Физиология, фармакология и перспективы применения ингибиторов дипептидилпептидазы-4

Современные требования к терапии сахарного диабета 2 типа (СД 2) включают не только достижение гликемического контроля, но и снижение риска развития сердечно-сосудистых осложнений. Ингибиторы дипептидилпептидазы 4 (ДПП-4) уступают по эффективности некоторым другим активно развивающимся группам гипогликемических препаратов (ингибиторы SGLT2 и агонисты рецепторов ГПП-1), однако представляются актуальными и в настоящее время.

Цель. Проанализировать данные литературы о терапевтическом потенциале и результатах исследований ингибиторов ДПП-4.

Материалы и методы. При поиске материала для написания обзорной статьи использовали реферативные базы PubMed, Google Scholar и e-Library. Поиск осуществлялся по публикациям за период с 2006 по 2022 год, с использованием следующих ключевых слов: ингибиторы ДПП-4; глюкагоноподобный пептид-1 (ГПП-1); глюкозозависимый инсулинотропный пептид (ГИП); ситаглиптин и другие препараты.

Результаты. ДПП-4 принадлежит к семейству сериновых протеаз и участвует в деградации некоторого количества хемокинов и пептидных гормонов, в том числе и инкретинов, секретируемых L- и K-клетками кишечника: ГПП-1 и ГИП, которые регулируют постпрандиальную секрецию инсулина и функцию β-клеток, модулируют тощаковую и постпрандиальную секрецию глюкагона, регулируют пищевое поведение и оказывают множество плейотропных эффектов (иммуномодулирующее, противовоспалительное, антифибротическое действие и др.). Ингибиторы ДПП-4 снижают активность фермента на 70–90%, повышая уровень инкретинов в плазме в 2–4 раза и применяются для лечения СД 2 с 2006 года. Сейчас на рынке разных стран присутствуют 13 ингибиторов ДПП-4, различающихся прежде всего фармакокинетическими параметрами. Они активно используются в комбинированной терапии СД 2, повышая эффективность гликемического контроля без увеличения риска развития гипогликемии. Появляются данные о терапевтическом потенциале ингибиторов ДПП-4 при COVID-19.

Заключение. Пероральная форма, возможность создавать эффективные комбинации с другими гипогликемическими препаратами без увеличения риска гипогликемии, плейотропные эффекты ингибиторов ДПП-4 делают данную группу актуальной и в настоящее время.

1. Дедов И.И., Шестакова М.В., Майоров А.Ю., Мокрышева Н.Г., Викулова О.К., Галстян Г.Р., Кураева Т.Л., Петеркова В.А., Смирнова О.М., Старостина Е.Г., Суркова Е.В., Сухарева О.Ю., Токмакова А.Ю., Шамхалова М.Ш., Ярек-Мартынова И.Я., Артемова Е.В., Бешлиева Д.Д., Бондаренко О.Н., Волеводз Н.Н., Гомова И.С., Григорян О.Р., Джемилова З.Н., Есаян Р.М., Ибрагимова Л.И., Калашников В.Ю., Кононенко И.В., Лаптев Д.Н., Липатов Д.В., Мельникова О.Г., Михина М.С., Мичурова М.С., Мотовилин О.Г., Никонова Т.В., Роживанов Р.В., Скляник И.А., Шестакова Е.А. «Алгоритмы специализированной медицинской помощи больным сахарным диабетом». Под редакцией И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. 10-й выпуск // Сахарный диабет. – 2021. – Т. 24, № 1S. – С. 1–148.DOI:10.14341/DM12802

2. Sun H., Saeedi P., Karuranga S., Pinkepank M., Ogurtsova K., Duncan B.B., Stein C., Basit A., Chan J.C.N., Mbanya J.C., Pavkov M.E., Ramachandaran A., Wild S.H., James S., Herman W.H., Zhang P., Bommer C., Kuo S., Boyko E.J., Magliano D.J. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045 // Diabetes Res. Clin. Pract. – 2022. – Vol. 183. – Art. ID: 109119. DOI:10.1016/j.diabres.2021.109119

3. Hu Y., Chen Y. Overview of Type 2 Diabetes Drugs on the Market // J. Biosci. Med. – 2020. – Vol. 8, No. 8. – P. 1–14. DOI:10.4236/jbm.2020.88001.

4. Röhrborn D., Wronkowitz N., Eckel J. DPP4 in Diabetes // Front. Immunol. – 2015. – Vol. 6. – Art. ID: 386. DOI:10.3389/fimmu.2015.00386

5. Drucker D.J. Dipeptidyl peptidase-4 inhibition and the treatment of type 2 diabetes: preclinical biology and mechanisms of action // Diabetes Care. – 2007. – Vol. 30, No. 6. – P. 1335–1343. DOI:10.2337/dc07-0228

6. Nabeno M., Akahoshi F., Kishida H., Miyaguchi I., Tanaka Y., Ishii S., Kadowaki T. A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site // Biochem. Biophys. Res. Commun. – 2013. – Vol. 434, No. 2. – P. 191–196. DOI:10.1016/j.bbrc.2013.03.010

7. Matteucci E., Giampietro O. Dipeptidyl peptidase-4 (CD26): knowing the function before inhibiting the enzyme // Curr. Med. Chem. – 2009. – Vol. 16, No. 23. – P. 2943–2951. DOI:10.2174/092986709788803114

8. Saisho Y. Incretin-based therapy and pancreatitis: accumulating evidence and unresolved questions // Ann. Transl. Med. – 2018. – Vol. 6, No. 7. – Art. ID: 131. DOI:10.21037/atm.2018.02.24

9. Kubota S., Haraguchi T., Kuwata H., Seino Y., Murotani K., Tajima T., Terashima G., Kaneko M., Takahashi Y., Takao K., Kato T., Shide K., Imai S., Suzuki A., Terauchi Y., Yamada Y., Seino Y., Yabe D. Association of dipeptidyl peptidase-4 inhibitor use and risk of pancreatic cancer in individuals with diabetes in Japan // J. Diabetes Investig. – 2023. – Vol. 14, No. 1. – P. 67–74. DOI:10.1111/jdi.13921

10. Dicembrini I., Montereggi C., Nreu B., Mannucci E., Monami M. Pancreatitis and pancreatic cancer in patients treated with Dipeptidyl Peptidase-4 inhibitors: An extensive and updated meta-analysis of randomized controlled trials // Diabetes Res. Clin. Pract. – 2020. – Vol. 159. – Art. ID: 107981. DOI:10.1016/j.diabres.2019.107981

11. Shao S., Xu Q., Yu X., Pan R., Chen Y. Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions // Pharmacol. Ther. – 2020. – Vol. 209. – Art. ID: 107503. DOI:10.1016/j.pharmthera.2020.107503

12. Mentlein R. Mechanisms underlying the rapid degradation and elimination of the incretin hormones GLP-1 and GIP // Best Pract. Res. Clin. Endocrinol. Metab. – 2009. – Vol. 23, No. 4. – P. 443–452. DOI:10.1016/j.beem.2009.03.005

13. Duez H., Cariou B., Staels B. DPP-4 inhibitors in the treatment of type 2 diabetes // Biochem. Pharmacol. – 2012. – Vol. 83, No. 7. – P. 823–832. DOI:10.1016/j.bcp.2011.11.028

14. Uto A., Miyashita K., Endo S., Sato M., Ryuzaki M., Kinouchi K., Mitsuishi M., Meguro S., Itoh H. Transient Dexamethasone Loading Induces Prolonged Hyperglycemia in Male Mice With Histone Acetylation in Dpp-4 Promoter // Endocrinology. – 2021. – Vol. 162, No. 12. – P. bqab193. DOI:10.1210/endocr/bqab193. Erratum in: Endocrinology. – 2022. – Vol. 163, No. 11.

15. Kosaraju J., Holsinger R.M.D., Guo L., Tam K.Y. Linagliptin, a Dipeptidyl Peptidase-4 Inhibitor, Mitigates Cognitive Deficits and Pathology in the 3xTg-AD Mouse Model of Alzheimer’s Disease // Mol. Neurobiol. – 2017. – Vol. 54, No. 8. – P. 6074–6084. DOI:10.1007/s12035-016-0125-7

16. Avogaro A., Fadini G.P. The pleiotropic cardiovascular effects of dipeptidyl peptidase-4 inhibitors // Br. J. Clin. Pharmacol. – 2018. – Vol. 84, No. 8. – P. 1686–1695. DOI:10.1111/bcp.13611

17. Бирюкова Е.В., Шинкин М.В. Практика сахароснижающей терапии: выбор оптимального препарата из группы ингибиторов дипептидилпептидазы 4 // Эффективная фармакотерапия. – 2022. – Т. 18, № 6. – С. 20–30. DOI:10.33978/2307-3586-2022-18-6-20-30

18. Лазарева Н.Б. Ингибиторы дипептидилпептидазы-4: взгляд клинического фармаколога // Медицинский совет. – 2016. – № 19. – С. 114–121. DOI:10.21518/2079-701X-2016-19-114-121

19. Корбут А.И., Климонтов В.В. Терапия, основанная на инкретинах: почечные эффекты // Сахарный диабет. – 2016. – Т. 19, № 1. – C. 53–63. DOI:10.14341/DM7727

20. Gasbjerg L.S., Bergmann N.C., Stensen S., Christensen M.B., Rosenkilde M.M., Holst J.J., Nauck M., Knop F.K. Evaluation of the incretin effect in humans using GIP and GLP-1 receptor antagonists // Peptides. – 2020. – Vol. 125. – Art. ID: 170183. DOI:10.1016/j.peptides.2019.170183

21. Deacon C.F. Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus // Nat. Rev. Endocrinol. – 2020. – Vol. 16, No. 11. – P. 642–653. DOI:10.1038/s41574-020-0399-8

22. Kushwaha R.N., Haq W., Katti S.B. Discovery of 17 Gliptins in 17-Years of Research for the Treatment of Type 2 Diabetes: A Synthetic Overview // Chemistry & Biology Interface. – 2014. – Vol. 4. – P. 137–162.

23. Goldenberg R., Gantz I., Andryuk P.J., O’Neill E.A., Kaufman K.D., Lai E., Wang Y.N., Suryawanshi S., Engel S.S. Randomized clinical trial comparing the efficacy and safety of treatment with the once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or the once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin monotherapy // Diabetes Obes. Metab. – 2017. – Vol. 19, No. 3. – P. 394–400. DOI:10.1111/dom.12832

24. Stoimenis D., Karagiannis T., Katsoula A., Athanasiadou E., Kazakos K., Bekiari E., Matthews D.R., Tsapas A. Once-weekly dipeptidyl peptidase-4 inhibitors for type 2 diabetes: a systematic review and meta-analysis // Expert Opin. Pharmacother. – 2017. – Vol. 18, No. 9. – P. 843–851. DOI:10.1080/14656566.2017.1324848

25. Zou H., Zhu N., Li S. The emerging role of dipeptidyl-peptidase-4 as a therapeutic target in lung disease // Expert Opin. Ther. Targets. – 2020. – Vol. 24, No. 2. – P. 147–153. DOI:10.1080/14728222.2020.1721468

26. Anderluh M., Kocic G., Tomovic K., Kocic H., Smelcerovic A. DPP-4 inhibition: А novel therapeutic approach to the treatment of pulmonary hypertension? // Pharmacol. Ther. – 2019. – Vol. 201. – P. 1–7. DOI:10.1016/j.pharmthera.2019.05.007

27. Zhang S., Li P., Xin M., Jin X., Zhao L., Nan Y., Cheng X.W. Dipeptidyl peptidase-4 inhibition prevents lung injury in mice under chronic stress via the modulation of oxidative stress and inflammation // Exp. Anim. – 2021. – Vol. 70, No. 4. – P. 541–552. DOI:10.1538/expanim.21-0067

28. Patel P.M., Jones V.A., Kridin K., Amber K.T. The role of Dipeptidyl Peptidase-4 in cutaneous disease // Exp. Dermatol. – 2021. – Vol. 30, No. 3. – P. 304–318. DOI:10.1111/exd.14228

29. Tasic T., Bäumer W., Schmiedl A., Schwichtenhövel F., Pabst R., Raap U., von Hörsten S., Stephan M. Dipeptidyl peptidase IV (DPP4) deficiency increases Th1-driven allergic contact dermatitis // Clin. Exp. Allergy. – 2011. – Vol. 41, No. 8. – P. 1098–1107. DOI:10.1111/j.1365-2222.2011.03778.x

30. Kridin K., Bergman R. Association of Bullous Pemphigoid With Dipeptidyl-Peptidase 4 Inhibitors in Patients With Diabetes: Estimating the Risk of the New Agents and Characterizing the Patients // JAMA Dermatol. – 2018. – Vol. 154, No. 10. – P. 1152–1158. DOI:10.1001/jamadermatol.2018.2352

31. Huang J., Liu X., Wei Y., Li X., Gao S., Dong L., Rao X., Zhong J. Emerging Role of Dipeptidyl Peptidase-4 in Autoimmune Disease // Front Immunol. – 2022. – Vol. 13. – Art. ID: 830863. DOI:10.3389/fimmu.2022.830863

32. Guo Q., Zhang S., Huang J., Liu K. Alogliptin inhibits IL-1β-induced inflammatory response in fibroblast-like synoviocytes // Int. Immunopharmacol. – 2020. – Vol. 83. – Art. ID: 106372. DOI:10.1016/j.intimp.2020.106372

33. Han C.K., Lee W.F., Hsu C.J., Huang Y.L., Lin C.Y., Tsai C.H., Huang C.C., Fong Y.C., Wu M.H., Liu J.F., Tang C.H. DPP4 reduces proinflammatory cytokine production in human rheumatoid arthritis synovial fibroblasts // J. Cell Physiol. – 2021. – Vol. 236, No. 12. – P. 8060–8069. DOI:10.1002/jcp.30494

34. Jackson E.K. Context-dependent effects of dipeptidyl peptidase 4 inhibitors // Curr. Opin. Nephrol. Hypertens. – 2017. – Vol. 26, No.2. – P. 83–90. DOI:10.1097/MNH.0000000000000303

35. Gupta S., Sen U. More than just an enzyme: Dipeptidyl peptidase-4 (DPP-4) and its association with diabetic kidney remodelling // Pharmacol Res. – 2019. – Vol. 147. – P. 104391. DOI:10.1016/j.phrs.2019.104391

36. Allada R., Ren J., Restrepo R., Nistala R. Role of Dipeptidyl Peptidase 4 and Effects of a Western Diet in Renal Sodium Transport and Tubular Injury // FASEB. – 2022. – Vol. 36, No. S1. DOI:10.1096/fasebj.2022.36.s1.r5683

37. Min H.S., Kim J.E., Lee M.H., Song H.K., Kang Y.S., Lee M.J., Lee J.E., Kim H.W., Cha J.J., Chung Y.Y., Hyun Y.Y., Han J.Y., Cha D.R. Dipeptidyl peptidase IV inhibitor protects against renal interstitial fibrosis in a mouse model of ureteral obstruction // Lab. Invest. – 2014. – Vol. 94, No. 6. – P. 598–607. DOI:10.1038/labinvest.2014.50

38. O’Leary H., Ou X., Broxmeyer H.E. The role of dipeptidyl peptidase 4 in hematopoiesis and transplantation // Curr. Opin. Hematol. – 2013. – Vol. 20, No. 4. – P. 314–319. DOI:10.1097/MOH.0b013e32836125ac

39. Bae J.C. DPP-4 Inhibitor in Type 2 Diabetes Mellitus Patient with Non-Alcoholic Fatty Liver Disease: Achieving Two Goals at Once? // Endocrinol. Metab (Seoul). – 2022. – Vol. 37, No. 6. – P. 858–860. DOI:10.3803/EnM.2022.605

40. Jung E., Kim J., Kim C.S., Kim S.H., Cho M.H. Gemigliptin, a dipeptidyl peptidase-4 inhibitor, inhibits retinal pericyte injury in db/db mice and retinal neovascularization in mice with ischemic retinopathy // Biochim. Biophys. Acta. – 2015. – Vol. 1852, No. 12. – P. 2618–2629. DOI:10.1016/j.bbadis.2015.09.010

41. Avogaro A., Fadini G.P. The effects of dipeptidyl peptidase-4 inhibition on microvascular diabetes complications // Diabetes Care. – 2014. – Vol. 37, No. 10. – P. 2884–2894. DOI:10.2337/dc14-0865

42. Bazhin A.A., Chambon M., Vesin J., Bortoli J., Collins J.W., Turcatti G., Chou C.J., Goun E.A. A Universal Assay for Aminopeptidase Activity and Its Application for Dipeptidyl Peptidase-4 Drug Discovery // Anal. Chem. – 2019. – Vol. 91, No. 1. – P. 1098–1104. DOI:10.1021/acs.analchem.8b04672

43. Méndez L.R., Arrebola Y., Valdés-Tresanco M.E., Díaz-Guevara L., Bergado G., Sánchez B., Charli J.L., Pascual Alonso I. Bestatin and bacitracin inhibit porcine kidney cortex dipeptidyl peptidase IV activity and reduce human melanoma MeWo cell viability // Int. J. Biol. Macromol. – 2020. – Vol. 164. – P. 2944–2952. DOI:10.1016/j.ijbiomac.2020.08.157

44. Chittepu V.C.S.R., Kalhotra P., Osorio-Gallardo T., Jiménez-Martínez C., Torre R.R.R., Gallardo-Velazquez T., Osorio-Revilla G. New Molecular Insights into the Inhibition of Dipeptidyl Peptidase-4 by Natural Cyclic Peptide Oxytocin // Molecules. – 2019. – Vol. 24, No. 21. – Art. ID: 3887. DOI:10.3390/molecules24213887

45. Gao J., Gong H., Mao X. Dipeptidyl Peptidase-IV Inhibitory Activity and Related Molecular Mechanism of Bovine α-Lactalbumin-Derived Peptides // Molecules. – 2020. – Vol. 25, No. 13. – Art. ID: 3009. DOI:10.3390/molecules25133009

46. Huang P.K., Lin S.R., Chang C.H., Tsai M.J., Lee D.N., Weng C.F. Natural phenolic compounds potentiate hypoglycemia via inhibition of Dipeptidyl peptidase IV // Sci. Rep. – 2019. – Vol. 9, No. 1. – Art. ID: 15585. DOI:10.1038/s41598-019-52088-7

47. Wang J., Dai G., Li W. Berberine regulates glycemia via local inhibition of intestinal dipeptidyl peptidase-IV // Zhejiang Da Xue Xue Bao Yi Xue Ban. – 2016. – Vol. 45, No. 5. – P. 486–492. DOI:10.3785/j.issn.1008-9292.2016.09.06. Chinese

48. Kalhotra P., Chittepu V.C.S.R., Osorio-Revilla G., Gallardo-Velazquez T. Phytochemicals in Garlic Extract Inhibit Therapeutic Enzyme DPP-4 and Induce Skeletal Muscle Cell Proliferation: A Possible Mechanism of Action to Benefit the Treatment of Diabetes Mellitus // Biomolecules. – 2020. – Vol. 10, No. 2. – Art. ID: 305. DOI:10.3390/biom10020305

49. Narayanan N., Naik D., Sahoo J., Kamalanathan S. Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control // World J Virol. – 2022. – Vol. 11, No. 6. – P. 399–410. DOI:10.5501/wjv.v11.i6.399

50. Ортенберг Э.А., Суплотова Л.А. Ингибиторы дипептидилпептидазы-4: очевидное и вероятное (обзор литературы) // Медицинский совет. – 2022. – Т. 16, № 10. – С. 40–45. DOI:10.21518/2079-701X-2022-16-10-40-45

51. Vankadari N., Wilce J.A. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26 // Emerg. Microbes. Infect. – 2020. – Vol. 9, No. 1. – P. 601–604. DOI:10.1080/22221751.2020.1739565

52. Li Y., Zhang Z., Yang L., Lian X., Xie Y., Li S., Xin S., Cao P., Lu J. The MERS-CoV Receptor DPP4 as a Candidate Binding Target of the SARS-CoV-2 Spike // iScience. – 2020. – Vol. 23, No. 6. – Art. ID: 101160. DOI:10.1016/j.isci.2020.101160. Erratum in: iScience. – 2020. – Vol. 23, No. 8. – Art. ID: 101400.

53. Sebastián-Martín A., Sánchez B.G., Mora-Rodríguez J.M., Bort A., Díaz-Laviada I. Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology // Biomedicines. – 2022. – Vol. 10, No. 8. – Art. ID: 2026. DOI:10.3390/biomedicines10082026

54. Krejner-Bienias A., Grzela K., Grzela T. DPP4 Inhibitors and COVID-19-Holy Grail or Another Dead End? // Arch Immunol Ther Exp (Warsz). – 2021. – Vol. 69, No. 1. – P. 1. DOI:10.1007/s00005-020-00602-5

55. Dastan F., Abedini A., Shahabi S., Kiani A., Saffaei A., Zare A. Sitagliptin Repositioning in SARS-CoV-2: Effects on ACE-2, CD-26, and Inflammatory Cytokine Storms in the Lung // Iran J. Allergy Asthma Immunol. – 2020. – Vol. 19, No. S1. – P. 10–12. DOI:10.18502/ijaai.v19i(s1.r1).2849

56. Schlicht K., Rohmann N., Geisler C., Hollstein T., Knappe C., Hartmann K., Schwarz J., Tran F., Schunk D., Junker R., Bahmer T., Rosenstiel P., Schulte D., Türk K., Franke A., Schreiber S., Laudes M. Circulating levels of soluble Dipeptidylpeptidase-4 are reduced in human subjects hospitalized for severe COVID-19 infections // Int. J. Obes. (Lond). – 2020. – Vol. 44, No. 11. – P. 2335–2338. DOI:10.1038/s41366-020-00689-y. Erratum in: Int. J. Obes. (Lond). – 2022. – Vol. 46, No. 1. – Art. ID: 243.

57. Varin E.M., Mulvihill E.E., Beaudry J.L., Pujadas G., Fuchs S., Tanti J.F., Fazio S., Kaur K., Cao X., Baggio L.L., Matthews D., Campbell J.E., Drucker D.J. Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition // Cell Metab. – 2019. – Vol. 29, No. 2. – P. 320–334.e5. DOI:10.1016/j.cmet.2018.10.001

58. Kifle Z.D., Woldeyohanin A.E., Demeke C.A. SARS-CoV-2 and diabetes: A potential therapeutic effect of dipeptidyl peptidase 4 inhibitors in diabetic patients diagnosed with COVID-19 // Metabol. Open. – 2021. – Vol. 12. – Art. ID: 100134. DOI:10.1016/j.metop.2021.100134

59. Soare A., Györfi H.A., Matei A.E., Dees C., Rauber S., Wohlfahrt T., Chen C.W., Ludolph I., Horch R.E., Bäuerle T., von Hörsten S., Mihai C., Distler O., Ramming A., Schett G., Distler J.H.W. Dipeptidylpeptidase 4 as a Marker of Activated Fibroblasts and a Potential Target for the Treatment of Fibrosis in Systemic Sclerosis // Arthritis. Rheumatol. – 2020. – Vol. 72, No. 1. – P. 137–149. DOI:10.1002/art.41058

60. Herman G.A., Bergman A., Stevens C., Kotey P., Yi B., Zhao P., Dietrich B., Golor G., Schrodter A., Keymeulen B., Lasseter K.C., Kipnes M.S., Snyder K., Hilliard D., Tanen M., Cilissen C., De Smet M., de Lepeleire I., Van Dyck K., Wang A.Q., Zeng W., Davies M.J., Tanaka W., Holst J.J., Deacon C.F., Gottesdiener K.M., Wagner J.A. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes // J. Clin. Endocrinol. Metab. – 2006. – Vol. 91, No. 11. – P. 4612–4619. DOI:10.1210/jc.2006-1009

61. Hou L., Zhao T., Liu Y., Zhang Y. Efficacy and safety of sitagliptin compared with sulfonylurea therapy in patients with type 2 diabetes showing inadequately controlled glycosylated hemoglobin with metformin monotherapy: A meta-analysis // Exp. Ther. Med. – 2015. – Vol. 9, No. 4. – P. 1528–1536. DOI:10.3892/etm.2015.2277

62. Hayes J., Anderson R., Stephens J.W. Sitagliptin/metformin fixed-dose combination in type 2 diabetes mellitus: an evidence-based review of its place in therapy // Drug Des. Devel. Ther. – 2016. – Vol. 10. – P. 2263–2270. DOI:10.2147/DDDT.S93076

63. Fonseca V., Staels B., Morgan J.D. 2nd, Shentu Y., Golm G.T., Johnson-Levonas A.O., Kaufman K.D., Goldstein B.J., Steinberg H. Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized, placebo-controlled, 26-week trial in patients with type 2 diabetes // J. Diabetes Complications. – 2013. – Vol. 27, No. 2. – P. 177–183. DOI:10.1016/j.jdiacomp.2012.09.007

64. Шестакова М.В. Опыт применения ситаглиптина (первого ингибитора ДПП-4) в лечении сахарного диабета 2 типа в российской федерации: результаты наблюдательной программы «Диа-Да» // Сахарный диабет. – 2010. – Т. 13, № 3. – С. 57–60. DOI:10.14341/2072-0351-5489

65. Аметов А.С., Гусенбекова Д.Г. Роль ингибиторов ДПП-4 в коррекции нарушений жирового обмена у пациентов с СД 2 типа и ожирением // Сахарный диабет. – 2015. – Т. 18, № 3. – С. 85–92. DOI:10.14341/DM2015385-92

66. Павлова М.Г. Вилдаглиптин - новые возможности в терапии сахарного диабета 2 типа // Фарматека. – 2022. – Т. 29, № 11/12. – С. 36–40. DOI:10.18565/pharmateca.2022.11-12.36-40

67. Azuma K., Rádiková Z., Mancino J., Toledo F.G., Thomas E., Kangani C., Dalla Man C., Cobelli C., Holst J.J., Deacon C.F., He Y., Ligueros-Saylan M., Serra D., Foley J.E., Kelley D.E. Measurements of islet function and glucose metabolism with the dipeptidyl peptidase 4 inhibitor vildagliptin in patients with type 2 diabetes // J. Clin. Endocrinol. Metab. – 2008. – Vol. 93, No. 2. – P. 459–464. DOI:10.1210/jc.2007-1369

68. Odawara M., Sagara R. Effects of vildagliptin as add-on treatment in patients with type 2 diabetes mellitus: insights from long-term clinical studies in Japan // J. Diabetes Metab. Disord. – 2016. – Vol. 15. – Art. ID: 21. DOI:10.1186/s40200-016-0240-z

69. Аметов А.С. Галвус. 5 лет в России // Эндокринология. Новости. Мнения. Обучение. – 2014. – № 3 (8). – С. 10–16.

70. Kosaraju J., Murthy V., Khatwal R.B., Dubala A., Chinni S., Muthureddy Nataraj S.K., Basavan D. Vildagliptin: an anti-diabetes agent ameliorates cognitive deficits and pathology observed in streptozotocin-induced Alzheimer’s disease // J. Pharm. Pharmacol. – 2013. – Vol. 65, No. 12. – P. 1773–1784. DOI:10.1111/jphp.12148

71. Arruda-Junior D.F., Martins F.L., Dariolli R., Jensen L., Antonio E.L., Dos Santos L., Tucci P.J., Girardi A.C. Dipeptidyl Peptidase IV Inhibition Exerts Renoprotective Effects in Rats with Established Heart Failure // Front Physiol. – 2016. – Vol. 7. – Art. ID: 293. DOI:10.3389/fphys.2016.00293

72. O’Farrell A.M., van Vliet A., Abou Farha K., Cherrington J.M., Campbell D.A., Li X., Hanway D., Li J., Guler H.P. Pharmacokinetic and pharmacodynamic assessments of the dipeptidyl peptidase-4 inhibitor PHX1149: double-blind, placebo-controlled, single- and multiple-dose studies in healthy subjects // Clin. Ther. – 2007. – Vol. 29, No. 8. – P. 1692–1705. DOI:10.1016/j.clinthera.2007.08.005

73. Lotfy M., Singh J., Kalász H., Tekes K., Adeghate E. Medicinal Chemistry and Applications of Incretins and DPP-4 Inhibitors in the Treatment of Type 2 Diabetes Mellitus // Open Med. Chem. J. – 2011. – Vol. 5, No. 2. – P. 82–92. DOI:10.2174/1874104501105010082

74. Pattzi H.M., Pitale S., Alpizar M., Bennett C., O’Farrell A.M., Li J., Cherrington J.M., Guler H.P., PHX1149-PROT202 Study Group. Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12-week, double-blind, randomized, placebo-controlled, multicentre trial // Diabetes Obes. Metab. – 2010. – Vol. 12, No. 4. – P. 348–355. DOI:10.1111/j.1463-1326.2010.01195.x

75. Garcia-Soria G., Gonzalez-Galvez G., Argoud G.M., Gerstman M., Littlejohn T.W. 3rd, Schwartz S.L., O’Farrell A.M., Li X., Cherrington J.M., Bennett C., Guler H.P. The dipeptidyl peptidase-4 inhibitor PHX1149 improves blood glucose control in patients with type 2 diabetes mellitus // Diabetes Obes. Metab. – 2008. – Vol. 10, No. 4. – P. 293–300. DOI:10.1111/j.1463-1326.2008.00868.x

76. Schenk R., Nix D. TCT-180 Impact of the novel DPP-IV-inhibitor Dutogliptin in combination with G-CSF on survival rates and cardiac remodelling after acute myocardial infarction // J. Am. Coll. Cardiol. – 2016. – Vol. 68, Suppl. 18. – Art. ID: B74. DOI:10.1016/j.jacc.2016.09.322

77. Rosenstock J., Sankoh S., List J.F. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes // Diabetes Obes. Metab. – 2008. – Vol. 10, No. 5. – P. 376–386. DOI:10.1111/j.1463-1326.2008.00876.x

78. Matthaei S., Aggarwal N., Garcia-Hernandez P., Iqbal N., Chen H., Johnsson E., Chin A., Hansen L. One-year efficacy and safety of saxagliptin add-on in patients receiving dapagliflozin and metformin // Diabetes Obes. Metab. – 2016. – Vol. 18, No. 11. – P. 1128–1133. DOI:10.1111/dom.12741

79. Chacra A.R., Tan G.H., Apanovitch A., Ravichandran S., List J., Chen R.; CV181-040 Investigators. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial // Int. J. Clin. Pract. – 2009. – Vol. 63, No. 9. – P. 1395–1406. DOI:10.1111/j.1742-1241.2009.02143.x. Erratum in: Int. J. Clin. Pract. – 2010. – Vol. 64, No. 2. –Art. ID: 277.

80. Huang J., Jia Y., Sun S., Meng L. Adverse event profiles of dipeptidyl peptidase-4 inhibitors: data mining of the public version of the FDA adverse event reporting system // BMC Pharmacol. Toxicol. – 2020. – Vol. 21, No. 1. – Art. ID: 68. DOI:10.1186/s40360-020-00447-w

81. Петунина Н.А., Бращенкова А.В. Саксаглиптин в концепции эффективного управления сахарным диабетом 2 типа // Фарматека. – 2011. – № 16 (229). – С. 12–19.

82. Kosaraju J., Gali C.C., Khatwal R.B., Dubala A., Chinni S., Holsinger R.M., Madhunapantula V.S., Muthureddy Nataraj S.K., Basavan D. Saxagliptin: a dipeptidyl peptidase-4 inhibitor ameliorates streptozotocin induced Alzheimer’s disease // Neuropharmacology. – 2013. – Vol. 72. – P. 291–300. DOI:10.1016/j.neuropharm.2013.04.008

83. Verspohl E.J. Novel pharmacological approaches to the treatment of type 2 diabetes // Pharmacol. Rev. – 2012. – Vol. 64, No. 2. – P. 188–237. DOI:10.1124/pr.110.003319

84. Del Prato S., Barnett A.H., Huisman H., Neubacher D., Woerle H.J., Dugi K.A. Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial // Diabetes Obes Metab. – 2011. – Vol. 13, No. 3. – P. 258–267. DOI:10.1111/j.1463-1326.2010.01350.x

85. Taskinen M.R., Rosenstock J., Tamminen I., Kubiak R., Patel S., Dugi K.A., Woerle H.J. Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study // Diabetes Obes Metab. – 2011. – Vol. 13, No. 1. – P. 65–74. DOI:10.1111/j.1463-1326.2010.01326.x

86. Forst T, Uhlig-Laske B, Ring A, Graefe-Mody U., Friedrich C., Herbach K., Woerle H.J., Dugi K.A. Linagliptin (BI 1356), a potent and selective DPP-4 inhibitor, is safe and efficacious in combination with metformin in patients with inadequately controlled Type 2 diabetes // Diabet Med. – 2010. – Vol. 27, No. 12. – P. 1409–1419. DOI:10.1111/j.1464-5491.2010.03131.x

87. Owens D.R., Swallow R., Dugi K.A., Woerle H.J. Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study // Diabet. Med. 2011. – Vol. 28, No. 11. – P. 1352–1361. DOI:10.1111/j.1464-5491.2011.03387.x. Erratum in: Diabet. Med. – 2012. – Vol. 29, No. 1. – Art. ID: 158.

88. Gallwitz B., Rosenstock J., Rauch T., Bhattacharya S., Patel S., von Eynatten M., Dugi K.A., Woerle H.J. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial // Lancet. – 2012. – Vol. 380, No. 9840. – P. 475–483. DOI:10.1016/S0140-6736(12)60691-6

89. Gupta R., Walunj S.S., Tokala R.K., Parsa K.V., Singh S.K., Pal M. Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes // Curr. Drug. Targets. – 2009. – Vol. 10, No. 1. – P. 71–87. DOI:10.2174/138945009787122860

90. DeFronzo R.A., Fleck P.R., Wilson C.A., Mekki Q., Alogliptin Study 010 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study // Diabetes Care. – 2008. – Vol. 31, No. 12. – P. 2315–2317. DOI:10.2337/dc08-1035

91. Rosenstock J., Rendell M.S., Gross J.L., Fleck P.R., Wilson C.A., Mekki Q. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia // Diabetes Obes. Metab. – 2009. – Vol. 11, No. 12. – P. 1145–1152. DOI:10.1111/j.1463-1326.2009.01124.x

92. Chen X.W., He Z.X., Zhou Z.W., Yang T., Zhang X., Yang Y.X., Duan W., Zhou S.F. Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus // Clin. Exp. Pharmacol. Physiol. – 2015. – Vol. 42, No. 10. – P. 999–1024. DOI:10.1111/1440-1681.12455

93. Pratley R.E., Reusch J.E., Fleck P.R., Wilson C.A., Mekki Q. Alogliptin Study 009 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin added to pioglitazone in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study // Curr. Med. Res. Opin. – 2009. – Vol. 25, No. 10. – P. 2361–2371. DOI:10.1185/03007990903156111

94. Trujillo J.M., Wettergreen S.A., Nuffer W.A., Ellis S.L.,McDermott M.T. Cardiovascular Outcomes of New Medications for Type 2 Diabetes // Diabetes Technol. Ther. – 2016. – Vol. 18, No. 12. – P. 749–758. DOI:10.1089/dia.2016.0295

95. Мкртумян А.М. Алоглиптин – эффективный и безопасный ингибитор дипептидилпептидазы-4 в терапии больных сахарным диабетом 2 типа // Фарматека. – 2015. – № 5 (298). – С. 20–27.

96. Мкртумян А.М., Егшатян Л.В. Алоглиптин – высокоселективный ингибитор ДПП-4 с фокусом на кардиоваскулярную безопасность // Медицинский совет. – 2016. – № 5. – С. 104–107. DOI:10.21518/2079-701X-2016-05-104-107

97. Kim S.H., Jung E., Yoon M.K., Kwon O.H., Hwang D.M., Kim D.W., Kim J., Lee S.M., Yim H.J. Pharmacological profiles of gemigliptin (LC15-0444), a novel dipeptidyl peptidase-4 inhibitor, in vitro and in vivo // Eur. J. Pharmacol. – 2016. – Vol. 788. – P. 54–64. DOI:10.1016/j.ejphar.2016.06.016

98. Rhee E.J., Lee W.Y., Yoon K.H., Yoo S.J., Lee I.K., Baik S.H., Kim Y.K., Lee M.K., Park K.S., Park J.Y., Cha B.S., Lee H.W., Min K.W., Bae H.Y., Kim MJ, Kim J.A., Kim D.K., Kim S.W. A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15-0444 in patients with type 2 diabetes // Diabetes Obes. Metab. – 2010. – Vol. 12, No. 12. – P. 1113–1119. DOI:10.1111/j.1463-1326.2010.01303.x

99. Lim S., Han K.A., Yu J., Chamnan P., Kim E.S., Yoon K.H., Kwon S., Moon M.K., Lee K.W., Kim D.J., Kim M., Wongtanate M., Kim E.Y., Kim S.H., Lee M.K., INICOM Study Group. Efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes: A double-blind randomized controlled trial (INICOM study) // Diabetes Obes. Metab. – 2017. – Vol. 19, No. 1. – P. 87–97. DOI:10.1111/dom.12787

100. Maladkar M., Sankar S., Kamat K. Teneligliptin: heralding change in type 2 diabetes // J. Diabetes Mellitus. – 2016. – Vol. 6. – P. 113–131. DOI:10.4236/jdm.2016.62012

101. Kadowaki T., Kondo K. Efficacy, safety and dose-response relationship of teneligliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus // Diabetes Obes Metab. – 2013. – Vol. 15, No. 9. – P. 810–818. DOI:10.1111/dom.12092

102. Otsuki H., Kosaka T., Nakamura K., Shimomura F., Kuwahara Y., Tsukamoto T. Safety and efficacy of teneligliptin: a novel DPP-4 inhibitor for hemodialysis patients with type 2 diabetes // Int Urol Nephrol. – 2014. – Vol. 46, No. 2. – P. 427–432. DOI:10.1007/s11255-013-0552-6

103. Hashikata T., Yamaoka-Tojo M., Kakizaki R., Nemoto T., Fujiyoshi K., Namba S., Kitasato L., Hashimoto T., Kameda R., Maekawa E., Shimohama T., Tojo T., Ako J. Teneligliptin improves left ventricular diastolic function and endothelial function in patients with diabetes // Heart Vessels. – 2016. – Vol. 31, No. 8. – P. 1303–1310. DOI:10.1007/s00380-015-0724-7. Erratum in: Heart Vessels. – 2016. – Vol. 31, No. 8. – P. 1311–1312.

104. Kadowaki T., Kondo K. Efficacy and safety of teneligliptin added to glimepiride in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study with an open-label, long-term extension // Diabetes Obes. Metab. – 2014. – Vol. 16, No. 5. – P. 418–425. DOI:10.1111/dom.12235

105. Kadowaki T., Kondo K. Efficacy and safety of teneligliptin in combination with pioglitazone in Japanese patients with type 2 diabetes mellitus // J. Diabetes Investig. – 2013. – Vol. 4, No. 6. – P. 576–584. DOI:10.1111/jdi.12092

106. Kim M.K., Rhee E.J., Han K.A, Woo A.C., Lee M.K., Ku B.J., Chung C.H., Kim K.A., Lee H.W., Park I.B., Park J.Y., ChulJang H.C., Park K.S., Jang W.I., Cha B.Y. Efficacy and safety of teneligliptin, a dipeptidyl peptidase-4 inhibitor, combined with metformin in Korean patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled phase III trial // Diabetes Obes Metab. – 2015. – Vol. 17, No. 3. – P. 309–312. DOI:10.1111/dom.12424

107. Tanaka K., Okada Y., Mori H., Inada Y., Suzuka K., Uriu K., Tanaka Y. Efficacy of linagliptin and teneligliptin for glycemic control in type 2 diabetic patients with chronic kidney disease: assessment by continuous glucose monitoring; a pilot study // Diabetol. Int. – 2016. – Vol. 7, No. 4. – P. 368–374. DOI:10.1007/s13340-016-0258-y

108. Furuta S., Smart C., Hackett A., Benning R., Warrington S. Pharmacokinetics and metabolism of [14C]anagliptin, a novel dipeptidyl peptidase-4 inhibitor, in humans // Xenobiotica. – 2013. – Vol. 43, No. 5. – P. 432–442. DOI:10.3109/00498254.2012.731618

109. Kaku K. Dose-ranging study of anagliptin in Japanese patients with type 2 diabetes: a multi-centre, randomized, placebo-controlled, double-blind, parallel-group study // Jpn Pharmacol Ther. – 2012. – Vol. 40. – P. 973–984.

110. Yang H.K., Min K.W., Park S.W., Chung C.H., Park K.S., Choi S.H., Song K.H., Kim D.M., Lee M.K., Sung Y.A., Baik S.H., Kim I.J., Cha B.S., Park J.H., Ahn Y.B., Lee I.K., Yoo S.J., Kim J., Park Ie.B., Park T.S., Yoon K.H. A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes // Endocr. J. – 2015. – Vol. 62, No. 5. – P. 449–462. DOI:10.1507/endocrj.EJ14-0544

111. Kakuda H., Kobayashi J., Kakuda M., Yamakawa J., Takekoshi N. The effect of anagliptin treatment on glucose metabolism and lipid metabolism, and oxidative stress in fasting and postprandial states using a test meal in Japanese men with type 2 diabetes // Endocrine. – 2015. – Vol. 48, No. 3. – P. 1005–1009. DOI:10.1007/s12020-014-0376-x

112. Kaku K. Efficacy and safety of anagliptin add-on therapy in Japanese patients with type 2 diabetes // Jpn Pharmacol Ther. – 2012. – Vol. 40, No. 9. – P. 745–770.

113. Burness C.B. Omarigliptin: first global approval // Drugs. – 2015. – Vol. 75, No. 16. – P. 1947–1952. DOI:10.1007/s40265-015-0493-8

114. Sheu W.H., Gantz I., Chen M., Suryawanshi S., Mirza A., Goldstein B.J., Kaufman K.D., Engel S.S. Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes // Diabetes Care. – 2015. – Vol. 38, No. 11. – P. 2106–2114. DOI:10.2337/dc15-0109

115. Evans P.M., Bain S.C. Omarigliptin for the treatment of type 2 diabetes mellitus // Expert. Opin. Pharmacother. – 2016. – Vol. 17, No. 14. – P. 1947–1952. DOI:10.1080/14656566.2016.1218472

116. Tan X. Omarigliptin for the treatment of type 2 diabetes // Endocrine. – 2016. – Vol. 54, No. 1. – P. 24–31. DOI:10.1007/s12020-016-1011-9

117. Sharma R., Sun H., Piotrowski D.W, Ryder T.F., Doran S.D., Dai H., Prakash C. Metabolism, excretion, and pharmacokinetics of ((3,3-difluoropyrrolidin-1-yl)((2S,4S)-4-(4-(pyrimidin-2-yl)piperazin-1-yl)pyrrolidin-2-yl)methanone, a dipeptidyl peptidase inhibitor, in rat, dog and human // Drug Metab. Dispos. – 2012. – Vol. 40, No. 11. – P. 2143–2161. DOI:10.1124/dmd.112.047316

118. Muto C., Dai H., Teeter J.G., Johnson S., Cropp A.B., Chiba K., Suwa T. The pharmacokinetics and pharmacodynamics of PF-00734200, a DPP-IV inhibitor, in healthy Japanese subjects // Int J Clin Pharmacol Ther. – 2012. – Vol. 50, No. 7. – P. 505–509. DOI:10.5414/CP201614

119. Rosenstock J., Lewin A.J., Norwood P., Somayaji V., Nguyen T.T., Teeter J.G., Johnson S.L., Dai H., Terra S.G. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor PF-734200 added to metformin in Type 2 diabetes // Diabet. Med. – 2011. – Vol. 28, No. 4. – P. 464–469. DOI:10.1111/j.1464-5491.2010.03181.x

120. Terra S.G., Somayaji V., Schwartz S., Lewin A.J., Teeter J.G., Dai H., Nguyen T.T., Calle R.A. A Dose-Ranging Study of the DPP-IV Inhibitor PF-734200 Added to Metformin in Subjects With Type 2 Diabetes // Exp. Clin. Endocrinol. Diabetes. – 2011. – Vol. 119, No. 7. – P. 401–407. DOI:10.1055/s-0031-1273737

121. Галстян К.О., Недосугова Л.В., Петунина Н.А., Трахтенберг Ю.А., Востокова Н.В., Караваева О.В., Часовская Т.Е. Первый отечественный ингибитор ДПП-4 госоглиптин в сравнении с вилдаглиптином при лечении пациентов с сахарным диабетом 2 типа // Сахарный диабет. – 2016. – Т. 19, № 1. – С. 89–96. DOI:10.14341/DM7233

122. McKeage K. Trelagliptin: First Global Approval // Drugs. – 2015. – Vol. 75, No. 10. – P. 1161–1164. DOI:10.1007/s40265-015-0431-9

123. Grimshaw C.E., Jennings A., Kamran R., Ueno H., Nishigaki N., Kosaka T., Tani A., Sano H., Kinugawa Y., Koumura E., Shi L., Takeuchi K. Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism // PLoS One. 2016. – Vol. 11, No. 6. – Art. ID: e0157509. Published – 2016. DOI:10.1371/journal.pone.0157509

124. Inagaki N., Sano H., Seki Y., Kuroda S., Kaku K. Long-term safety and efficacy of a novel once-weekly oral trelagliptin as monotherapy or in combination with an existing oral antidiabetic drug in patients with type 2 diabetes mellitus: A 52-week open-label, phase 3 study // J. Diabetes Investig. – 2016. – Vol. 7, No. 5. – P. 718–726. DOI:10.1111/jdi.12499

125. Yong X., Hu T., Feng S., Du X., Shi H., Feng W. Synergism in Pharmacokinetics of Retagliptin and Metformin Observed during Clinical Trials of their Combination Therapy // Trop J. Pharm. Res. – 2015. – Vol. 14, No. 8. – P. 1481–1486. DOI:10.4314/tjpr.v14i8.22

126. Chae Y.N., Kim T.H., Kim M.K., Shin C.Y., Jung I.H., Sohn Y.S., Son M.H. Beneficial Effects of Evogliptin, a Novel Dipeptidyl Peptidase 4 Inhibitor, on Adiposity with Increased Ppargc1a in White Adipose Tissue in Obese Mice // PLoS One. – 2015. – Vol. 10, No. 12. – Art. ID: e0144064. DOI:10.1371/journal.pone.0144064

127. Cho J.M., Jang H.W., Cheon H., Jeong Y.T., Kim D.H., Lim Y.M., Choi S.H., Yang E.K., Shin C.Y., Son M.H., Kim S.H., Kim H.J., Lee M.S. A novel dipeptidyl peptidase IV inhibitor DA-1229 ameliorates streptozotocin-induced diabetes by increasing β-cell replication and neogenesis // Diabetes Res Clin Pract. – 2011. – Vol. 91, No. 1. – P. 72–79. DOI:10.1016/j.diabres.2010.10.012

128. Gu N., Park M.K., Kim T.E., Bahng M.Y., Lim K.S., Cho S.H., Yoon S.H., Cho J.Y., Jang I.J., Yu K.S. Multiple-dose pharmacokinetics and pharmacodynamics of evogliptin (DA-1229), a novel dipeptidyl peptidase IV inhibitor, in healthy volunteers // Drug Des. Devel. Ther. – 2014. – Vol. 8. – P. 1709–1721. DOI:10.2147/DDDT.S65678

129. Mattei P., Boehringer M., Di Giorgio P., Fischer H., Hennig M., Huwyler J., Koçer B., Kuhn B., Loeffler B.M., Macdonald A., Narquizian R., Rauber E., Sebokova E., Sprecher U. Discovery of carmegliptin: a potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes // Bioorg. Med. Chem. Lett. – 2010. – Vol. 20, No. 3. – P. 1109–1113. DOI:10.1016/j.bmcl.2009.12.024

130. Kuhlmann O., Carlile D., Noe J., Bentley D. Interaction potential of Carmegliptin with P-glycoprotein (Pgp) transporter in healthy volunteers // J. Drug Assess. –2014. – Vol. 3, No. 1. – P. 28–37. DOI:10.3109/21556660.2014.900065