Özen ÖZ GÜL, Pınar ŞİŞMAN, Soner CANDER, Canan ERSOY

Sitagliptin Monoterapisi ile Kombinasyon Tedavilerinin Karşılaştırılması

Çalışmamızda sitagliptinin monoterapide ve kombinasyon (metformin veya pioglitazon) tedavilerinde kullanımlarının glisemik kontrol, lipid profili ve insülin direnci üzerine etkilerinin karşılaştırılması amaçlanmıştır. Yeni tanı almış ve daha önce antidiyabetik tedavi almamış olan toplam 46 tip 2 diyabetik hasta çalışmaya dahil edildi. Hastalara rastgele olarak sitagliptin (grup 1), sitagliptin+metformin (grup 2), sitagliptin+pioglitazon (grup 3) tedavileri başlandı. Tedavide sitagliptin 100mg/gün, metformin 2000mg/gün ve pioglitazon 30mg/gün dozlarında kullanıldı. Altı aylık izlem süresini tüm hastalar tamamladı. Hastalar başlangıçta ve çalışma sonunda antropometrik ölçümler, glisemik parametreler ve lipid düzeyleri açısından değerlendirildi. Hastaların başlangıç antropometrik ölçümleri, glisemik parametreleri ve lipid profilleri benzerdi. Altıncı ay sonunda yapılan değerlendirmede grup 1’de istatistiksel anlamlı vücut kitle indeksi (VKİ) düşüşü gözlenirken, grup 2 ve 3’te istatistiksel anlamlı değişiklik saptanmadı. Hemoglobin A1c her üç grupta da istatistiksel olarak anlamlı düzeyde azaldı, gruplar arasında ise istatistiksel anlamlı farklılık saptanmadı. Altıncı ay sonunda serum trigliserid düzeyleri grup 3’te anlamlı olarak azalırken diğer lipid profili üzerine etkileri açısından her üç grup arasında farklılık saptanmadı. HOMA-IR değerlendirildiğinde 6 ay sonunda grup 1 ve grup 2’de farklılık saptanmazken, grup 3’te anlamlı azalma olduğu görüldü (p<0.05). Çalışmamız sonucunda sitagliptin monoterapisi sitagliptin+metformin ve sitagliptin+pioglitazon kombinasyon tedavilerinin glisemik değerler ve lipid profili üzerine olan etkileri benzerdi. Sitagliptin pioglitazon kombinasyon tedavisinin insülin direnci ve trigliserid düzeylerini düşürmede daha üstün olduğu saptanmıştır.

Anahtar Kelimeler:

Tip 2 diyabet, insülin direnci, sitagliptin, pioglitazon

Comparison of Sitagliptin Monotherapy with Combination Therapy

The aim of this study was to compare the effects of sitagliptin in monotherapy and combination (metformin or pioglitazone) treatments on glycemic control, lipid profile and insulin resistance. A total of 46 type 2 diabetic patients, who were newly diagnosed and who had not previously received antidiabetic therapy, were included in the study. Patients were randomly assigned to receive sitagliptin (group 1), sitagliptin + metformin (group 2) or sitagliptin + pioglitazone (group 3). Sitagliptin 100 mg/day, metformin 2000 mg/day and pioglitazone 30 mg/day were used in the treatment. All patients completed the six-month follow-up period. Patients were evaluated at baseline and at the end of the study in terms of anthropometric measurements, glycemic parameters and lipid levels. Initial anthropometric measurements, glycemic parameters and lipid profiles were similar. At the end of the sixth month, a statistically significant decrease in body mass index (BMI) was observed in group 1, while there was no statistically significant difference in group 2 and 3. Hemoglobin A1c was significantly decreased in all three groups and no statistically significant difference was found between the groups. Serum triglyceride levels were significantly decreased in group 3 at the end of the sixth month and no difference was found between the three groups in terms of their effects on the other lipid profile. When HOMA-IR was evaluated, there was no significant difference in group 1 and group 2 at the end of 6 months, whereas there was a significant decrease in group 3 (p <0.05). The effects of sitagliptin monotherapy, sitagliptin+metformin and sitagliptin+pioglitazone combination treatments on glycemic values and lipid profile were similar. Sitagliptin+pioglitazone combination therapy was found to be superior in reducing insulin resistance and triglyceride levels.

Keywords:

Type 2 diabetes, insulin resistance, sitagliptin, pioglitazone,

PDF

___

1. Yokoh H, Kobayashi K, Sato Y, et al, on behalf of the SUCCESS Study Group. Eficacy and safety of the dipeptidil peptidase-4 inhibitor sitagliptin compared with alpha-glucısidase inhibitör in Japanese patients with type 2 diabetes inadequately controlled on metformin or pioglitazone alone (Study for an Ultimate Combination Therapy to Control Diabetes with sitagliptin-1): A multicenter, randomizes, open-label, non-inferiority trial. J Diabetes Invest. 2015; 6: 182-91.
2. Jameshorani M, Sayari S, Kiahashemi N, Motamed N. Comparative study on adding pioglitazone or sitagliptin to patients with type 2 diabetes mellitus insufficiently controlled with metformin. Open Access Maced J Med Sci. 2017; 5: 955-62.
3. Nathan DM, Buse JB, Davidson MB, et al. American Diabetes Association; European Association for Study of Diabetes. Diabetes Care 2009; 32: 193-203.
4. Abdul-Ghani MA, Puckett C, Triplitt C, et al. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficasy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes Metab 2015; 17: 267-75.
5. Mikhail N. Combination therapy with DPP-4 inhibitors and pioglitazone in type 2 diabetes: theoretical consideration and therapeutic potential. Vasc Health Risk Manag 2008; 4: 1221-7.
6. Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H, Sitagliptin Study 023 Group. Efficacy and safety of the dipeptidil peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia 2006; 49: 2564-71.
7. Bailey CJ, Turner RC. Metformin. N Eng J Med 1996; 334: 574-9.
8. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-65.
9. Aschner P, Kipnes M, Lunceford JK, Sanchez M, Mickel C, Williaams-Herman DE, Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care 2006; 29: 2632-7.
10. Charbonnel B, Karasik A, Liu J, Wu M, Meininger G. Efficacy and safety of the Dipeptidyl Peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006; 29: 2638-43.
11. Aronoff S, Rosenblatt S, Braitwaite S, Egan JW, Mathisen AL, Schneider RL. Pioglitazoe hydrocloride monotherapy improves glycemik control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled doşe-response study. The pioglitazone 001 Study Group. Diabetes Care 2000; 23: 1605-11.
12. Kashiwagi A, Kadowaki T, Tajima N, et al. Sitagliptin added to treatment with ongoing pioglitazone for up to 52 weeks improves glycemic control in Japanese patients with type 2 diabetes. J Diabetes Investig 2011; 2: 381-90.
13. Kobayashi K, Yokoh H, Sato Y, et al, SUCCESS Study Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with α-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on sulfonylurea alone (SUCCESS-2): a multicenter, randomized, open-label, non-inferiority trial. Diabetes Obes Metab 2014; 16: 761-5.
14. Takihata M, Nakamura A, Tajima K, et al. Comparative study of sitagliptin with pioglitazone in Japanese type 2 diabetic patients: the COMPASS randomized controlled trial. Diabetes Obes Metab 2013; 15: 455-62.
15. Dormandy JA, Charbonnel B, Eckland DJA, et al, PROactive Investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (P>R>Ospective piogltAzone Clinical Trial In macrovascular Events): a randomized controlled trial. Lancet 2005; 366: 1279-89.
16. Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stain P; Sitagliptin Study 019 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomised, double-blind, plasebo-controlled, parallel-group study. Clin Ther 2006; 28: 1556-68.