A Sweet Dream with SGLT2 Inhibitors

Yıl 2021, , 237 - 240, 29.08.2021

Utku Erdem Soyaltin , Şevki Çetinkalp , Ilgın Yıldırım Şimşir , Ayşe Kandemir , Meltem Seziş

https://doi.org/10.25048/tudod.900107

Cited By: 1

Öz

Glucose is an osmotic agent in the peritoneal dialysis fluid (PDF) to absorb water, sodium and other toxins. Glucose absorption from PDF to blood impairs peritoneal dialysis (PD) efficiency and cause glycemic burden. This extra glycemic load leads to poor glycemic control in diabetic dialysis patients with PD program.
Studies have shown sodium-glucose co-transporter (SGLT)-2 expression in peritoneal mesothelial cells. Blockade of peritoneal SGLT reduced blood glucose increment and increased peritoneal glucose retention in mice. In rat models, it was shown that high glucose PDF promotes the peritoneal fibrosis by upregulating the expression of glucose transporter (GLUT) and SGLT, and addition of phlorizin to PDF leads to downregulation of GLUT and SGLT expression and reduced peritoneal degeneration.
According to these information, we want to share our experience of using empagliflozin in a poor glycemic controlled type 2 diabetic patient, who was on PD program for end-stage renal disease. We hypothesized that if we administer empagliflozin to our patient we can reduce glycemic burden caused by PDF and increase the ultrafiltration volume.

Anahtar Kelimeler

SGLT2 inhibitors, peritoneal dialysis, glycemic burden

SGLT2 İnhibitörleri ile Tatlı Bir Rüya

Öz

Glukoz; su, sodyum ve diğer toksinleri absorbe için periton diyaliz sıvısında bulunan ozmotik bir ajandır. Periton diyaliz sıvısından kana glukoz emilimi periton diyalizi (PD) verimini bozar ve glisemik yüke neden olur. Bu ekstra glisemik yük, PD programındaki diyabetik diyaliz hastalarında kötü glisemik kontrole yol açar. Çalışmalar, peritondaki mezotelyal hücrelerde sodyum-glikoz ko-transporter-2 (SGLT2) ekspresyonunu göstermiştir. Peritoneal SGLT'nin blokajı, farelerde kan glukoz artışını düşürmüş ve peritonal glukoz tutulmasını artırmıştır. Sıçan modellerinde, yüksek glukozlu periton diyaliz sıvısının, glikoz taşıyıcılarını (GLUT) ve SGLT'nin ekspresyonunu artırarak peritoneal fibrozu indüklediği ve periton diyaliz sıvısına florizin eklenmesinin GLUT ve SGLT ekspresyonunu azaltarak ve periton dejenerasyonunun azalmasına neden olduğu gösterilmiştir. Bu bilgilere göre, son dönem böbrek hastalığı için PD programında olan kötü glisemik kontrollü tip 2 diyabetik bir hastada empagliflozin kullanma deneyimimizi paylaşmak istiyoruz. Hastamıza empagliflozin uygulayarak, periton diyaliz sıvısının neden olduğu glisemik yükü azaltabileceğimizi ve ultrafiltrasyon hacmini artırabileceğimizi varsaydık.

Anahtar Kelimeler

SGLT2 inhibitörleri, periton diyalizi, glisemik yük

Kaynakça

• References 1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. doi: 10.1056/NEJMoa1504720.
• 2. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-57. doi: 10.1056/NEJMoa1611925.
• 3. Birkeland KI, Jørgensen ME, Carstensen B, et al. Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis. Lancet Diabetes Endocrinol. 2017;5(9):709-717. doi: 10.1016/S2213-8587(17)30258-9.
• 4. Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2017;5(11):864-876. doi: 10.1016/S2213-8587(17)30308-X.
• 5. Chen J, Fan F, Wang JY, et al. The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis. Sci Rep. 2017;7:44128. doi: 10.1038/srep44128.
• 6. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303.
• 7. Mehrotra R, Ravel V, Streja E, et al. Peritoneal equilibration test and patient outcomes. Clin J Am Soc Nephrol. 2015;10(11):1990-2001. doi: 10.2215/CJN.03470315.
• 8. Debray-García Y, Sánchez EI, Rodríguez-Muñoz R, Venegas MA, Velazquez J, Reyes JL. Diabetes and exposure to peritoneal dialysis solutions alter tight junction proteins and glucose transporters of rat peritoneal mesothelial cells. Life Sci. 2016;161:78-89. doi: 10.1016/j.lfs.2016.07.018.
• 9. Scheen AJ. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Pharmacokinet. 2014;53(3):213-225. doi: 10.1007/s40262-013-0126-x.
• 10. Macha S, Mattheus M, Halabi A, Pinnetti S, Woerle HJ, Broedl UC. Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. Diabetes Obes Metab. 2014;16(3):215-22. doi: 10.1111/dom.12182.