SODYUM GLUKOZ KO-TRANSPORTER 2 İNHİBİTÖRLERİNİN PLEİOTROPİK ETKİLERİ

Abstract

Diabetes mellitus, insulin rezistansı, insulin sekresyonundaki bozukluk veya sekresyonunun olmayışından ya da bunların bir arada bulunmasından kaynaklanan hiperglisemi ile karakterize kronik metabolik bir hastalıktır. Diyabetik bireyler için iyi bir glisemik kontrol çok önemlidir. Ne yazık ki, diyabetik bireylerin pek çoğunda, kabul edilebilir bir glisemik kontrole ulaşılamamaktadır. Bu nedenle de diyabet ile ilgili komplikasyonlardan kaynaklanan morbidite ve mortalite yüksektir. Sodyum glukoz ko-transporter-2 (SGLT2) inhibitörleri, benzersiz etki mekanizmasına sahip, yeni bir antidiyabetik ilaç sınıfıdır. Bu çalışma, SGLT2 inhibitörlerinin pleiotropik etkilerine ilişkin genel bilgi sağlamaktadır. Bu amaçla, ilgili makaleler PubMed ve Uluslararası Farmasötik Özetler aracılığıyla taranmıştır. Taramada kullanılan anahtar kelimeler: “canagliflozin, dapagliflozin, empagliflozin, pleiotropic effects, sodium-glucose co transporter 2 inhibitors” olarak seçilmiştir.

Keywords

• Diyabet,diyabetik komplikasyonlar,pleiotropik etki,SGLT2 inhibitörleri

Pleiotropic Effects of Sodium - Glucose Co-Transporter 2 Inhibitors

Abstract

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia because of insulin resistance, diminished or absent insulin secretion or both. Good glycemic control is one of the most important issues for diabetic individual. Unfortunately, most of the diabetics fail to achieve acceptable glycemic control. Therefore, diabetes-associated morbidity and mortality is high resulting from complications. The sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a unique mechanism of action. This article provides an overview of pleiotropic effects of SGLT2 inhibitors. For this purpose, relevant articles were identified through searches of PubMed and International Pharmaceutical Abstracts by using the key words diabetes, canagliflozin, dapagliflozin, empagliflozin, pleiotropic effects, sodium-glucose co transporter 2 inhibitors.

Keywords

• Diabetes,diabetic complications,pleiotropic effect,SGLT2 inhibitors

References

1. Diabetes fact sheet. World Health Organisation website. Erişim 20. Ekim. 2015. http://www.who.int/mediacentre/factsheets/fs312/e n/.
2. Statistics about diabetes. American Diabetes Association website. Erişim 20. Ekim. 2015. http://www.diabetes.org/diabetesbasics/statistics/?lo c=db-slabnav.
3. The effect of intensive treatment of diabetes on the development of long-term complications ininsulin- dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl JMed. 1993; 329: 977-86.
4. Holman RP, Paul SK, Bethel MA. 10-year follow- up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008; 359: 1577-89.
5. American Diabetes Association. Approaches to glycemic treatment. Diabetes Care. 2015; 38: 41-8.
6. Whalen K, Miller S, Onge E. The role of sodium- glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes. Clin Ther. 2015; 37: 1150-66.
7. Bays H. Sodium Glucose Co-transporter Type 2 (SGLT-2) Inhibitors: Targeting the kidney to improve glycemic control in diabetes mellitus. Diabetes Ther. 2013; 4: 195-220.
8. Halimi S, Vergès B. Adverse effects and safety of SGLT-2 inhibitors. Diab Metab. 2014; 40: 28-34.

9. Ptaszynska A, Johnsson KM, Parikh SJ, de Bruin TW, Apanovitch AM, List JF. Safety profile of dapagliflozin for type 2 diabetes: pooled analysis of clinical studies for overall safety and rare events. Drug Saf. 2014; 37: 815-29.
10. Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013; 159: 262-74.
11. Lambers Heerspink HJ, de Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013; 15: 853-62.
12. Tikkanen I, Narko K, Zeller C, et al. EMPA-REG BP Investigators. Empagliflozin improves blood pressure in patients with type 2 diabetes (T2DM) and hypertension. In: Abstract 942 presented at the 49th European Association for the Study of Diabetes Annual Meeting, September 23–27, Barcelona, Spain. Diabetologia. 2013; 56: 377.
13. Weir MR, Januszewicz A, Gilbert RE, Lavalle Gonzalez FJ, Meininger G. Lower blood pressure (BP) with canagliflozin (cana) in subjects with type 2 diabetes mellitus (T2DM). Diabetes. 2013; 62: 1077.
14. Rohwedder K, Johnsson E, Parikh S. Reduced risk of hypoglycemic events with dapagliflozin vs. glipizide as add-on therapy in type 2 diabetes mellitus: 4-year data from a phase 3 study. In: Poster presented at 50th Annual meeting of the European Association for the Study of Diabetes. Vienna; 2014.
15. Leiter LA, Yoon KH, Arias P, et al. Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: a randomized, double-blind, phase 3 study diabetes care. 2014. 16. Sha S, Devineni D, Ghosh A, et al. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes. PLoS One. 2014; 9: 105638.
16. Nauck MA, Del Prato S, Durán-García S, et al. Durability of glycaemic efficacy over 2 years with dapagliflozin versus glipizide as add-on therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin. Diabetes Obes Metab. 2014; 16(11): 1111-20.
17. Scheen A. Pharmacokinetic and pharmacodynamics profile of empagliflozin, a sodium glucose cotransporter 2 inhibitor. Clin Pharmacokinet. 2014; 53(3): 213-25.
18. Rohwedder K, Johnsson E, Parikh S. Reduced risk of hypoglycemic events with dapagliflozin vs. glipizide as add-on therapy in type 2 diabetes mellitus: 4-year data from a phase 3 study. In: Poster presented at 50th Annual meeting of the European Association for the Study of Diabetes. Vienna; 2014.
19. Rosenstock J, Jelaska A, Zeller C, Kim G, Broedl UC, Woerle HJ; EMPA-REG BASALTM trial investigators. Impact of empagliflozin added on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: a 78-week randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2015; 17(10): 936-48.
20. Scheen A. Pharmacokinetic and pharmacodynamics profile of empagliflozin, a sodium glucose cotransporter 2 inhibitor. Clin Pharmacokinet. 2014; 53(3): 213-25.
21. Bolinder J, Ljunggren Ö, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014;16: 159-69.
22. Ruggenenti P, Porrini EL, Gaspari F, et al. GFR Study Investigators. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care. 2012; 35: 2061-8.