Clinical and laboratory characteristics of exenatide-given patients in endocrinology clinic of a university hospital

Amaç: Eksenatid, GLP-1 reseptörlerine yüksek afinitede bağlanmakta ve endojen GLP-1 etkisi olan glikoz bağımlı insülin sekresyonu, gastrik boşalmanın geciktirilmesi, glukagon süpresyonu, iştah baskılanması ve β-hücre kitlesini artırıcı etkilerini göstermektedir. Tip 2 diyabet tedavisinde metformin ve sulfonilüre veya her ikisinin beraber kullanılmasıyla glisemik kontrol sağlanamayan özellikle obez hastalarda kullanılmaktadır. İyi glisemik kontrol ve kilo kaybı sağlaması nedeniyle kan şekerleri yüksek seyreden oral antidiyabetik tedavinin yetersiz kaldığı vakalarda insülin tedavisine eklenmiştir. Çalışmamızda; kliniğimizde en az 4 ay ve daha fazla süreyle eksenatid tedavisi alan hastaların biyokimyasal ve klinik parametrelerini paylaşmayı planladık. Yöntemler: Çalışmaya Temmuz 2011 ile Aralık 2013 tarihleri arasında eksenatid başlanan ve en az 4 (ort: 7,3) ay takipleri tamamlanan 26 (2 erkek, 24 kadın) hasta alındı. Hastaların hepsi tedavi öncesi metformin yanında kombine oral antidiyabetik tedavi altında iken, 6 hasta metformin tedavisine ek olarak insülin tedavisi almaktaydı. Bulgular: Çalışmaya alınan hastalarda tedavi sonrası Hemoglobin A1c düzeylerinde kadınlarda %0.98, erkeklerde % 1.4, vücut ağırlığında (kg) kadınlarda % 0.64, erkeklerde % 0.57, beden kitle indeksi ölçümlerinde kadınlarda % 0.61, erkeklerde % 0.56 düşme gözlendi. Sonuç: İnsülin, metformin veya oral antidiyabetik tedaviyi kombine veya tek başına alan obez hastalarda tedaviye eksenatide eklenmesi ile hastalarda kilo kaybı ve Hemoglobin A1c düzeylerinde düşme tespit edilmiştir.

Anahtar Kelimeler:

Eksenatid, GLP-1, Diabetes mellitus

Clinical and laboratory characteristics of exenatide-given patients in endocrinology clinic of a university hospital

Objective: Exenatide has high affinity on binding GLP - 1 receptors. Endogenous GLP - 1 effects glucose -dependent insulin secretion, delayed gastric emptying, suppression of glucagon, inhibition of appetite, and shows effects of enhancing β - cell mass. It is usually use in the treatment of type 2 obese diabetic patients, whose treatment not be obtained with metformin and sulfonylurea or both. It was added to insulin therapy, because it provides better glycemic control and weight loss in cases which have high level of blood glucose with oral antidiabetic. In our study we planned to share the patients treated with exenatide in our clinic for a period of at least 4 months and discuss their biochemical and clinical parameters. Methods: In this study we evaluated 26 patients (2 males, 24 females) who admitted our clinic between July 2011 and December 2013 and who followed up at least 4 months (mean: 7.3) All of the patients were using metformin in combination with oral antidiabetic drug therapy, while 6 patients were receiving insulin therapy in addition to metformin. Results: After treatment, HemoglobineA1c decrease were found 0.98 % for women and 1.4% for men and of weight loss were found 0.64% for women and 0.57% for men, measurements of body mass index were decreased 0.61% for females and 0.56% for men. Conclusion: We determined that; addition of exenatide treatment to Insulin, metformin or oral antidiabetic therapy combination in obese patients leads to weight loss and decrease Hemoglobin A1c levels.

Keywords:

Exenatide, GLP-1, Diabetes mellitus,

PDF

___

Elrick H, Stimmler L, Hlad CJ, Arai Y. Plasma insulin re- sponse to oral and ıntravenous glucose administration. J Clin Endocrinol Metab 1964;24:1076-1082.
Vilsbİll T, Holst JJ. Incretins, insulin secretion and type 2 diabetes mellitus. Diabetologia 2004;47:357-366.
Buse JB, Henry RR, Han J, et al. Effects of exenatide (ex- endin-4) on glycemic control over 30 weeks in sulfonyl- urea-treated patients with type 2 diabetes. Diabetes Care 2004;27:2628-2635.
Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 2003;26:2929-2940.
Gallwitz B. Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. Treat Endocrinol 2005;4:361-370.
Thorens B, Porret A, Bühler L, et al. Cloning and functional expression of the human islet GLP-1 recepıtor. Demonstra- tion that exendin-4 is an agonist and exendin-(9-39) an an- tagonist of the receptor. Diabetes 1993;42:1678-1682.
Kolterman OG, Kim DD, Shen L, et al. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus.Am J Health Syst Pharm 2005;62:173-181.
Kolterman OG, Buse JB, Fineman MS, et al. Synthetic ex- endin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2003;88:3082-3089.
Tang-Christensen M, Larsen PJ, Göke R, et al. Central ad- ministration of GLP-1-(7-36) amide inhibits food and water intake in rats. Am J Physiol 1996;271:848-856.
Xu G, Stoffers D.A, Habener J.F, Bonner-Weir S. Exendin-4 stimulates both beta-cell replication and neogenesis, result- ing in inıcreased beta-cell mass and improved glucose tol- erance in diabetic rats. Diabetes 1999;48:2270-2276.
Egan J.M, Clocquet A.R, Elahi D, The insulinotropic effect of acute exendin-4 administered to humans: comparison of nondiabetic state to type 2 diabetes. J Clin Endocrinol Metab 2002;87:1282-1290.
De Fronzo R.A, Ratner R.E, Han J, et al. Effects of exena- tide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care 2005;28:1092-1100.
Kim D, Mac Conell L, Zhuang D, et al. Effects of once- weekly dosing of a long-acting release formulation of ex- enatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care 2007;30:1487-93.
Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: Systematic review and meta- analysis. JAMA 2007;298:194-206.
Ratner RE, Maggs D, Nielsen LL, et al. Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Diabetes Obes. Metab 2006;8:419- 428.
Barnett AH, Burger J, Johns D, et al. Tolerability and ef- ficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: A multinational, randomized, open-label, two-period, crossover noninferiority trial. Clin. Ther 2007;29:2333-2348.
Heine RJ, Van Gaal LF, Johns D, et al. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 2005;143:559-569.
Nauck MA, Meininger G, Sheng D, et al. Efficacy and safe- ty of the dipeptidyl peptidase-4 inhibitor, sitagliptin, com- pared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2007;9:194-205.
Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005;28:1083-1091.
Zinman B, Hoogwerf BJ, Durán García S, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 2007;146:477-485.
Fagenholz PJ, Castillo CF, Harris NS, et al. Increasing Unit- ed States hospital admissions for acute pancreatitis, 1988- 2003. Ann Epidemiol 2007;17:491-497.
Noel RA, Braun DK, Patterson RE, Bloomgren GL. In- creased risk of acute pancreatitis and biliary disease ob- served in patients with type 2 diabetes: a retrospective co- hort study. Diabetes Care 2009;32:834-838.