Initial investigation of efficacy and safety of a new dipeptidyl peptidase-4 inhibitor, gosogliptin, for type 2 diabetes in Russia
Abstract
Current treatment strategies for type 2 diabetes mellitus (T2DM) are based on using safe and effective hypoglycaemic agents for preventing diabetic vascular complications and reducing the risks associated with weight gain and hypoglycaemia. These goals may be achieved using new agents with a fundamentally new mechanism of action: inhibitors of dipeptidyl peptidase-4 (DPP-4i). However, the wide distribution of this enzyme in the body is associated with extraglycaemic DPP-4i effects, both positive and negative. Thus, it is important to develop and implement new DPP-4i agents for clinical practice.
Aim.
To investigate the efficacy and safety of a novel DPP-4i, gosogliptin, for use as monotherapy and in combination with metformin vs. vildagliptin as monotherapy and in combination with metformin for patients with drug-naive type 2 diabetes in a multicentre, open, randomized clinical trial.
Materials and methods.
We enrolled 299 drug-naive type 2 diabetes patients; 149 patients were randomized to receive gosogliptin and 150 patients received tovildagliptin. These groups had similar baseline characteristics. After randomization, 12 weeks of monotherapy was administered to both groups. Further, it was decided to continue the monotherapy or in combination with metformin, depending on each patient. The results after the first 12 weeks are presented in this paper.
Results.
After 12 weeks of monotherapy, HbA1c levels decreased significantly from 8.61% to 7.41% (p <0.05) in the gosogliptin group and from 8.7% to 7.34% (p <0.05) in the vildagliptin group; these changes were not significantly different between these groups. Target HbA1c of ?7.0% was achieved for 59 patients (41%) who took gosogliptin and 66 patients (44%) who took vildagliptin (p=0.53). After 12 weeks of monotherapy, 11 episodes of mild hypoglycaemia occurred (7 on gosogliptin and 4 on vildagliptin), without clinical manifestations of blood glucose levels of <3.9 mmol/l based on metre readings. Only 14 adverse events (7 patients in each group) were assessed as ?related to? or ?probably related to? gosogliptin or vildagliptin.
Conclusion.
Our preliminary monotherapy study showed comparable efficacy and safety profiles for gosogliptin and vildagliptin.
Aim.
To investigate the efficacy and safety of a novel DPP-4i, gosogliptin, for use as monotherapy and in combination with metformin vs. vildagliptin as monotherapy and in combination with metformin for patients with drug-naive type 2 diabetes in a multicentre, open, randomized clinical trial.
Materials and methods.
We enrolled 299 drug-naive type 2 diabetes patients; 149 patients were randomized to receive gosogliptin and 150 patients received tovildagliptin. These groups had similar baseline characteristics. After randomization, 12 weeks of monotherapy was administered to both groups. Further, it was decided to continue the monotherapy or in combination with metformin, depending on each patient. The results after the first 12 weeks are presented in this paper.
Results.
After 12 weeks of monotherapy, HbA1c levels decreased significantly from 8.61% to 7.41% (p <0.05) in the gosogliptin group and from 8.7% to 7.34% (p <0.05) in the vildagliptin group; these changes were not significantly different between these groups. Target HbA1c of ?7.0% was achieved for 59 patients (41%) who took gosogliptin and 66 patients (44%) who took vildagliptin (p=0.53). After 12 weeks of monotherapy, 11 episodes of mild hypoglycaemia occurred (7 on gosogliptin and 4 on vildagliptin), without clinical manifestations of blood glucose levels of <3.9 mmol/l based on metre readings. Only 14 adverse events (7 patients in each group) were assessed as ?related to? or ?probably related to? gosogliptin or vildagliptin.
Conclusion.
Our preliminary monotherapy study showed comparable efficacy and safety profiles for gosogliptin and vildagliptin.
About the Authors
Lyudmila Viktorovna Nedosugova
I.M. Sechenov First Moscow State Medical University
Russian Federation
MD, PhD, Professor of the Endocrinology Chair of Postgraduate education institute
Competing Interests: The author declares the absence of funding for the preparation and review of the manuscript. The author is involved in a phase III study of the drug gosogliptin in the Research Center based at City Clinical Hospital № 67. The statistical data on the results of an interim analysis is provided by the company sponsoring the clinical trials LLC "SatRx"
Russian Federation
MD, PhD, Professor of the Endocrinology Chair of Postgraduate education institute
Competing Interests: The author declares the absence of funding for the preparation and review of the manuscript. The author is involved in a phase III study of the drug gosogliptin in the Research Center based at City Clinical Hospital № 67. The statistical data on the results of an interim analysis is provided by the company sponsoring the clinical trials LLC "SatRx"
Nina Alexandrovna Petunina
I.M. Sechenov First Moscow State Medical University
Russian Federation
MD, PhD, Professor, Head of the Endocrinology Chair of Postgraduate education institute
Competing Interests: The author declares the absence of funding for the preparation and review of the manuscript. The author is involved in a phase III study of the drug gosogliptin in the Research Center based at City Clinical Hospital № 67. The statistical data on the results of an interim analysis is provided by the company sponsoring the clinical trials LLC "SatRx"
Russian Federation
MD, PhD, Professor, Head of the Endocrinology Chair of Postgraduate education institute
Competing Interests: The author declares the absence of funding for the preparation and review of the manuscript. The author is involved in a phase III study of the drug gosogliptin in the Research Center based at City Clinical Hospital № 67. The statistical data on the results of an interim analysis is provided by the company sponsoring the clinical trials LLC "SatRx"
Karina Oganesovna Galstyan
I.M. Sechenov First Moscow State Medical University
Russian Federation
MD, PhD-student at the Endocrinology Chair of Postgraduate education institute
Competing Interests: The author declares the absence of funding for the preparation and review of the manuscript. The author is involved in a phase III study of the drug gosogliptin in the Research Center based at City Clinical Hospital № 67. The statistical data on the results of an interim analysis is provided by the company sponsoring the clinical trials LLC "SatRx"
Russian Federation
MD, PhD-student at the Endocrinology Chair of Postgraduate education institute
Competing Interests: The author declares the absence of funding for the preparation and review of the manuscript. The author is involved in a phase III study of the drug gosogliptin in the Research Center based at City Clinical Hospital № 67. The statistical data on the results of an interim analysis is provided by the company sponsoring the clinical trials LLC "SatRx"
References
1. Cунцов ЮИ. Современные сахароснижающие препараты, используемые в России при лечении сахарного диабета 2 типа. Сахарный диабет. 2012;1: 6-10. [Suntsov YI. Modern antihyperglycemic agents prescribed in Russia for type 2 diabetes mellitus. Diabetes mellitus. 2012;(1):6-9.] doi: 10.14341/2072-0351-5971
2. Mannucci E, Monami M, Lamanna C, Gori F, Marchionni N. Prevention of cardiovascular disease through glycemic control in type 2 diabetes: A meta-analysis of randomized clinical trials. Nutrition, Metabolism and Cardiovascular Diseases 2009;19(9):604-612. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0939475309000647 PubMed PMID: 19427768. doi: 10.1016/j.numecd.2009.03.021.
3. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. Под редакцией И.И. Дедова, М.В. Шестаковой (6-й выпуск). Сахарный диабет. 2013;(1s):1-121. Dedov I, Shestakova M, Aleksandrov A, Galstyan G, Grigoryan O, Esayan R, et al. Standards of specialized diabetes care. Edited by Dedov II, Shestakova MV (6th edition). Diabetes mellitus 2013;-(1S):1-120. doi: 10.14341/DM20131S1
4. Mentlein R, Heymann E, Scholz W, Feller AC, Flad H. Dipeptidyl peptidase IV as a new surface marker for a subpopulation of human T-lymphocytes. Cellular Immunology 1984;89(1):11-19. Available from: http://linkinghub.elsevier.com/retrieve/pii/0008874984901928 PubMed PMID: 6386188. doi: 10.1016/0008-8749(84)90192-8.
5. Zhаu Y, Yang L, Zhou Z. Dipeptidyl peptidase-4 inhibitors: Multitarget drugs, not only antidiabetes drugs. Journal of Diabetes 2014;6(1):21-29.
6. Mannucci E, Pala L, Ciani S, Bardini G, Pezzatini A, Sposato I, et al. Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus. Diabetologia 2005;48(6):1168-1172. Available from: http://www.diseaseinfosearch.org/result/2236 PubMed PMID: 15864535. doi: 10.1007/s00125-005-1749-8.
7. Pala L, Pezzatini A, Dicembrini I, Ciani S, Gelmini S, Vannelli BG, et al. Different modulation of dipeptidyl peptidase-4 activity between microvascular and macrovascular human endothelial cells. Acta Diabetol 2010;49(Suppl 1):59-59. Available from: http://www.nlm.nih.gov/medlineplus/diabetestype2.html PubMed PMID: 20455069. doi: 10.1007/s00592-010-0195-3.
8. Hafler DA, Fox DA, Manning ME, Schlossman SF, Reinherz EL, Weiner HL. In Vivo Activated T Lymphocytes in the Peripheral Blood and Cerebrospinal Fluid of Patients with Multiple Sclerosis. N Engl J Med 1985;312(22):1405-1411. Available from: http://www.nejm.org/doi/abs/10.1056/NEJM198505303122201 PubMed PMID: 2985995. doi: 10.1056/NEJM198505303122201.
9. Hildebrandt M, Rose M, Rüter J. Dipeptidyl Peptidase IV (DP IV, CD26) in Patients with Inflammatory Bowel Disease. Scand J Gastroenterol 2001;36(10):1067-1072. Available from: http://informahealthcare.com/doi/abs/10.1080/003655201750422675 PubMed PMID: 11589380. doi: 10.1080/003655201750422675.
10. Gotoh H, Hagihara M, Nagatsu T, Iwata H, Miura T. Activities of dipeptidyl peptidase II and dipeptidyl peptidase IV in synovial fluid from patients with rheumatoid arthritis and osteoarthritis. Clin Chem 1989;35(6):1016-1018. Available from: http://www.clinchem.org/cgi/pmidlookup?view=long&pmid=2567214 PubMed PMID: 2567214.
11. Christopherson 2nd KW, Hangoc G, Mantel CR, Broxmeyer HE. Modulation of hematopoietic stem cell homing and engraftment by CD26. Science 2004;305(5686):1000-1003. Available from: http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=15310902 PubMed PMID: 15310902. doi: 10.1126/science.1097071.
12. Wang Y, Hoffer BJ, Greig NH. DPP-4 Inhibitors for the Treatment of Parkinson's Disease. 2011. Available from: https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=1339
13. Ellis SL, Moser EG, Snell-Bergeon JK, Rodionova AS, Hazenfield RM, Garg SK. Effect of sitagliptin on glucose control in adult patients with Type 1 diabetes: a pilot, double-blind, randomized, crossover trial. Diabetic Medicine 2011;28(10):1176-1181. Available from: http://doi.wiley.com/10.1111/j.1464-5491.2011.03331.x PubMed PMID: 21923696. doi: 10.1111/j.1464-5491.2011.03331.x.
14. Li L, Shen J, Bala MM, Busse JW, Ebrahim S, Wong E, et al. Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies. BMJ 2014;348:2366. doi: 10.1136/bmj.g2366.
15. Karagiannis T, Paschos P, Paletas K, Matthews D, Tsapas A. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and metaanalysis. BMJ 2012;344:1366. doi: 10.1136/bmj.e1369
16. Karagiannis T, Boura P, Tsapas A. Safety of dipeptidyl peptidase 4 inhibitors: a perspective review. Ther Adv Drug 2014;5(3):138-146.
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For citations:
Nedosugova L.V., Petunina N.A., Galstyan K.O. Initial investigation of efficacy and safety of a new dipeptidyl peptidase-4 inhibitor, gosogliptin, for type 2 diabetes in Russia. Diabetes mellitus. 2014;17(4):81-86.
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