Treatment with Glucagon-Like Peptide-1 Analogues — a Breakthrough in Diabetes Mellitus Type 2 Therapy


  • V.L. Orlenko State Institution «Institute of Endocrinology and Metabolism named after V.P. Komissarenko of National Academy of Medical Sciences of Ukraine», Kyiv
  • K.P. Zak State Institution «Institute of Endocrinology and Metabolism named after V.P. Komissarenko of National Academy of Medical Sciences of Ukraine», Kyiv



diabetes mellitus, glucagon, insulin, incretins, glucagon-like peptide-1


The paper analyzes the data of modern scientific literature on the new class of drugs that restore the effect of glucagon-like peptide-1 (GLP-1). According to modern concepts, the pathophysio-logical mechanisms of therapeutic action of GLP-1 analogues in patients with diabetes mellitus (DM) type 2 primarily due to their bene-ficial effects on β-cell dysfunction, whose role in the pathogenesis of DM type 2 until recently been underestimated. The main targets of GLP-1 are pancreatic islets, where it glucose-dependently stimulates production and secretion of insulin and somatostatin secretion and inhibits glucagon secretion. Furthermore, GLP-1 inhibits β-cell destruction and stimulates their proliferation, increasing their number. The article presents information on the main multicenter studies on analogues of human GLP-1, analyzes hypoglycemic effectiveness of incretins and others of their positive effects.


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Buse J., Rosenstock J., Sesti G. et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6) // Lancet. — 2009. — V. 374. — P. 39-47.

Гарднер Д., Шобек Д. Базисная и клиническая эндокринология (книга первая). — Москва: Бином, 2010. — С. 264-266.

Leight S., Eicklmann P., Mayet S. Regulation of peptide hormone release from neuroendocrine cells in the gut at the pancreas // Diabetologia. — 2007. — Vol. 50, suppl. 1. — P. 694.

Joanny G., Tellez N., Estiles E. et al. Increased beta cells replication and mass in 95% pancreatectomized rats treated with a DPPIV stabilized GLP-1 analogue // Diabetologia. — 2007. — Vol. 50, suppl. 1. — 0690.

Buse J., Nauck M.A., Forst T. Efficacy and safety of exenatide once weekly versus liraglutide in subjects with type 2 diabetes (DURATION-6): a randomization, open-label study // Diabetologia. — 2011. — Vol. 54, suppl. 1. — 75.

Zhang Z., Yang G., Li L. The effect of liraglutide on metabolism in Apo-/-mice with RNAi-mediated adiponectin gene inhibition // Diabetologia. — 2010. — Vol. 1, suppl. 1. — 636.

Miao Z., Li L., Yang G. Liraglutide attenuated hypoadiponectinaemia-induced deterioration in peripheral and hepatic insulin sensitivity and alterations of gene expression in glucose and lipid metabolism // Diabetologia. — 2011. — Vol. 54, suppl. 1. — 515.

Nauck M., Pratley R. et al. Adding Liraglutide to Existing Therapy ratherthan Substituting it for Existing Therapy Produces Greater Improvement in Glycemic Control: Evidence from a Meta-analysis // 69th ADA Scientific Sessions Abstract Book. — 2009. — Poster 549.

Sokos G.G., Nikolaidis L.A., Mankad S. et al. Glucagon-Like Peptide-1 Infusion Improves Left Ventricular Ejection Fraction and Functional Status in Patients With Chronic Heart Failure // Journal of Cardiac Failure. — 2006. — Vol. 12. — P. 694-699.

Mazzone T., Chait A., Plutzky J. Cardiovascular disease risk in type 2 diabetes mellitus // Lancet. — 2008. — Vol. 24. — P. 1800-1809.

Lorber D. GLP-1 Receptor Agonists: Effects on Cardiovascular Risk Reduction // Cardiovascular Therapeutics. — 2013. — Vol. 31(4). — P. 238-249.

Matthews D.R., Dejager S., Ahren B. et al. Vildagliptin add-on to metformin produces similar efficacy and reduced hypoglycaemic risk compared with glimepiride, with no weight gain: results from a 2-year study // Diab. Obes. Metab. — 2010. — V. 12. — P. 780-789.

Zinman B. et al. Insulin degludec, an ultra-long-acting basal insulin, once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16-week, randomised, open-label, phase 2 trial // Lancet. — 2011. — V. 377. — P. 924-931.

Russell-Jones D. Current developments in the treatment of diabetes: the incretin therapies // British Journal of Diabetes. — 2010. — Vol. 10. — P. 21-30.

Nauck M., Petrie G., Sesti G. et al. The once-weekly human GLP-1 analogue semaglutide provides significant reductions in HbA1c and body weight in patients with type 2 diabetes // Diabetologia. — 2012. — Vol. 55, suppl. 1. — 2.

Meier J.J. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus // Nat. Rev. Endocrinol. — 2012. — V. 8(12). — P. 728-42.

Diamant M., Gaal L.V., Stranks S. Safety and efficacy of once-weekly Exenatide compared with insulin Glargine titrated to Target in patients with Type 2 Diabetes over 84 weeks // Diabetes Care. — 2012. — V. 35. — P. 683-689.

Yki-Järvinen H., Rosenstock J., Durán-Garcia S. et al. Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a ≥ 52-week randomized, double-blind study // Diabetes Care. — 2013. — V. 36(12). — P. 3875-3881.

Ahrén B., Dimas A.L., Miossec P. et al. Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M) // Diabetes Care. — 2013. — doi: 10.2337/dc12-2006.

Cornell S., Dorsey V.J. Diabetes pharmacotherapy in 2012: considerations in medication selection // Postgrad Med. — 2012. — V. 124(4). — P. 84-94.

Umpierrez G.E., Meneghini L. Reshaping diabetes care: the fundamental role of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists in clinical practice // Endocr. Pract. — 2013. — V. 19(4). — P. 718-728.

Aroda V.R., Henry R.R., Han J. et al. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review // Clin. Ther. — 2012. — V. 34(6). — P. 1247-1258.

Lichiardopol R., Florentiu A., Radoi V. Body composition and the metabolic impact of weight excess in patients with type 1 and type 2 diabetes mellitus // Acta Endocr. (Buc). — 2010. — V. 6(4). — P. 493-506.

Grunberger G. Clinical utility of the dipeptidyl peptidase-4 inhibitor linagliptin // Postgrad Med. — 2013. — V. 125(3). — P. 79-90.

Зак К.П., Маньковский Б.Н., Мельниченко С.В. и др. Иммунитет больных сахарным диабетом 2-го типа с сопутствующим метаболическим синдромом/ожирением. Сообщение 2. Роль адипоцитов (интерлейкина-6, фактора некроза опухолей альфа, лептина, адипонектина) // Эндокринология. — 2013. — № 1. — С. 65-78.

Lewin A., Arvay L., Liu D. et al. Efficacy and tolerability of linagliptin added to a sulfonylurea regimen in patients with inadequately controlled type 2 diabetes mellitus: an 18-week, multicenter, randomized, double-blind, placebo-controlled trial // Clin. Ther. — 2012. — V. 34(9). — P. 1909-1919.

Forst T., Lübben G., Hohberg C. Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2 // Microcirculation. — 2005. — 12(7). — P. 543-50.

Fernández-Real J.M., Pickup J.C. Innate immunity, insulin resistance and type 2 diabetes // Diabetologia. — 2012. — V. 55. — P.273-238.

Harrison L.B., Mora P.F., Clark G.O., Lingvay I. Type 1 diabetes treatment beyond insulin: role of GLP-1 analogs // J. Investig. Med. — 2013. — V. 61. — P. 40-44.

Heller S.R. et al. Liraglutide Is a Safe and Beneficial Adjunct to Insulin in Glycemic Control in Type 1 Diabetes-Diabetologia // EASD. — 2013. — abstr. 3; NCT01536665.

Kielgast U., Holst J.J., Madsbad S. Treatment of type 1 diabetic patients with glucagon-like peptide-1 (GLP-1) and GLP-1R agonists // Curr. Diabetes Rev. — 2009. — V. 5(4). — P. 266-275.

Klonoff D.C., Buse J.B., Nielsen L.L. et al. Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years // Curr. Med. Res. Opin. — 2008. — V. 24. — P. 275-286.

Pratley А. et al. Liraglutide compared to sitagliptin, both in combination with metformin, in subjects with type 2 diabetes: a 26-week, randomised, parallel-group, open-label trial // Lancet. — 2010. — 375. — Р. 1447-1456.



How to Cite

Orlenko, V., & Zak, K. (2022). Treatment with Glucagon-Like Peptide-1 Analogues — a Breakthrough in Diabetes Mellitus Type 2 Therapy. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), (4.60), 112–117.



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