Advantages of glucagon-like peptide-1 receptor agonists in the treatment of patients with type 2 diabetes mellitus: A review

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Abstract

Glucagon-like peptide-1 receptor agonists (arGLP1) are an effective treatment for patients with type 2 diabetes mellitus (T2DM), mainly due to increasing insulin secretion and suppressing glucagon release by stimulating the respective receptors. Taking into account their positive effect on major cardiovascular events, drugs in this group with proven cardioprotective effects are recommended for patients with T2DM and clinical cardiovascular diseases or multiple cardiovascular risk factors. In this paper, we present an overview of current clinical studies on the clinical efficacy and safety of arGLP1 and discuss current prospects for arGLP1 as a therapy for patients with T2DM.

About the authors

Tatiana Y. Demidova

Pirogov Russian National Research Medical University

Email: meteora-vica@mail.ru
ORCID iD: 0000-0001-6385-540X

д-р мед. наук, проф., зав. каф. эндокринологии лечебного фак-та

Russian Federation, Moscow

Victoria V. Titova

Pirogov Russian National Research Medical University

Author for correspondence.
Email: meteora-vica@mail.ru
ORCID iD: 0000-0002-8684-6095

ассистент каф. эндокринологии лечебного фак-та

Russian Federation, Moscow

Maryam Y. Izmaylova

Pirogov Russian National Research Medical University

Email: meteora-vica@mail.ru
ORCID iD: 0000-0002-1385-0245

ассистент каф. эндокринологии лечебного фак-та

Russian Federation, Moscow

References

  1. Moberly SP, Mather KJ, Berwick ZC, et al. Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus. Basic Res Cardiol. 2013;108(4):365. doi: 10.1007/s00395-013-0365-x
  2. Panjwani N, Mulvihill EE, Longuet C, et al. GLP-1 receptor activation indirectly reduces hepatic lipid accumulation but does not attenuate development of atherosclerosis in diabetic male ApoE(-/-) mice. Endocrinology. 2013;154(1):127-39. doi: 10.1210/en.2012-1937
  3. Nauck MA, Meier JJ, Cavender MA, et al. Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Circulation. 2017;136:849-70. doi: 10.1161/CIRCULATIONAHA. 117.028136
  4. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-22. doi: 10.1056/NEJMoa1603827
  5. 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):1834-44. doi: 10.1056/NEJMoa1607141
  6. Hernandez AF, Green JB, Janmohamed S, 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
  7. 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):121-30. doi: 10.1016/S0140-6736(19)31149-3
  8. Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N Engl J Med. 2021;385(10):896-907. doi: 10.1056/NEJMoa2108269
  9. Bethel MA, Patel RA, Merrill P, 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
  10. Sattar N, Lee MMY, Kristensen SL, 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 randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653-62. doi: 10.1016/S2213- 8587(21)00203-5
  11. American Diabetes Association. Diabetes Care. 2023;46(suppl. 1):S1-298.
  12. Htike ZZ, Zaccardi F, Papamargaritis D, et al. Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. 2017;19(4):524-36. doi: 10.1111/dom.12849
  13. Verdich C, Flint A, Gutzwiller JP, et al. A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J Clin Endocrinol Metab. 2001;86(9):4382-9. doi: 10.1210/jcem.86.9.7877
  14. Raun K, von Voss P, Knudsen LB. Liraglutide, a once-daily human glucagon-like peptide-1 analog, minimizes food intake in severely obese minipigs. Obesity (Silver Spring). 2007;15(7):1710-6. doi: 10.1038/oby.2007.204
  15. Rowlands J, Heng J, Newsholme P, Carlessi R. Pleiotropic Effects of GLP-1 and Analogs on Cell Signaling, Metabolism, and Function. Front Endocrinol (Lausanne). 2018;9:672. doi: 10.3389/fendo.2018.00672
  16. Vilsbøll T, Christensen M, Junker AE, et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771. doi: 10.1136/bmj.d7771
  17. Tsapas A, Karagiannis T, Kakotrichi P, et al. Comparative efficacy of glucose-lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta-analysis. Diabetes Obes Metab. 2021;23(9):2116-24. doi: 10.1111/dom.14451
  18. Apovian CM, Bergenstal RM, Cuddihy RM, et al. Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes. Am J Med. 2010;123(5):468.e9-e4.68E17. doi: 10.1016/j.amjmed.2009.11.019
  19. DeFronzo RA, Ratner RE, Han J, et al. 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
  20. Buse JB, Henry RR, Han J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004;27(11):2628-35. doi: 10.2337/diacare.27.11.2628
  21. 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):2247-57. doi: 10.1056/NEJMoa1509225
  22. 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):1228-39. doi: 10.1056/NEJMoa1612917
  23. Margulies KB, Hernandez AF, Redfield MM, 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
  24. Margulies KB, Anstrom KJ, Hernandez AF, et al. GLP-1 agonist therapy for advanced heart failure with reduced ejection fraction: design and rationale for the functional impact of GLP-1 for heart failure treatment study. Circ Heart Fail. 2014;7(4):673-9. doi: 10.1161/CIRCHEARTFAILURE.114.000346
  25. Meier JJ, Rosenstock J, Hincelin-Méry A, et al. Contrasting Effects of Lixisenatide and Liraglutide on Postprandial Glycemic Control, Gastric Emptying, and Safety Parameters in Patients With Type 2 Diabetes on Optimized Insulin Glargine With or Without Metformin: A Randomized, Open-Label Trial. Diabetes Care. 2015;38(7):1263-73. doi: 10.2337/dc14-1984
  26. Sattar N, Lee MMY, Kristensen SL, 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 randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653-62. doi: 10.1016/S2213-8587(21)00203-5
  27. Giugliano D, Maiorino MI, Bellastella G, et al. GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta-analysis including the REWIND and PIONEER 6 trials. Diabetes Obes Metab. 2019;21(11):2576-80. doi: 10.1111/dom.13847
  28. Giugliano D, Scappaticcio L, Longo M, et al. GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs. Cardiovasc Diabetol. 2021;20(1):189. doi: 10.1186/s12933-021-01366-8
  29. Giugliano D, Ceriello A, De Nicola L, et al. Primary versus secondary cardiorenal prevention in type 2 diabetes: which newer antihyperglycaemic drug matters? Diabetes Obes Metab. 2020;22:149-57. doi: 10.1111/dom.13881
  30. Giugliano D, Chiodini P, Maiorino MI, et al. Cardiovascular outcome trials and major cardiovascular events: does glucose matter? A systematic review with meta-analysis. J Endocrinol Invest. 2019;42:1165-9. doi: 10.1007/s40618-019-01047-0
  31. Almutairi M, Al Batran R, Ussher JR. Glucagon-like peptide-1 receptor action in the vasculature. Peptides. 2019;111:26-32. doi: 10.1016/j.peptides.2018.09.002
  32. Alicic RZ, Cox EJ, Neumiller JJ, Tuttle KR. Incretin drugs in diabetic kidney disease: biological mechanisms and clinical evidence. Nat Rev Nephrol. 2021;17:227-44. doi: 10.1038/s41581-020-00367-2
  33. Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate- to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018;6(8):605-17. doi: 10.1016/S2213-8587(18)30104-9
  34. Gerstein HC, Colhoun HM, Dagenais GR, 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
  35. Zavattaro M, Caputo M, Samà MT, et al. One-year treatment with liraglutide improved renal function in patients with type 2 diabetes: a pilot prospective study. Endocrine. 2015;50(3):620-6. doi: 10.1007/s12020-014-0519-0
  36. Davies MJ, Bain SC, Atkin SL, et al. Efficacy and Safety of Liraglutide Versus Placebo as Add-on to Glucose-Lowering Therapy in Patients With Type 2 Diabetes and Moderate Renal Impairment (LIRA-RENAL): A Randomized Clinical Trial. Diabetes Care. 2016;39(2):222-30. doi: 10.2337/dc14-2883
  37. Mann JFE, Hansen T, Idorn T, et al. Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1-7 randomised controlled trials. Lancet Diabetes Endocrinol. 2020;8(11):880-93. doi: 10.1016/S2213-8587(20)30313-2
  38. Bethel MA, Mentz RJ, Merrill P, et al. Renal outcomes in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL). Diabetes. 2018;6(Suppl. 1):522. doi: 10.2337/db18-522-P
  39. van der Aart-van der Beek AB, Clegg LE, Penland RC, et al. Effect of once-weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: a post hoc analysis of the EXSCEL trial. Diabetes Obes Metab. 2020;22(12):2493-8. doi: 10.1111/dom.14175
  40. 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):457-66. doi: 10.1111/dom.12244
  41. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28. doi: 10.1056/NEJMoa1504720
  42. Wright AK, Carr MJ, Kontopantelis E, et al. Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes. Diabetes Care. 2022;45(4):909-18. doi: 10.2337/dc21-1113
  43. Gourdy P, Darmon P, Dievart F, et al. Combining glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM). Cardiovasc Diabetol. 2023;22(1):79. doi: 10.1186/s12933-023-01798-4
  44. Wang Y, Li L, Yang M, et al. Glucagon-like peptide-1 receptor agonists versus insulin in inadequately controlled patients with type 2 diabetes mellitus: a meta-analysis of clinical trials. Diabetes, Obes Metab. 2011;13(11):972-81. doi: 10.1111/j.1463-1326.2011.01436.x
  45. Cimmaruta D, Maiorino M, Scavone C, et al. Efficacy and safety of insulin-GLP-1 receptor agonists combination in type 2 diabetes mellitus: a systematic review. Exp Opin Drug Saf. 2016;15(Suppl. 2):77-83. doi: 10.1080/14740338.2016.1221402

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