Diabetes Mellitus Tip 2’de İnkretin Temelli Tedaviler

Diyabet tedavisinde, geleneksel yöntemlerle kür sağlanamamaktadır. Diyabetin salgın derecesinde artışı patofizyolojsinin daha iyi anlaşılmasını sağlayacak araştırmalarla birlikte yeni tedavilerin geliştirilmesini zorunlu kılmaktadır. Metformin tedavisine cevap vermeyen durumlarda tercih edilen ilaçlar; hipoglisemi, kilo alımı ve istenmeyen kardiak olaylara neden olabilmektedirler. Günümüzde etkin glukoz ve kilo kontrolü sağlayan inkretin bazlı tedaviler geliştirilmiştir. İnkretinler pankreasta glukoza bağımlı insülin sekresyonunu artırırken, glukagon sekresyonunu baskılar.Glukagon benzeri peptid-1 reseptör agonistleri ve dipeptidil peptidaz-4 inhibitörleri inkretin bazlı tedavilerdir. Glukagon benzeri peptid-1 reseptör agonistleri önemli tedavilerden olup, monoterapi veya kombine tedavilerle birlikte kullanılabilmektedir. İyi glisemik kontrol sağlamalarının yanında hipoglisemi oranların düşük olması ve kilo kaybına neden olmaları önemli avantajlarıdır. Dipeptidil peptidaz-4 inhibitörleri; glukagon benzeri peptid-1 ve glukoz ba- ğımlı insülinotropik polipeptid gibi inkretin hormonların hızlıca inaktivasyonuna neden olur. DPP-4 inhibitörleri; dolaşımdaki inkretin hormonların yıkım

Incretin Based Therapies in Type 2 Diabetes Mellitus

For the treatment of T2DM; cure can not be achieved with conventional methods. The degree of increase in the epidemic of diabetes; together with the research of new treatments will provide a better understanding of patophysiology necessitates the development. Preferred drugs in cases that do not respond to metformin; hypoglycemia, can cause weight gain and are undesirable cardiac event. Today; incretin-based therapies have been developed that provide effective glucose level and weight control. Incretins while increasing glucose dependent insulin secretion in the pancreas, suppress glucagon secretion. Glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors, are incretin based treatment. Glucagon-like peptide-1 receptor agonists is the most important treatment can be used with monotherapy or combination therapy. Glucagon-like peptide-1 agonists, besides providing good glycemic control, the low rate of hypoglycemia and weight loss are causing significant advantage. Dipeptidyl peptidase-4 inhibitors; leads to rapid inactivation of incretin hormones such as glucagon-like peptide-1 agonists and glucose dependent insulinotropic polypeptide. Dipeptidyl peptidase-4 inhibitors; they extend the duration of action of glucagon-like peptide-1 by inhibiting the degradation of incretin hormones in circulation

___

  • 1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047–53.
  • 2. Stonehouse AH, Darsow T, Maggs DG. Incretin-based therapies. J Diabetes 2012;4:55–67.
  • 3. McIntosh CH, Demuth HU, Pospisilik JA, Pederson R. Dipeptidyl peptidase IV inhibitors: how do they work as new antidiabetic agents? Regul Pept 2005;128:159–65.
  • 4. Creutzfeldt W. The incretin concept today. Diabetol 1979;16:75–85.
  • 5. Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 1986;63:492–8.
  • 6. Holst JJ. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture. Diabetol 2006;49:253–60.
  • 7. Eissele R, Göke R, Willemer S, Harthus HP, Vermeer H, Arnold R, et al. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 1992;22:283–91.
  • 8. Deacon CF, Pridal L, Klarskov L, Olesen M, Holst JJ. Glucagonlike peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig. Am J Physiol 1996;271:458–64.
  • 9. Vilsboll T, Agersø H, Krarup T, Holst JJ. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J Clin Endocrinol Metab 2003;88:220–4.
  • 10. Deacon CF, Nauck MA, Meier J, Hücking K, Holst JJ. Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide. J Clin Endocrinol Metab 2000;85:3575–81.
  • 11. Vilsboll T, Agersø H, Lauritsen T, Deacon CF, Aaboe K, Madsbad S, et al. The elimination rates of intact GIP as well as its primary metabolite, GIP 3–42, are similar in type 2 diabetic patients and healthy subjects. Regul Pept 2006;137:168–72.
  • 12. Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagonlike peptide-1 by human plasma in vitro yields an Nterminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab 1995;80:952–7.
  • 13. Deacon CF, Nauck MA, Toft-Nielsen M, Pridal L, Willms B, Holst JJ. Both subcutaneously and intravenously administered glucagon-like peptide I are rapidly degraded from the NH2- terminus in type II diabetic patients and in healthy subjects. Diabetes 1995;44:1126–31.
  • 14. Holst JJ, Deacon CF. Inhibition of the activity of dipeptidylpeptidase IV as a treatment for type 2 diabetes. Diabetes 1998;47:1663–70.
  • 15. Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J, Marks V. Glucagon-like peptide-1(7–36)amide and glucosedependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. J Endocrinol 1993;138:159–66.
  • 16. Orskov C, Wettergren A, Holst JJ. Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand J Gastroenterol 1996;31:665–70.
  • 17. Ahren B, Carr RD, Deacon CF. Incretin hormone secretion over the day. Vitam Horm 2010;84:203–20.
  • 18. Deacon CF. What do we know about the secretion and degradation of incretin hormones? Regul Pept 2005;128:117–24.
  • 19. Lindgren O, Mari A, Deacon CF, Carr RD, Winzell MS, Vikman J, et al. Differential islet and incretin hormone responses in morning versus afternoon after standardized meal in healthy men. J Clin Endocrinol Metab 2009;94:2887–92.
  • 20. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterol 2007;132:2131–57.
  • 21. Schirra J, Nicolaus M, Roggel R, Katschinski M, Storr M, Woerle HJ, et al. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antropyloro-duodenal motility in humans. Gut 2006;55:243–51
  • 22. Nauck MA, Niedereichholz U, Ettler R, Holst JJ, Orskov C, Ritzel R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol 1997;273:981–8.
  • 23. Verdich C, Flint A, Gutzwiller JP, Näslund E, Beglinger C, Hellström PM, et al. A meta-analysis of the effect of glucagonlike peptide-1(7–36)amide on ad libitum energy intake in humans. J Clin Endocrinol Metab 2001;86:4382–9.
  • 24. Madsbad S, Krarup T, Deacon CF, Holst JJ. Glucagon- like peptide receptor agonists and dipeptidyl peptidase-4 inhibitors in the treatment of diabetes: a review of clinical trials. Curr Opin Clin Nutr Metab Care 2008;11:491–9.
  • 25. Muscelli E, Mari A, Casolaro A, Camastra S, Seghieri G, Gastaldelli A, et al. Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients. Diabetes 2008;57:1340–8.
  • 26. Knop FK, Aaboe K, Vilsboll T, Volund A, Madsbad S, Holst JJ, et al. Reduced incretin effect in obese subjects with normal glucose tolerance as compared to lean control subjects. Diabetes 2008;57:410.
  • 27. Carr RD, Larsen MO, Jelic K, Lindgren O, Vikman J, Holst JJ, et al. Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, nondiabetic men. J Clin Endocrinol Metab 2010;95:872–8.
  • 28. Toft-Nielsen MB, Damholt MB, Madsbad S, Hilsted LM, Hughes TE, Michelsen BK, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab 2001;86:3717–23.
  • 29. Vollmer K, Holst JJ, Baller B, Ellrichmann M, Nauck MA, Schmidt WE, et al. Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 2008;57:678–87.
  • 30. Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2(non-insulin-dependent) diabetes. Diabetol 1986;29:46–52.
  • 31. Bagger JI, Knop FK, Lund A, Vestergaard H, Holst JJ, Vilsbøll T. Impaired regulation of the incretin effect in patients with type 2 diabetes. J Clin Endocrinol Metab 2011;96:737–45.
  • 32. Chiniwala N, Jabbour S. Management of diabetes mellitus in the elderly. Curr Opin Endocrinol Diabetes Obes 2011:18:148–52. 33. Rodbard HW, Jellinger PS, Davidson JA, Einhorn D, Garber AJ, Grunberger G, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract 2009;15:540–59.
  • 34. Ghatak SB, Patel DS, Shanker N, Srivstava A, Deshpande SS, Panchal SJ. Alogliptin: a novel molecule for improving glycemic control in type II diabetes mellitus. Curr Diabetes Rev 2010;6:410–21.
  • 35. Hollander PA, Kushner P. Type 2 diabetes comorbidities and treatment challenges: rationale for DPP-4 inhibitors. Postgrad Med 2010;122:71–80.36. Bock G, Dalla Man C, Micheletto F, Basu R, Giesler PD, Laugen J, et al. The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose. Clin Endocrinol (Oxf ) 2010;73:189–96.
  • 37. Tibaldi J. Importance of postprandial glucose levels as a target for glycemic control in type 2 diabetes. South Med J 2009;102:60–6.
  • 38. Januvia™(sitagliptin) tablets [package insert]. Whitehouse Station, NJ. Merck and Co Inc; 2012.
  • 39. Tradjenta™(linagliptin) tablets [package insert]. Ridgefield, CT. Boehringer Ingelheim Pharmaceuticals Inc; 2011.
  • 40. Pattzi HM, Pitale S, Alpizar M, Bennett C, O’Farrell AM, Li J, et al. 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;12:348–55.
  • 41. Drucker D, Buse J, Taylor K, Kendall DM, Trautmann M, Zhuang D, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, noninferiority study. Lancet 2008;372:1240–50.
  • 42. Buse J, Nauck M, Forst T, Sheu WH, Shenouda SK, Heilmann CR, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet 2013;381:117–24.
  • 43. Rosenstock J, Raccah D, Koranyi L, Maffei L, Boka G, Miossec P, et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X). Diabetes Care 2013;36:2945–51.
  • 44. Pratley R, Nauck M, Barnett A, Feinglos MN, Ovalle F, Harman-Boehm I, et al. Once weekly albiglutide versus oncedaily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, openlabel, multicentre, non-inferiority phase 3 study. Lancet Diabetes Endocrinol 2014;2:289–97.
  • 45. Wysham C, Blevins T, Arakaki R, Colon G, Garcia P, Atisso C, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care 2014;37:2159–67.
  • 46. Buse J, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallelgroup, multinational, open-label trial (LEAD-6). Lancet 2009;374:39–47.
  • 47. Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab 2011;96:1301–10.
  • 48. Göke R, Fehmann HC, Linn T, Schmidt H, Krause M, Eng J, et al. Exendin-4 is a high potency agonist and truncated exendin- (9–39)-amide an antagonist at the glucagon-like peptide 1-(7–36)-amide receptor of insulin-secreting beta-cells. J Biol Chem 1993;268:19650–5.
  • 49. Amylin Pharmaceuticals. Bydureon PI. http:/documents. bydureon. com/Bydureon_PI. pdf Accessed May 2013.
  • 50. Agersø H, Jensen LB, Elbrønd B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetol 2002;45:195–202.
  • 51. Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W et al. Pharmacokinetics and pharmacodynamiceffects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol 2006;46:876–86.
  • 52. He YL, Serra D, Wang Y, Campestrini J, Riviere GJ, Deacon CF, et al. Pharmacokinetics and pharmacodynamics of vildagliptin in patients with type 2 diabetes mellitus. Clin Pharmacokinet 2007;46:577–88.
  • 53. DeYoung MB, MacConell L, Sarin V, Trautmann M, Herbert P. Encapsulation of exenatide in poly-(D, L-lactide-co-glycolide) microspheres produced an investigational long-acting onceweekly formulation for type 2 diabetes. Diabetes Technol Ther 2011;13:1145–54.
  • 54. Sanofi-aventis. Lixisenatide SPC. Lixisenatide summary of product characteristics. http://ec.europa.eu/health/documents/ community-register. Accessed May 2013.
  • 55. Knudsen LB, Nielsen PF, Huusfeldt PO, Johansen NL, Madsen K, Pedersen FZ, et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once Daily administration. J Med Chem 2000;43:1664–9.
  • 56. Gerich J. DPP-4 inhibitors: what may be the clinical differentiators? Diabetes Res Clin Pract 2012;90:131–40. 57. Davidson J. Advances in therapy for type 2 diabetes: GLP-1 receptor agonists and DPP-4 inhibitors. Cleve Clin J Med 2009;76:28–38.
  • 58. Madsbad S. Exenatide and liraglutide: different approaches to develop GLP-1 receptor agonists (incretin mimetics)- preclinical and clinical results. Best Pract Res Clin Endocrinol Metab 2009;23:463–77.
  • 59. Bolli G, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Wu Y, et al. Efficacy and safety of lixisenatide once-daily versus placebo in patients with type 2 diabetes mellitus insufficiently controlled on met- formin (GetGoal-F1)Abstract]. Diabetologia 2011;54:316–7.
  • 60. Novo Nordisk. Victoza PI. http://www.novo-pi. com/victoza.pdf Accessed May 2013.
  • 61. Merck Sharp & Dohme Corp. Januvia SPC. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_Product_ Information/human/000722/WC500039054.pdf AccessedMay 2013.
  • 62. Bristol-Myers Squibb. Onglyza SPC. http://www.ema.europa.eu/ docs/en_GB/document_library/EPAR_-_Product_Information/ human/001039/WC500044316.pdf Accessed May 2013.
  • 63. Novartis Galvus SPC. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/ human/000771/WC5000020327.pdf Accessed May 2013.
  • 64. Boehringer Ingelheim Pharmaceuticals,Inc. Trajenta SPC. http:// www.ema.europa.eu /docs/en_GB/document_library/EPAR_ Product_Information/human/002110/WC5001155745.pdf Accessed May 2013.
  • 65. Nakatani K, Kurose T, Hyo T, Watanabe K, Yabe D, Kawamoto T, et al. Drug-induced generalized skin eruption in a diabetes mellitus patient receiving a dipeptidyl peptidase-4 inhibitor plus metformin. Diabetes Ther 2012;3:14.
  • 66. Nauck MA. A critical analysis of the clinical use of incretinbased therapies: the benefits by far outweigh the potential risks. Diabetes Care 2013;36:2126–32.
  • 67. Noel RA, Braun DK, Patterson RE, Bloomgren GL. Increased risk of acute pancreatitis observed in patients with type 2 diabetes. Diabetes Care 2009;32:834–8.
  • 68. Houlden R, Ross S, Harris S, Yale JF, Sauriol L, Gerstein HC. Treatment satisfaction and quality of life using an early insulinization strategy with insulin glargine compared to an adjusted oral therapy in the management of type 2 diabetes: the Canadian INSIGHT Study. Diabetes Res Clin Pract 2007;78:254–8.
  • 69. Pratley R, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, et al. One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial. Int J Clin Pract 2011;65:397–407.
  • 70. Gerich J. Pathogenesis and management of postprandial hyperglycemia: role of incretin-based therapies. Int J Gen Med 2013;6:877–95.
  • 71. Stonehouse A, Walsh B, Cuddihy R. Exenatide once-weekly clinical development: safety and efficacy across a range of background therapies. Diabetes Technol Ther 2011;13:1063–9.
  • 72. Amylin Pharmaceuticals. Byetta PI. http://documents.byetta. com/Byetta_PI.pdf Accessed May 2013.
  • 73. Lopez-Ruiz A, del Peso-Gilsanz C, Meoro-Aviles A, Palao JS, Andreu A, Cabezuelo J, et al. Acute renal failure when exenatide is co-administered with diuretics and angiotensin II blockers. Pharm World Sci 2010;32:559–61.
  • 74. Kaakeh Y, Kanjee S, Boone K, Sutton J. Liraglutide- induced acute kidney injury. Pharmacotherapy 2012;32:7–11.
  • 75. Nandakoban H, Furlong TJ, Flack JR. Acute tubulointerstitial nephritis following treatment with exenatide. Diabet Med 2013;30:123–5.
  • 76. Weise WJ, Sivanandy MS, Block CA, Comi RJ. Exenatideassociated ischemic renal failure. Diabetes Care 2009;32:22–3.
  • 77. Kuehn B. Exenatide and kidney function. JAMA 2009;302:2644.
  • 78. Leibovitz E, Gottlieb S, Goldenberg I, Gevrielov-Yusim N, Matetzky S, Gavish D. Sitagliptin pretreatment in diabetes patients presenting with acute coronary syndrome: results from the Acute Coronary Syndrome Israeli Survey (ACSIS). Cardiovasc Diabetol 2013;12:53.
  • 79. Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev 2012;33:187–215.
  • 80. Garber AJ. Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability. Diabetes Care 2011;34:279–84.
  • 81. Dicker D. DPP-4 inhibitors: impact on glycemic control and cardiovascular risk factors. Diabetes Care 2011;34:276–8.
Kafkas Journal of Medical Sciences-Cover
  • ISSN: 2146-2631
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2011
  • Yayıncı: Kafkas Üniversitesi
Sayıdaki Diğer Makaleler

Osteolitik Benign Kalvarial Kitlelere Radyolojik Yaklaşım

Rasim YANMAZ, Hanifi BAYAROĞULLARI

Yatarak Tedavi Gören Psikiyatri Hastalarında Beden Dismorfik Bozukluğu Yaygınlığı ve Özellikleri: Edirne/TÜRKİYE’de Kesitsel Bir Araştırma

Yasin TAŞDELEN, Yüksel KIVRAK, Mehmet AŞOĞLU, Rugül KÖSE ÇINAR, Ercan ABAY

Platelet Lenfosit Oranı ve Akut Apandisit

Şahin KAHRAMANCA, Gülay ÖZGEHAN, Oskay KAYA, Tevfik Hadi KÜÇÜKPINAR, Hülagü KARGICI, Mehmet Fatih AVŞAR

İçme Sularındaki Mikro Element Düzeylerinin Adölesan Vücut Kompozisyonlarına Etkisi

İhsan ÇETİN, Aydan NAZİK, Mahmut Tahir NALBANTÇILAR, Kezban TOSUN

Pelvik Organ Prolapsuslu Olgularda Semptomatoloji

Yakup BAYKUŞ, Rulin DENİZ, Ebru ÇELİK KAVAK

Non Q, Non ST Elevasyonlu Myokard Enfarktüslü ve Stabil Olmayan Anjina Pektorisli (USAP) Hastalarda Miyokard Performans İndeksi (MPİ) ile C-reaktive Protein (CRP) ve Ortalama Trombosit Hacmi (MPV) Arasındaki İlişkinin İncelenmesi

Eray ATALAY, Mehmet Burak AKTUĞLU, Mustafa VELET

Lomber Disk Hernili Hastalarda Perkütan Lazer Disk Dekompresyonunun Etkinliği

Mustafa Kemal İLİK

Adıyaman Üniversitesi Nöroloji Kliniğinde Botulinum Toksin Uygulamaları: Retrospektif Bir Çalışma

Yaşar ALTUN

Behçet Hastalığı Olan Gebede Anestezi Yönetimi

Erdinç KOCA, Hasan ŞAYAN

Tunika Vajinalis Metastazı ile Prezante Olan Okkult Hepatoid Tip Mide Kanseri: Olgu Sunumu

Yavuz METİN, Nurgül ORHAN METİN, Oğuzhan ÖZDEMİR, Hakkı UZUN, Recep BEDİR