Evaluation of sitagliptin therapy on the levels of fibroblast growth factor-19 (FGF19) in patients with Type 2 diabetes

Year 2022, , 34 - 40, 01.04.2022

Özen Öz Gül , Soner Cander

https://doi.org/10.46310/tjim.1070223

Abstract

Introduction: The specific association between sitagliptin and Fibroblast Growth Factor-19 (FGF19) is yet to be clarified. In this study, we aimed to investigate the effect of sitagliptin therapy on the levels of FDF19 in patients with type 2 diabetes mellitus (T2DM).
Methods: A total of 35 patients newly diagnosed type 2 diabetes, and who had not received antidiabetic treatment before were included in this study. Sitagliptin therapy was administered as 100 mg/day. Patients’ demographic, anthropometric features, glycaemic variables, lipid profiles and FGF19 values were evaluated at the baseline and at the 3rd month of the treatment and the obtained data were compared.
Results: The mean age of the patients was 53.34 ± 8.09 years. The mean weight, body mass index (BMI), hip circumference, postprandial blood glucose and glycosylated haemoglobin A1c (HbA1c) values were statistically significantly lower at the 3rd month of the treatment compared to the baseline values (for all, p<0.05). The mean FGF19 was found as 84.37±64.23 pg/mL at the baseline and 86.06±44.10 pg/mL at the 3rd month of the treatment and the difference was not statistically significant (p=0.789). A moderate negative correlation was found between FGF19, total cholesterol and low density lipoprotein cholesterol (LDL-c), and a moderate positive correlation between FGF19 and triglycerides.
Conclusion: This study did not show a significant effect of sitagliptin therapy on FGF19. T2DM variables such as postprandial blood glucose and HbAc1 were significantly improved. FGF19 was moderately correlated with total cholesterol and LDL-c in negative direction and with triglycerides in positive direction.

Keywords

Type 2 diabetes mellitus, fibroblast growth factor-19, sitagliptin, hyperglycemia, blood glucose

References

• Massey W, Brown JM. The gut microbial endocrine organ in type 2 diabetes. Endocrinology. 2021 Feb 1;162(2):bqaa235. doi: 10.1210/endocr/bqaa235.
• International Diabetes Federation. IDF diabetes Atlas. 9th ed. Brussels, Belgium: International Diabetes Federation; 2019.
• Rysz J, Gluba-Brzózka A, Mikhailidis DP, Banach M. Fibroblast growth factor 19-targeted therapies for the treatment of metabolic disease. Expert Opin Investig Drugs. 2015 May; 24(5):603-10. doi: 10.1517/13543784.2015.1006357.
• FangQ,LiH,SongQ,YangW,HouX,MaX,LuJ,XuA,Jia W. Serum fibroblast growth factor 19 levels are decreased in Chinese subjects with impaired fasting glucose and inversely associated with fasting plasma glucose levels. Diabetes Care. 2013 Sep;36(9):2810–4. doi: 10.2337/dc12-1766.
• Chung JO, Park SY, Cho DH, Chung DJ, Chung MY. Relationship between fibroblast growth factor 19 and diabetic retinopathy in patients with type 2 diabetes mellitus. Diabetes Metab Syndr Obes. 2021 Dec 3;14:4715-4721. doi: 10.2147/ DMSO.S339954.
• Devin JK, Nian H, Celedonio JE, Wright P, Brown NJ. Sitagliptin decreases visceral fat and blood glucose in women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 2020 Jan 1; 105(1): 136-51. doi: 10.1210/clinem/dgz028.
• Fan M, Li Y, Zhang S. Effects of sitagliptin on lipid profiles in patients with type 2 diabetes mellitus: a meta-analysis of randomized clinical trials. Medicine (Baltimore). 2016 Jan;95(2):e2386. doi: 10.1097/MD.0000000000002386.
• HaoY,ZhouJ,ZhouM,MaX,LuZ,GaoM,PanX,TangJ, Bao Y, Jia W. Serum levels of fibroblast growth factor 19 are inversely associated with coronary artery disease in chinese individuals. PLoS One. 2013 Aug 7;8(8):e72345. doi: 10.1371/ journal.pone.0072345.
• Fu L, John LM, Adams SH, Yu XX, Tomlinson E, Renz M, Williams PM, Soriano R, Corpuz R, Moffat B, Vandlen R, Simmons L, Foster J, Stephan JP, Tsai SP, Stewart TA. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology. 2004 Jun;145(6):2594-603. doi: 10.1210/en.2003-1671.
• Stejskal D, Karpísek M, Hanulová Z, Stejskal P. Fibroblast growth factor-19: development, analytical characterization and clinical evaluation of a new ELISA test. Scand J Clin Lab Invest. 2008;68(6):501-7. doi: 10.1080/00365510701854967.
• Herman GA, Stein PP, Thornberry NA, Wagner JA. Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes: focus on sitagliptin. Clin Pharmacol Ther. 2007 May;81(5):761- 7. doi: 10.1038/sj.clpt.6100167.
• Sakura H, Hashimoto N, Sasamoto K, Ohashi H, Hasumi S, Ujihara N, Kasahara T, Tomonaga O, Nunome H, Honda M, Iwamoto Y; JAMP Study Investigators. Effect of sitagliptin on blood glucose control in patients with type 2 diabetes mellitus who are treatment naive or poorly responsive to existing antidiabetic drugs: the JAMP study. BMC Endocr Disord. 2016 Dec 1;16(1):70. doi: 10.1186/s12902-016-0149-z.
• Shima KR, Ota T, Kato KI, Takeshita Y, Misu H, Kaneko S, Takamura T. Ursodeoxycholic acid potentiates dipeptidyl peptidase-4 inhibitor sitagliptin by enhancing glucagon- like peptide-1 secretion in patients with type 2 diabetes and chronic liver disease: a pilot randomized controlled and add-on study. BMJ Open Diabetes Res Care. 2018 Mar 17;6(1):e000469. doi: 10.1136/bmjdrc-2017-000469.
• Arnetz L, Hage C, Brismar K, Catrina SB, Norhammar A, Lundman P, Wallander M, Ryden L, Mellbin L. Copeptin, insulin-like growth factor binding protein-1 and sitagliptin: A report from the BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction study. Diab Vasc Dis Res. 2016 Jul;13(4):307-11. doi: 10.1177/1479164116635997.
• Owen BM, Mangelsdorf DJ, Kliewer SA. Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21. Trends Endocrinol Metab. 2015 Jan;26(1):22-9. doi: 10.1016/j. tem.2014.10.002.
• XuB,ShenT,ChenL,XiaJ,ZhangC,WangH,YuM,LeiT. The effect of sitagliptin on lipid metabolism of fatty liver mice and related mechanisms. Med Sci Monit. 2017 Mar 19;23:1363- 70. doi: 10.12659/msm.900033.