#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Promising molecules for treatment of hyperglycemia in patients with type 2 diabetes


Authors: Milan Kvapil
Authors‘ workplace: Interní klinika 2. LF UK a FN v Motole, Praha
Published in: Vnitř Lék 2016; 62(Suppl 4): 67-71
Category: Reviews

Overview

New antidiabetic drugs are being developed today that expand the range of pharmacological intervention, in particular for patients with type 2 diabetes (imeglimin, semaglutide, dulaglutide, FGF 21 analogue). At the same time innovations take place that “better” the well-proven molecules, they offer new application forms we have no experience of diabetology (osmotic pump for exenatide, faster acting insulin aspart). New properties are brought by just the change of concentration (insulin glargine in a concentration of 300 U/ml), unexpected positive results are also brought by new fixed-ratio combinations of antidiabetics (fixed-ratio combination of insulin degludec and liraglutide, fixed-ratio combination of insulin glargine and lixisenatide). Also results of clinical studies appear that concern molecules already in use which facilitate the formulation of new recommendations regarding treatment type 2 diabetes.

Key words:
type 2 diabetes mellitus – dulaglutide – FGF 21 – imeglimin – insulin aspart – insulin degludek – insulin glargine – ITCA 650 – liraglutide – national information diabetes system – semaglutide


Sources

1. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009; 58(4): 773–795. Dostupné z DOI: <http://dx.doi.org/10.2337/db09–9028>.

2. DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 1992; 15(3): 318–368.

3. DeFronzo RA. Pathogenesis of type 2 diabetes: implications for metformin. Drugs 1999; 58(Suppl 1): S29-S30.

4. Consoli A, Formoso G. Do thiazolidinediones still have a role in treatment of type 2 diabetes mellitus? Diabetes Obes Metab 2013; 15(11): 967–977. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12101>.

5. Pirags V, Lebovitz H, Fouqueray P. Imeglimin, a novel glimin oral antidiabetic, exhibits a good efficacy and safety profile in type 2 diabetic patients. Diabetes Obes Metab 2012; 14(9): 852–858. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1463–1326.2012.01611.x>.

6. Pacini G, Mari A, Fouqueray P et al. Imeglimin increases glucose-dependent insulin secretion and improves β-cell function in patients with type 2 diabetes. Diabetes Obes Metab 2015; 17(6): 541–545. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12452>.

7. Vial G, Chauvin MA, Bendridi N et al. Imeglimin normalizes glucose tolerance and insulin sensitivity and improves mitochondrial function in liver of a high-fat, high-sucrose diet mice model. Diabetes 2015; 64(6): 2254–2264. Dostupné z DOI: <http://dx.doi.org/10.2337/db14–1220>.

8. Fouqueray P, Bolze S, Pirags V et al. Dose-rating study to determine the optimum dose for imeglimin a novel treatment for type 2 diabetes. Diabetes 2015; 64(Suppl 1): 1169P. Dostupné z WWW: http://www.poxel.com/pdf/poster_Imeglimin-ADA-Poster-2015.pdf

9. Fouqueray P, Pirags V, Inzucchi SE et al. The efficacy and safety of imeglimin as add-on therapy in patiens with type 2 diabetes inadequately controlled with metformin monotherapy. Diabetes Care 2013; 36(3): 565–568. Dostupné z DOI: <http://dx.doi.org/10.2337/dc12–0453>.

10. Fouqueray P, Pirags V, Diamant M et al. The efficacy and safety of imeglimin as add-on therapy in patiens with type 2 diabetes inadequately controlled with sitagliptin monotherapy. Diabetes Care 2014; 37(7): 1924–1930. Dostupné z DOI: <http://dx.doi.org/10.2337/dc13–2349>.

11. Kvapil M. Imeglimin: o této molekule ještě uslyšíme. In: Kvapil M (ed.): Diabetologie 2016. Triton: Praha 2016: 139–142. ISBN 978–80–7553–031–8.

12. Glaesner W, Vick AM, Millican R et al. Engineering and characterization of the long-acting glucagonlike peptide-1 analogue LY2189265, an Fc fusion protein. Diabetes Metab Res Rev 2010; 26(4): 287–296. Dostupné z DOI: <http://dx.doi.org/10.1002/dmrr.1080>.

13. Barrington P, Chien JY, Showalter HD et al. A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analog, in patients with type 2 diabetes. Diabetes Obes Metab 2011; 13(5): 426–433. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1463–1326.2011.01364.x>.

14. Umpierrez G, Tofé Povedano S, Pérez Manghi F et al. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care 2014; 37(8): 2168–2176. Dostupné z DOI: <http://dx.doi.org/10.2337/dc13–2759>.

15. Nauck M, Weinstock RS, Umpierrez GE et al. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care 2014; 37(8): 2149–2158. Dostupné z DOI: <http://dx.doi.org/10.2337/dc13–2761>. Erratum in: Diabetes Care. 2015; 38(3): 538. Dostupné z DOI: <http://dx.doi.org/10.2337/dc15-er03>.

16. Weinstock RS, Guerci B, Umpierrez G et al. Safety and efficacy of once-weekly dulaglutide versus sitagliptin after 2 years in metformin-treated patients with type 2 diabetes (AWARD-5): a randomized, phase III study. Diabetes Obes Metab 2015; 17(9): 849–858. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12479>.

17. Dungan KM, Povedano ST, Forst T et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Lancet 2014; 384(9951): 1349–1357. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(14)60976–4>.

18. Nauck MA, Petrie JR, Sesti G. The once-weekly human GLP-1 analogue semaglutide provides significant reductions in HbA1c and body weight in patients with type 2 diabetes. Diabetologia 2012; 55(Suppl 1): S7.

19. Ahrén B, Comas LM, Kumar H et al. Efficacy and safety of once-weekly semaglutide vs sitagliptin as add-on to metformin and/or thiazolidinediones after 56 weeks in subjects with type 2 diabetes (SUSTAIN 2). Abstract number 185-OR. American Diabetes Association 76th Scientific Session, New Orleans, US; 10–14 June 2016.

20. Ahmann A, Capehorn M, Charpentier G et al. Efficacy and safety of once-weekly semaglutide vs exenatide ER after 56 weeks in subjects with type 2 diabetes (SUSTAIN 3). Abstract number 187-OR. American Diabetes Association 76th Scientific Session, New Orleans, US; 10–14 June 2016.

21. Nauck MA, Petrie JR, Sesti G et al. A phase 2, randomized, dose-finding study of the novel once-weekly human GLP-1 analog, semaglutide, compared with placebo and open-label liraglutide in patients with type 2 diabetes. Diabetes Care 2016; 39(2): 231–241. Dostupné z DOI: <http://dx.doi.org/10.2337/dc15–0165>.

22. Dostupné z WWW: <https://www.novonordisk.com/bin/getPDF.2007806>. [31. 8. 2016].

23. Dostupné z WWW: https://clinicaltrials.gov/ct2/results?term=semaglutide+oral&Search=Search [31. 8. 2016].

24. Dostálová I, Haluzíková D, Haluzík M. Fibroblast growth factor 21: a novel metabolic regulator with potential therapeutic properties in obesity/type 2 diabetes mellitus. Physiol Res 2009; 58(1): 1–7.

25. Iglesias P, Selgas R, Romero S et al. Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21. Eur J Endocrinol 2012; 167(3): 301–309. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-12–0357>.

26. Gaich G, Chien JY, Fu H et al. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab 2013; 18(3): 333–340. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cmet.2013.08.005>.

27. Rohloff CM, Alessi TR, Yang B et al. DUROS technology delivers peptides and proteins at consistent rate continuously for 3 to 12 months. J Diabetes Sci Technol 2008; 2(3): 461–467.

28. Henry RR, Logan D, Alessi T et al. A randomized, open-label, multicenter, 4-week study to evaluate the tolerability and pharmacokinetics of ITCA 650 in patients with type 2 diabetes. Clin Ther 2013; 35(5): 634–645.e1. Dostupné z DOI: <http://dx.doi.org/10.1016/j.clinthera.2013.03.011>.

29. Henry RR, Rosenstock J, Logan DK et al. Randomized trial of continuous subcutaneous delivery of exenatide by ITCA 650 versus twice-daily exenatide injections in metformin-treated type 2 diabetes. Diabetes Care 2013; 36(9): 2559–2565. Dostupné z DOI: <http://dx.doi.org/10.2337/dc12–2410>. Erratum in Diabetes Care 2014; 37(1): 312.

30. Morrow L, Muchmore DB, Hompesch M et al. Comparative pharmacokinetics and insulin action for three rapid-acting insulin analogs injected subcutaneously with and without hyaluronidase. Diabetes Care 2013; 36(2): 273–275. Dostupné z DOI: <http://dx.doi.org/10.2337/dc12–0808>.

31. Heise T, Hövelmann U, Brøndsted L et al. Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart. Diabetes Obes Metab 2015; 17(7): 682–688. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12468>.

32. Becker RH, Nowotny I, Teichert L et al. Low within- and between-day variability in exposure to new insulin glargine 300 U/ml. Diabetes Obes Metab 2015; 17(3): 261–267. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12416>.

33. Riddle MC, Yki-Järvinen H, Bolli GB et al. One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension. Diabetes Obes Metab 2015; 17(9): 835–842. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12472>.

34. Steinstraesser A, Schmidt R, Bergmann K et al. Investigational new insulin glargine 300 U/ml has the same metabolism as insulin glargine 100 U/ml. Diabetes Obes Metab 2014; 16(9): 873–876. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12283>.

35. Janíčková-Žďarská D, Piťhová P, Pavlík T et al. The PROROK project results after 6 months of intervention (Prospective observation project focusing on the relevance of the difference between fasting blood glucose levels and postprandial blood glucose for estimation of success of type 2 diabetes therapy). Vnitř Lék 2015; 61(11 Suppl 3): 3S44–3S49.

36. Gough SC, Bode B, Woo V et al. [NN9068–3697 (DUAL-I) trial investigators]. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabetes Endocrinol 2014; 2(11): 885–893. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(14)70174–3>.

37. Gough SC, Bode BW, Woo VC et al. One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial. Diabetes Obes Metab 2015; 17(10): 965–973. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.12498>.

38. Lingvay I, Manghi FP, García-Hernández P et al. [DUAL V Investigators]. Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients With Uncontrolled Type 2 Diabetes: The DUAL V Randomized Clinical Trial. JAMA 2016; 315(9): 898–907. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2016.1252>.

39. Kvapil M. Realistic possibilities of using data sources in quality assessment of care of patients with diabetes in the Czech Republic: National Diabetes Information System. Vnitř Lék 2015; 61(11 Suppl 3): 3S10–3S13.

40. Dušek L. The National Health Care Information System of the Czech Republic will significantly enhance the information support of diabetology. Vnitř Lék 2015; 61(11 Suppl 3): 3S8–3S9.

41. Kvapil M. The population of patients with diabetes has changed, the patients live longer and are at greater risk of heart failure. Vnitř Lék 2016; 62(4): 246–247.

Labels
Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue Suppl 4

2016 Issue Suppl 4

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#