Liraglutidin tiroid fonksiyon testleri üzerine etkisinin araştırılması

Amaç: Liraglutid, gıda alımına yanıt olarak intestinal L hücrelerinden salgılanan bir inkretin hormon olan glukagon benzeri peptid-1 reseptör agonistidir (GLP‑1 RA). Glukoz bağımlı insülin sekresyonunu uyarır ve hepatik glukagon sekresyonunu azaltır. Ayrıca, mide boşalmasını yavaşlatır ve tokluk hissi sağlar. Obezite tedavisinde kilo verme amaçlı kullanılan ilk GLP‑1 RA'dir. Liraglutidin tiroid fonksiyon testlerine etkisi bilinmemektedir ve bilgimiz dahilinde bu konuda herhangi bir çalışma bulunmamaktadır. Amacımız, liraglutid tedavisi öncesi ve tedaviden 6 ay sonrasındaki tiroid fonksiyon testlerini, diğer biyokimyasal ve hemogram parametrelerini karşılaştırmaktır. Gereç ve Yöntemler: Burdur Devlet Hastanesi'nde Ocak 2021-Ocak 2023 tarihleri arasında obezite tedavisi nedeniyle en az 6 aydır liraglutide kullanan 18-65 yaş arası hastalar çalışmaya alındı. Bulgular: Çalışma süresince tiroid hastalığı olmayan ve liraglutid kullanan 51 hasta (39 kadın, 12 erkek) vardı. On iki hasta, tedavinin 6. ayı tamamlanmadan liraglutid kullanımını bıraktı. Ağırlık, vücut kitle indeksi, açlık serum glukozu, hemoglobin A1C (HbA1c), düşük yoğunluklu lipoprotein (LDL), trigliserit ve tiroid uyarıcı hormon (TSH) değerleri tedavinin 6. ayında anlamlı olarak düşüktü. Serbest tiroksin (sT4) ve serbest triiyodotironin (sT3) değerleri benzerdi. Diğer biyokimyasal ve hemogram parametrelerinde tedavi öncesi ve tedavi sonrası 6 ay arasında fark yoktu. Sonuç: TSH değerlerinde anlamlı azalma ve metabolik parametrelerde düzelme saptadık, ancak tiroid hormon düzeylerinde farklılık yoktu.

Anahtar Kelimeler:

tiroid, liraglutid, obezite, tiroid uyarıcı hormon (TSH)

Investigation the impact of liraglutide on the thyroid function tests

Aim: Liraglutide is a once-daily glucagon-like peptide-1 receptor agonist (GLP‑1 RA) which is an incretin hormone secreted from intestinal L cells in response to nutritional intake and stimulates glucose-dependent insulin secretion, decreases hepatic glucagon secretion, slows gastric emptying, provides a feeling of satiety and is the first GLP‑1 RA to be indicated for weight loss treatment for obesity. The impact of liraglutide on thyroid function tests is unknown and to the best of our knowledge, there are no studies on this regard. Our aim is to compare thyroid function tests, other biochemical and hemogram parameters before and 6 months after liraglutide treatment. Material and Methods: The patients, 18-65 years old, who used liraglutide for at least 6 months due to obesity treatment between January 2021 and January 2023 in Burdur State Hospital were included. Results: There were 51 patients (39 female, 12 male) using liraglutide without thyroid disease during the study period. Twelve patients discontinued liraglutide use before the 6th month of treatment was completed. Weight, body mass index (BMI), fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), low-density lipoprotein (LDL), triglyceride and thyroid-stimulating hormone (TSH) values were significantly lower at the 6th month of treatment. Free thyroxine (FT4) and free triiodothyronine (FT3) values were similar. and there was no difference other biochemical and hemogram parameters between before and 6 months after treatment Conclusion: We found a significant decrease in TSH values and improvement in metabolic parameters, but no change in thyroid hormone levels.

Keywords:

thyroid, liraglutide, obesity, thyroid-stimulating hormone (TSH),

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1. Jacobsen LV, Flint A, Olsen AK, Ingwersen SH. Liraglutide in Type 2 Diabetes Mellitus: Clinical Pharmacokinetics and Pharmacodynamics. Clin Pharmacokinet 2016; 55: 657-72.
2. Fava S. Glucagon-like peptide 1 and the cardiovascular system. Curr Diabetes Rev 2014; 10: 302-10.
3. Aroda VR, Ratner R. The safety and tolerability of GLP-1 receptor agonists in the treatment of type 2 diabetes: a review. Diabetes Metab Res Rev 2011; 27: 528-42.
4. Körner M, Stöckli M, Waser B, Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med 2007; 48: 736-43. 343
5. Vilsboll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ 2012; 344: d7771.
6. Garber AJ. Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability. Diabetes Care 2011; 34: 279-84.
7. Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond. Drugs Context 2015; 4: 212283.
8. Jimeno C, Kho S, de Los Santos GK, Buena-Bobis N, Villa M. The Multicenter, Open-Label, Observational LEAD-Ph Study: Real-World Safety and Effectiveness of Liraglutide in Filipino Participants with Type 2 Diabetes. J ASEAN Fed Endocr Soc 2018; 33: 114-23.
9. Saraiva FK, Sposito AC. Cardiovascular effects of glucagon-like peptide 1 (GLP-1) receptor agonists. Cardiovasc Diabetol 2014; 13: 142.
10. Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-22.
11. Saxenda package insert. Available at http://www.novo-pi.com/ saxenda.pdf.
12. Albores-Saavedra JA, Krueger JE. C-cell hyperplasia and medullary thyroid microcarcinoma. Endocr Pathol 2001; 12: 365-77.
13. Bjerre Knudsen L, Madsen LW, Andersen S, et al. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 2010; 151: 1473-86.
14. Jung MJ, Kwon SK. Expression of glucagon-like Peptide-1 receptor in papillary thyroid carcinoma and its clinicopathologic significance. Endocrinol Metab (Seoul) 2014; 29: 536-44.
15. Elashoff M, Matveyenko AV, Gier B, Elashoff R, Butler PC. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology 2011; 141: 150-6.
16. Gough SC. Liraglutide: from clinical trials to clinical practice. Diabetes Obes Metab 2012; 14: 33-40.
17. Sencar ME, Sakiz D, Calapkulu M, et al. The Effect of Exenatide on Thyroid-Stimulating Hormone and Thyroid Volume. Eur Thyroid J 2019; 8: 307-11.
18. Köseoğlu D, Özdemir Başer Ö, Berker D, Güler S. Exenatide treatment reduces thyroid gland volume, but has no effect on the size of thyroid nodules. Acta Endocrinol (Buchar) 2020; 16: 275-79.
19. Tee SA, Tsatlidis V, Razvi S. The GLP-1 receptor agonist exenatide reduces serum TSH by its effect on body weight in people with type 2 diabetes. Clin Endocrinol (Oxf ) 2023; 1- 8.
20. Fujita N, Kato K, Abe S, Naganawa S. Variation in thyroid volumes due to differences in the measured length or area of the cross- sectional plane: A validation study of the ellipsoid approximation method using CT images. J Appl Clin Med Phys 2021; 22: 15-25.
21. Pappa T, Alevizaki M. Metformin and thyroid: an update. Eur Thyroid J 2013; 2:22-8.
22. Cappelli C, Rotondi M, Pirola I, et al. Thyrotropin levels in diabetic patients on metformin treatment. Eur J Endocrinol 2012; 167:261-5.
23. Satoh F, Beak SA, Small CJ, et al. Characterization of Human and Rat Glucagon-Like Peptide-1 Receptors in the Neurointermediate Lobe: Lack of Coupling to Either Stimulation or Inhibition of Adenylyl Cyclase, Endocrinology 2000;141: 1301–9.
24. Biondi B. Thyroid and obesity: an intriguing relationship. J Clin Endocrinol Metab 2010; 95:3614-7.
25. MacCuish A, Razvi S, Syed AA. Effect of weight loss after gastric bypass surgery on thyroid function in euthyroid people with morbid obesity. Clin Obes 2012; 2: 25-8.
26. Wang X, Gao X, Han Y, et al. Causal Association Between Serum Thyrotropin and Obesity: A Bidirectional, Mendelian Randomization Study. J Clin Endocrinol Metab 2021; 106: 4251-9.
27. Guan B, Chen Y, Yang J, Yang W, Wang C. Effect of Bariatric Surgery on Thyroid Function in Obese Patients: a Systematic Review and Meta-Analysis. Obes Surg 2017; 27: 3292-3305.