Ru
En

Glucagon-like Peptide-1 Receptor Agonists: Limitless Potential

DOI:10.31550/1727-2378-2020-19-2-6-12
Bibliography link: Demidova T.Yu., Kozhevnikov A.A. Glucagon-like Peptide-1 Receptor Agonists: Limitless Potential. Doctor.Ru. 2020; 19(2): 6–12. (in Russian) DOI: 10.31550/1727-2378-2020-19-2-6-12
Glucagon-like Peptide-1 Receptor Agonists: Limitless Potential
22 April 07:16

Objective of the Review: To evaluate the mechanisms underlying the glycemic and nonglycemic pleiotropic effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), assess their effectiveness, describe their cardioprotective and nephroprotective effects, and determine the prospects for using these agents in primary prevention.

Key Points: Recent metaanalyses, because of being based on studies with low to moderate heterogeneity, have suggested that cardioprotection is a class effect of GLP-1RA. Treatment with GLP-1RA reduces the rate of hospitalization for chronic heart failure by 8-9% (p<0.03), although the main indication for using these agents is atherosclerotic cardiovascular disease. The nephroprotective effect of GLP-1RA is caused by their reduction of macroalbuminuria. The REWIND trial showed that dulaglutide was associated with a 12% decrease in major unfavorable cardiovascular outcomes in patients, most of whom had no history of cardiovascular disease.

Conclusion: These data broaden our understanding of the cardiovascular effect of GLP-1RA. The REWIND trial demonstrated that GLP-1RA are effective not only for secondary, but also for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus.

Contribution: Demidova, T.Yu. — the concept of the review, a set of clinical material, data processing analysis and interpretation, assistance in writing and editing the article and reviewing critically important content, approval of the manuscript for publication; Kozhevnikov, A.A. — collecting and processing information and writing the article.

Conflict of interest: The authors declare that they do not have any conflict of interests.


T.Yu. Demidova (Corresponding author) — N.I. Pirogov Russian National Research Medical University (a Federal State Autonomous Educational Institution of Higher Education), Russian Ministry of Health; 4 Shkulev St., Bldg. 1, Moscow, Russian Federation 109263. eLIBRARY.RU SPIN: 9600-9796. ORCID: https://orcid.org/0000-0001-6385-540X. Scopus Author ID: 7003771623. E-mail: t.y.demidova@gmail.com

A.A. Kozhevnikov — N.I. Pirogov Russian National Research Medical University (a Federal State Autonomous Educational Institution of Higher Education), Russian Ministry of Health; 4 Shkulev St., Bldg. 1, Moscow, Russian Federation 109263. eLIBRARY.RU SPIN: 3563-0430. ORCID: https://orcid.org/0000-0001-8420-2854. E-mail: kaaruds@yandex.ru

 

Received: 16.03.2020
Accepted: 01.04.2020

Glucagon-like Peptide-1 Receptor Agonists: Limitless Potential
22 April 07:16
LITERATURE
  1. da Silva J.A., de Souza E.C.F., Echazú Böschemeier A.G., da Costa C.C.M., Bezerra H.S., Feitosa E.E.L.C. Diagnosis of diabetes mellitus and living with a chronic condition: participatory study. BMC Public Health. 2018; 699. DOI: 10.1186/s12889-018-5637-9
  2. International Diabetes Federation. IDF Diabetes Atlas. Ninth edition. 2019. URL: https://www.diabetesatlas.org/upload/resources/2019/IDF_Atlas_9th_Edition_2019.pdf (дата обращения — 15.01.2020).
  3. U.S. Department of Health and Human Services Centers for Disease Control and Prevention. National Diabetes Statistics Report 2020. Estimates of diabetes and its burden in the United States. 2020. URL: https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf (дата обращения — 15.01.2020).
  4. Shestakova M.V., Vikulova O.K., Zheleznyakova A.V., Isakov M.A., Dedov I.I. Diabetes epidemiology in Russia: what has changed over the decade? Therapeutic Archive. 2019; 91(10): 4–13. (in Russian). DOI: 10.26442/00403660.2019.10.000364
  5. American Diabetes Association. Diabetes care in the hospital: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020; 43(suppl.1): S1–202. DOI: 10.2337/dc20-S015
  6. Einarson T.R., Acs A., Ludwig C., Panton U.H. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc. Diabetol. 2018; 17(1): 83. DOI: 10.1186/s12933-018-0728-6
  7. Davies M.J., D’Alessio D.A., Fradkin J., Kernan W.N., Mathieu C., Mingrone G. 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): 2669–701. DOI: 10.2337/dci18-0033
  8. Buse J.B., Wexler D.J., Tsapas A., Rossing P., Mingrone G., Mathieu C. et al. 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2020; 63(2): 221–8. DOI: 10.1007/s00125-019-05039-w
  9. Dedov I.I., Shestakova M.V., Mayorov A.Y., eds. Standards of specialized diabetes care. 9th edition. Diabetes Mellitus. 2019; 22(S1): 1–212. (in Russian). DOI: 10.14341/DM221S1
  10. Dedov I.I., Shestakova M.V., Vikulova O.K., Zheleznyakova A.V., Isakov M.А. Diabetes mellitus in Russian Federation: prevalence, morbidity, mortality, parameters of glycaemic control and structure of glucose lowering therapy according to the Federal Diabetes Register, status 2017. Diabetes Mellitus. 2018; 21(3): 144–59. (in Russian). DOI: 10.14341/DM9686
  11. Montvida O., Shaw J., Atherton J.J., Stringer F., Paul S.K. Long-term trends in antidiabetes drug usage in the U.S.: real-world evidence in patients newly diagnosed with type 2 diabetes. Diabetes Care. 2018; 41(1): 69–78. DOI: 10.2337/dc17-1414
  12. Bang C., Mortensen M.B., Lauridsen K.G., Bruun J.M. Trends in antidiabetic drug utilization and expenditure in Denmark: a 22-year nationwide study. Diabetes Obes. Metab. 2020; 22(2): 167–72. DOI: 10.1111/dom.13877
  13. Rehfeld J.F. The origin and understanding of the incretin concept. Front. Endocrinol. (Lausanne). 2018; 9: 387. DOI: 10.3389/fendo.2018.00387
  14. Yabe D., Seino Y., Seino Y. Incretin concept revised: the origin of the insulinotropic function of glucagon‐like peptide‐1 — the gut, the islets or both? J. Diabetes Investig. 2018; 9(1): 21–4. DOI: 10.1111/jdi.12718
  15. Holst J.J. From the incretin concept and the discovery of GLP-1 to today’s diabetes therapy. Front. Endocrinol. (Lausanne). 2019; 10: 260. DOI: 10.3389/fendo.2019.00260
  16. Drucker D.J., Habener J.F., Holst J.J. Discovery, characterization, and clinical development of the glucagon-like peptides. J. Clin. Invest. 127(12): 4217–27. DOI: 10.1172/JCI97233
  17. Holst J.J. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia. 2006; 49(2): 253–60. DOI: 10.1007/s00125-005-0107-1
  18. DeFronzo R.A., Ratner R.E., Han J., Kim D.D., Fineman M.S., Baron A.D. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005; 28(5): 1092–100. DOI: 10.2337/diacare.28.5.1092
  19. Miñambres I., Pérez A. Is there a justification for classifying GLP-1 receptor agonists as basal and prandial? Diabetol. Metab. Syndr. 2017; 9: 6. DOI: 10.1186/s13098-017-0204-6
  20. George C., Byun A., Howard-Thompson A. New injectable agents for the treatment of type 2 diabetes part 2-glucagon-like peptide-1 (GLP-1) agonists. Am. J. Med. 2018; 131(11): 1304–6. DOI: 10.1016/j.amjmed.2018.05.043
  21. Lyseng-Williamson K.A. Glucagon-like peptide-1 receptor agonists in type 2 diabetes: their use and differential features. Clin. Drug Investig. 2019; 39(8): 805–19. DOI: 10.1007/s40261-019-00826-0
  22. Hinnen D. Glucagon-like peptide 1 receptor agonists for type 2 diabetes. Diabetes Spectr. 2017; 30(3): 202–10. DOI: 10.2337/ds16-0026
  23. Cefalu W.T., Kaul S., Gerstein H.C., Holman R.R., Zinman B., Skyler J.S. et al. Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? Reflections from a Diabetes Care editors’ Expert Forum. Diabetes Care. 2018; 41(1): 14–31. DOI: 10.2337/dci17-0057
  24. Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein H.C., Miller M.E., Byington R.P., Goff D.C. Jr, Bigger J.T. et al. Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med. 2008; 358(24): 2545–59. DOI: 10.1056/NEJMoa0802743
  25. ADVANCE Collaborative Group; Patel A., MacMahon S., Chalmers J., Neal B., Billot L. et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 2008; 358(24): 2560–72. DOI: 10.1056/NEJMoa0802987
  26. Duckworth W., Abraira C., Moritz T., Reda D., Emanuele N., Reaven P.D. et al. Glucose control and vascular complications in veterans with type 2 diabetes. N. Engl. J. Med. 2009; 360(2): 129–39. DOI: 10.1056/NEJMoa0808431
  27. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352(9131): 837–53.
  28. Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., Neil H.A.W. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med. 2008; 359(15): 1577–89. DOI: 10.1056/NEJMoa0806470
  29. Husain M., Birkenfeld A.L., Donsmark M., Dungan K., Eliaschewitz F.G., Franco D.R. et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 2019; 381(9): 841–51. DOI: 10.1056/NEJMoa1901118
  30. Del Olmo-Garcia M.I., Merino-Torres J.F. GLP-1 receptor agonists and cardiovascular disease in patients with type 2 diabetes. J. Diabetes Res. 2018; 2018: 4020492. DOI: 10.1155/2018/4020492
  31. Hernandez A.F., Green J.B., Janmohamed S., D'Agostino R.B. Sr, Granger C.B., Jones N.P. et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018; 392(10157): 1519–29. DOI: 10.1016/S0140-6736(18)32261-X
  32. Holman R.R., Bethel M.A., Mentz R.J., Thompson V.P., Lokhnygina Y., Buse J.B. et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 2017; 377(13): 1228–39. DOI: 10.1056/NEJMoa1612917
  33. Pfeffer M.A., Claggett B., Diaz R., Dickstein K., Gerstein H.C., Køber L.V. et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N. Engl. J. Med. 2015; 373(23): 2247–57. DOI: 10.1056/NEJMoa1509225
  34. Li Y., Rosenblit P.D. Glucagon-like peptide-1 receptor agonists and cardiovascular risk reduction in type 2 diabetes mellitus: is it a class effect? Curr. Cardiol. Rep. 2018; 20(11): 113. DOI: 10.1007/s11886-018-1051-2
  35. Bethel M.A., Patel R.A., Merrill P., Lokhnygina Y., Buse J.B., Mentz R.J. et al. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. Lancet Diabetes Endocrinol. 2018; 6(2): 105–13. DOI: 10.1016/S2213-8587(17)30412-6
  36. Kristensen S.L., Rørth R., Jhund P.S., Docherty K.F., Sattar N., Preiss D. 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(10): 776–85. DOI: 10.1016/S2213-8587(19)30249-9
  37. Marsico F., Paolillo S., Gargiulo P., Bruzzese D., Dell'Aversana S., Esposito I. et al. Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials. Eur. Heart J. 2020; pii: ehaa082. DOI: 10.1093/eurheartj/ehaa082
  38. Scheen A.J. GLP-1 receptor agonists and cardiovascular protection: a class effect or not? Diabetes Metab. 2018; 44(3): 193–6. DOI: 10.1016/j.diabet.2017.12.009
  39. Antsiferov M.B., Koteshkova O.M. The role of GLP-1 analogue liraglutide in the treatment of type 2 diabetes. Journal of General Medicine. 2018; 2: 50–8. (in Russian). DOI: 10.24411/2071-5315-2018-12002
  40. Ametov A.S., Nevolnikova A.O., Tertychnaya E.A. Possibilities of glucagon-like peptide-1 receptor agonists in reducing cardiovascular risk in patients with type 2 diabetes mellitus: what's new? Endocrinology: News, Opinions, Education. 2019; 3(28): 44–53. (in Russian). DOI: 10.24411/2304-9529-2019-13005
  41. Scheen A.J. Cardiovascular outcome studies in type 2 diabetes: comparison between SGLT2 inhibitors and GLP-1 receptor agonists. Diabetes Res. Clin. Pract. 2018; 143: 88–100. DOI: 10.1016/j.diabres.2018.06.008
  42. Caruso I., Cignarelli A., Giorgino F. Heterogeneity and similarities in GLP-1 receptor agonist cardiovascular outcomes trials. Trends Endocrinol. Metab. 2019; 30(9): 578–89. DOI: 10.1016/j.tem.2019.07.004
  43. Marso S.P., Bain S.C., Consoli A., Eliaschewitz F.G., Jódar E., Leiter L.A. et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 2016; 375(19): 1834–44. DOI: 10.1056/NEJMoa1607141
  44. Gerstein H.C., Hart R., Colhoun H.M., Diaz R., Lakshmanan M., Botros F.T. et al. The effect of dulaglutide on stroke: an exploratory analysis of the REWIND trial. Lancet Diabetes Endocrinol. 2020; 8(2): 106–14. DOI: 10.1016/S2213-8587(19)30423-1
  45. Marso S.P., Daniels G.H., Brown-Frandsen K., Kristensen P., Mann J.F., Nauck M.A. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 2016; 375(4): 311–22. DOI: 10.1056/NEJMoa1603827
  46. Margulies K.B., Hernandez A.F., Redfield M.M., Givertz M.M., Oliveira G.H., Cole R. et al. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2016; 316(5): 500–8. DOI: 10.1001/jama.2016.10260
  47. Gerstein H.C., Colhoun H.M., Dagenais G.R., Diaz R., Lakshmanan M., Pais P. et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019; 394(10193): 121–30. DOI: 10.1016/S0140-6736(19)31149-3
  48. Williams D.M., Nawaz A., Evans M. Renal outcomes in type 2 diabetes: a review of cardiovascular and renal outcome trials. Diabetes Ther. 2020; 11(2): 369–86. DOI: 10.1007/s13300-019-00747-3
  49. Bethel M.A., Mentz R.J., Merrill P., Buse J.B., Chan J.C., Goodman S.G. et al. Renal outcomes in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). Diabetes. 2018; 67(suppl.1). DOI: 10.2337/db18-522-P
  50. Mann J.F.E., Ørsted D.D., Brown-Frandsen K., Marso S.P., Poulter N.R., Rasmussen S. et al. Liraglutide and renal outcomes in type 2 diabetes. N. Engl. J. Med. 2017; 377(9): 839–48. DOI: 10.1056/NEJMoa1616011
  51. Muskiet M.H.A., Tonneijck L., Huang Y., Liu M., Saremi A., Heerspink H.J.L. et al. Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2018; 6(11): 859–69. DOI: 10.1016/S2213-8587(18)30268-7
  52. Greco E.V., Russo G., Giandalia A., Viazzi F., Pontremoli R., de Cosmo S. GLP-1 receptor agonists and kidney protection. Medicina (Kaunas). 2019; 55(6): pii: E233. DOI: 10.3390/medicina55060233
  53. Nauck M.A., Meier J.J. Management of endocrine disease: are all GLP-1 agonists equal in the treatment of type 2 diabetes? Eur. J. Endocrinol. 2019; 181(6): R211–34. DOI: 10.1530/EJE-19-0566
  54. Gerstein H.C., Colhoun H.M., Dagenais G.R., Diaz R., Lakshmanan M., Pais P. et al. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes. Metab. 2018; 20(1): 42–9. DOI: 10.1111/dom.13028
  55. Gerstein H.C., Colhoun H.M., Dagenais G.R., Diaz R., Lakshmanan M., Pais P. et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019; 394(10193): 131–8. DOI: 10.1016/S0140-6736(19)31150-X
  56. Medication Guide TRULICITY® (TRU-li-si-tee) (dulaglutide) injection, for subcutaneous use. US Food and Drug Administration. Revised. 2020. URL: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125469s033lbl.pdf#page=26 (дата обращения — 15.01.2020).
  57. Instruction for medical use of Trulicity LP-003682. State Register of Medicinal Remedies. URL: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=0a42b385-0ea6-4888-aa42-8410d2051fb0&t= (in Russian)
Similar article
19 May 15:04, Allergology
V.M. Ganuzin, N.L. Chernaya, G.S. Maskova
Features of Specialised Medical Consultation of Adolescents with Bronchial Asthma: Clinical Observation
Doctor.Ru Pediatrics. Vol. 19, No. 3 (2020)
19 May 14:30, Allergology
S.E. Mitskevich, I.A. Fedorov, A.I. Chuprynina, O.G. Rybakova
Use of Omalizumab in Management of Severe Uncontrolled Bronchial Asthma in Children
Doctor.Ru Pediatrics. Vol. 19, No. 3 (2020)

Partners