GLP-1 Reseptör Agonisti Tedavisinin Metabolik Parametreler ve Kardiyovasküler Risk Üzerindeki Etkisi: Gerçek Yaşam Çalışması

Öz

Özet Arka plan: Glukagon benzeri peptid-1 (GLP-1) reseptör agonistlerinin, obezite ve/veya tip 2 diyabetli hastalarda metabolik parametreleri iyileştirdiği ve kardiyovasküler riski azaltabileceği gösterilmiştir. Bu çalışma, semaglutidin üç aylık tedavi süresi boyunca antropometrik, metabolik ve kardiyovasküler risk parametreleri üzerindeki etkilerini değerlendirmeyi amaçlamıştır. Yöntemler: Toplam 187 hasta semaglutid tedavisi aldı ve başlangıçta (0. ay) ve üç ay sonra (3. ay) hastalar değerlendirildi. Antropometrik ölçümler, laboratuvar parametreleri ve Kardiyovasküler Skor-2 sonuçları kaydedildi. Değişiklikler Wilcoxon testi kullanılarak analiz edildi ve çalışma süresi boyunca yüzdesel değişiklikler hesaplandı. Sonuçlar: Üç ay sonra, vücut ağırlığında (%-4,9, p < 0,001), BMI'da (%-0,6, p < 0,001), sistolik kan basıncında (%-4,7, p < 0,001), diyastolik kan basıncında (%-4,6, p < 0,001), açlık kan şekerinde (%-5,6, p < 0,001), HbA1c'de (%-0,4, p < 0,001) ve LDL kolesterolde (%-10,5, p < 0,001) anlamlı azalmalar gözlemlendi. ALT, AST, kreatinin veya HDL düzeylerinde anlamlı bir değişiklik kaydedilmedi. Kardiyovasküler Skor-2, 8,8 ± 5,2'den 7,4 ± 4,7'ye anlamlı derecede düştü (p < 0,001). Düşük risk kategorisindeki hasta oranı %27'den %47'ye yükselirken, yüksek risk kategorisindeki hasta oranı %83'ten %46'ya düştü. Sonuçlar: Üç aylık semaglutid tedavisi, metabolik parametrelerde önemli iyileşme sağladı ve hastalarda kardiyovasküler riskte olumlu bir azalmaya yol açtı. Bu bulgular, GLP-1 reseptör agonistlerinin klinik uygulamadaki potansiyel kardiyoprotektif etkilerini desteklemektedir. Anahtar Kelimeler: GLP-1 agonisti, semaglutid, kardiyovasküler risk, obezite, HbA1c

Anahtar Kelimeler

• GLP-1 agonisti
• semaglutid
• kardiyovasküler risk
• obezite
• HbA1c

Impact of GLP-1 Receptor Agonist Therapy on Metabolic Parameters and Cardiovascular Risk: A Real-World Study

Öz

Abstract Background: Glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to improve metabolic parameters and may reduce Cardiovascular risk profile of individuals diagnosed with obesity and/or type 2 diabetes. This study aimed to evaluate the effects of semaglutide on anthropometric, metabolic, and cardiovascular risk parameters over three months of treatment. Methods: A total of 187 patients received semaglutide therapy and were assessed at baseline (0th month) and after three months (3rd month). Anthropometric measurements, laboratory parameters, and cardiovascular Score-2 were recorded. Changes were analyzed using the Wilcoxon signed-rank test, and percentage changes over the study period were calculated. Results: After three months, considerable declines were observed in body weight (−4.9%, p < 0.001), BMI (−0.6%, p < 0.001), systolic blood pressure (−4.7%, p < 0.001), diastolic blood pressure (−4.6%, p < 0.001), fasting blood glucose (−5.6%, p < 0.001), HbA1c (−0.4%, p < 0.001), and LDL cholesterol (−10.5%, p < 0.001). No significant changes were noted in ALT, AST, creatinine, or HDL levels. Cardiovascular Score-2 significantly decreased from 8.8 ± 5.2 to 7.4 ± 4.7 (p < 0.001). Risk distribution changed markedly, reflecting an expansion of the low-risk group from 27 to 47 alongside a contraction of the high-risk group from 83 to 46. Conclusions: Three months of semaglutide treatment significantly improved metabolic parameters and resulted in a favorable decline in cardiovascular risk among patients. Collectively, the data point toward a beneficial cardiovascular impact of GLP-1 receptor agonists in real-world practice. Keywords: GLP-1 agonist, semaglutide, cardiovascular risk, obesity, HbA1c

Anahtar Kelimeler

• GLP-1 agonist
• semaglutide
• cardiovascular risk
• obesity
• HbA1c

Etik Beyan

The research protocol received approval from the Institutional Review Board (01.10.2025, decision no: 2025-19/6) and was implemented in line with the ethical standards outlined in the Declaration of Helsinki. All individuals provided written informed consent before participation.

Kaynakça

1. Booth GL, Kapral MK, Fung K, Tu JV. Recent trends in cardiovascular complications among men and women with and without diabetes. Diabetes Care. 2006;29(1):32-37. doi:10.2337/diacare.29.01.06.dc05-1228
2. Haffner SJ, Cassells H. Hyperglycemia as a cardiovascular risk factor. Am J Med. 2003;115(Suppl 8A):6S-11S. doi:10.1016/j.amjmed.2003.09.009
3. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren WM, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Atherosclerosis. 2012;223(1):1-68. doi:10.1016/j.atherosclerosis.2012.05.007
4. Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev. 1999;20(6):876-913. doi:10.1210/edrv.20.6.0385
5. Wei Y, Mojsov S. Tissue-specific expression of the human receptor for glucagon-like peptide-1: brain, heart and pancreatic forms have the same deduced amino acid sequences. FEBS Lett. 1995;358:219-224. doi:10.1016/0014-5793(94)01430-9
6. 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;48:736-743. doi:10.2967/jnumed.106.038679
7. Saraiva FK, Sposito AC. Cardiovascular effects of glucagon-like peptide 1 (GLP-1) receptor agonists. Cardiovasc Diabetol. 2014;13:142. doi:10.1186/s12933-014-0142-7
8. Nyström T, Gutniak MK, Zhang Q, Zhang F, Holst JJ, Ahrén B, Sjöholm A. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004;287:E1209-E1215. doi:10.1152/ajpendo.2004

9. Hullon D, Janiec K, Florova V, Trach A, Volkova Y, Mnevets R. Glucagon-like peptide-1 receptor agonists and obesity paradox in heart failure with preserved ejection fraction: a systematic review. Cardiovasc Endocrinol Metab. 2025;14(4):e00344. doi:10.1097/XCE.0000000000000344
10. Ussher JR, Drucker DJ. Cardiovascular actions of incretin-based therapies. Circ Res. 2014;114(11):1788-1803. doi:10.1161/CIRCRESAHA.114.301958
11. Chang G, Zhang D, Yu H, Zhang P, Wang Y, Zheng A, Qin S. Cardioprotective effects of exenatide against oxidative stress-induced injury. Int J Mol Med. 2013;32(5):1011-1020. doi:10.3892/ijmm.2013.1475
12. Tan HC, Dampil OA, Marquez MM. Efficacy and safety of semaglutide for weight loss in obesity without diabetes: a systematic review and meta-analysis. J ASEAN Fed Endocr Soc. 2022;37(2):65-72. doi:10.15605/jafes.037.02.14
13. Verma S, Butler J, Borlaug BA, Davies M, Kitzman DW, Shah SJ, et al. Efficacy of semaglutide by sex in obesity-related heart failure with preserved ejection fraction. J Am Coll Cardiol. 2024;84:773-785. doi:10.1016/j.jacc.2024.05.069
14. Butler J, Shah SJ, Petrie MC, Borlaug BA, Abildstrøm SZ, Davies MJ, et al. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet. 2024;403:1635-1648. doi:10.1016/S0140-6736(24)00469-0
15. Yin Y, Zhang M, Cao Q, et al. Efficacy of GLP-1 receptor agonist-based therapies on cardiovascular events and cardiometabolic parameters in obese individuals without diabetes: a meta-analysis of randomized controlled trials. J Diabetes. 2025;17(4):e70082. doi:10.1111/1753-0407.70082
16. Shah SJ, Sharma K, Borlaug BA, Butler J, Davies M, Kitzman DW, et al. Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials. Eur Heart J. 2024;45:3254-3269. doi:10.1093/eurheartj/ehae406
17. Petrie MC, Borlaug BA, Butler J, Davies MJ, Kitzman DW, Shah SJ, et al. Semaglutide and NT-proBNP in obesity-related HFpEF. J Am Coll Cardiol. 2024;84:27-40. doi:10.1016/j.jacc.2024.04.038
18. Kramer CM, Borlaug BA, Zile MR, Ruff D, DiMaria JM, Menon V, et al. Tirzepatide reduces LV mass and paracardiac adipose tissue in obesity-related heart failure. J Am Coll Cardiol. 2024;85:S0735109724104147. doi:10.1016/j.jacc.2024.11.024
19. Solomon SD, Ostrominski JW, Wang X, Shah SJ, Borlaug BA, Butler J, et al. Effect of semaglutide on cardiac structure and function in patients with obesity-related heart failure. J Am Coll Cardiol. 2024;84:1587-1602. doi:10.1016/j.jacc.2024.08.021
20. Leite AR, Angélico-Gonçalves A, Vasques-Nóvoa F, et al. Effect of glucagon-like peptide-1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: a meta-analysis of placebo-controlled randomized trials. Diabetes Obes Metab. 2022;24(8):1676-1680. doi:10.1111/dom.14707
21. de Oliveira Almeida G, Nienkötter TF, Balieiro CCA, et al. Cardiovascular benefits of GLP-1 receptor agonists in patients living with obesity or overweight: a meta-analysis of randomized controlled trials. Am J Cardiovasc Drugs. 2024;24(4):509-521. doi:10.1007/s40256-024-00647-3
22. Singh S, Garg A, Tantry US, Bliden K, Gurbel PA, Gulati M. Safety and efficacy of glucagon-like peptide-1 receptor agonists on cardiovascular events in overweight or obese non-diabetic patients. Curr Probl Cardiol. 2024;49(3):102403. doi:10.1016/j.cpcardiol.2024.102403
23. Kristensen SL, Rørth R, Jhund PS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776-785. doi:10.1016/S2213-8587(19)30249-9
24. Ansari HUH, Qazi SU, Sajid F, et al. Efficacy and safety of glucagon-like peptide-1 receptor agonists on body weight and cardiometabolic parameters in individuals with obesity and without diabetes: a systematic review and meta-analysis. Endocr Pract. 2024;30(2):160-171. doi:10.1016/j.eprac.2023.11.007
25. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183
26. Blackman A, Foster GD, Zammit G, et al. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes (Lond). 2016;40(8):1310-1319. doi:10.1038/ijo.2016.52
27. Lund A, Knop FK, Vilsbøll T. Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes: differences and similarities. Eur J Intern Med. 2014;25(5):407-414. doi:10.1016/j.ejim.2014.01.019
28. Wadden TA, Bailey TS, Billings LK, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA. 2021;325(14):1403-1413. doi:10.1001/jama.2021.1831
29. Rubino DM, Greenway FL, Khalid U, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022;327(2):138-150. doi:10.1001/jama.2021.23619
30. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038