The Cardiovascular and Renal Effects of Glucagon-like Peptide 1 Receptor Agonists in Patients with Advanced Diabetic Kidney Disease

Overview

Journal Cardiovasc Diabetol

Publisher Biomed Central

Specialties Cardiology & Vascular Diseases
Endocrinology

Date 2023 Mar 18

PMID 36932379

Authors

Yuan Lin

Te-Hsiung Wang

Ming-Lung Tsai

Victor Chien-Chia Wu

Chin-Ju Tseng

Ming-Shyan Lin

Yan-Rong Li

Chih-Hsiang Chang

Tien-Shin Chou

Tzu-Hsien Tsai

Ning-I Yang

Ming-Jui Hung

Tien-Hsing Chen

Affiliations

Soon will be listed here.

Abstract

Background: To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m.

Methods: In this cohort study, patients with type 2 diabetes mellitus and eGFR < 30 mL/min per 1.73 m with a first prescription for GLP-1RAs or dipeptidyl peptidase 4 inhibitors (DPP-4is) from 2012 to 2021 (n = 125,392) were enrolled. A Cox proportional hazard model was used to assess the cardiorenal protective effects between the GLP-1RA and DDP-4i groups.

Results: A total of 8922 participants [mean (SD) age 68.4 (11.5) years; 4516 (50.6%) males; GLP-1RAs, n = 759; DPP-4is, n = 8163] were eligible for this study. During a mean follow-up of 2.1 years, 78 (13%) and 204 (13.8%) patients developed composite cardiovascular events in the GLP-1RA and DPP-4i groups, respectively [hazard ratio (HR) 0.88, 95% confidence interval CI 0.68-1.13]. Composite kidney events were reported in 134 (38.2%) and 393 (44.2%) patients in the GLP-1RA and DPP-4i groups, respectively (subdistribution HR 0.72, 95% CI 0.56-0.93).

Conclusions: GLP-1RAs had a neutral effect on the composite cardiovascular outcomes but reduced composite kidney events in the patients with advanced DKD compared with DPP-4is.

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References

Bloomgarden Z . The kidney and cardiovascular outcome trials. J Diabetes. 2017; 10(2):88-89. DOI: 10.1111/1753-0407.12616. View

Zheng S, Roddick A, Aghar-Jaffar R, Shun-Shin M, Francis D, Oliver N . Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis. JAMA. 2018; 319(15):1580-1591. PMC: 5933330. DOI: 10.1001/jama.2018.3024. View

Steven S, Hausding M, Kroller-Schon S, Mader M, Mikhed Y, Stamm P . Gliptin and GLP-1 analog treatment improves survival and vascular inflammation/dysfunction in animals with lipopolysaccharide-induced endotoxemia. Basic Res Cardiol. 2015; 110(2):6. DOI: 10.1007/s00395-015-0465-x. View

Jardine M, Hata J, Woodward M, Perkovic V, Ninomiya T, Arima H . Prediction of kidney-related outcomes in patients with type 2 diabetes. Am J Kidney Dis. 2012; 60(5):770-8. DOI: 10.1053/j.ajkd.2012.04.025. View

Husain M, Birkenfeld A, Donsmark M, Dungan K, Eliaschewitz F, Franco D . Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2019; 381(9):841-851. DOI: 10.1056/NEJMoa1901118. View

Almourani R, Chinnakotla B, Patel R, Kurukulasuriya L, Sowers J . Diabetes and Cardiovascular Disease: an Update. Curr Diab Rep. 2019; 19(12):161. DOI: 10.1007/s11892-019-1239-x. View

S Bailey T, Takacs R, Tinahones F, Rao P, Tsoukas G, Thomsen A . Efficacy and safety of switching from sitagliptin to liraglutide in subjects with type 2 diabetes (LIRA-SWITCH): a randomized, double-blind, double-dummy, active-controlled 26-week trial. Diabetes Obes Metab. 2016; 18(12):1191-1198. PMC: 5129465. DOI: 10.1111/dom.12736. View

Hviid A, Sorensen C . Glucagon-like peptide-1 receptors in the kidney: impact on renal autoregulation. Am J Physiol Renal Physiol. 2019; 318(2):F443-F454. DOI: 10.1152/ajprenal.00280.2019. View

Gonzalez-Perez A, Saez M, Vizcaya D, Lind M, Garcia Rodriguez L . Incidence and risk factors for mortality and end-stage renal disease in people with type 2 diabetes and diabetic kidney disease: a population-based cohort study in the UK. BMJ Open Diabetes Res Care. 2021; 9(1). PMC: 8491294. DOI: 10.1136/bmjdrc-2021-002146. View

10.

Ghoshal S, Freedman B . Mechanisms of Stroke in Patients with Chronic Kidney Disease. Am J Nephrol. 2019; 50(4):229-239. DOI: 10.1159/000502446. View

11.

Mazumder M, Paul R, Bhattacharya P, Borah A . Neurological sequel of chronic kidney disease: From diminished Acetylcholinesterase activity to mitochondrial dysfunctions, oxidative stress and inflammation in mice brain. Sci Rep. 2019; 9(1):3097. PMC: 6395638. DOI: 10.1038/s41598-018-37935-3. View

12.

Shao S, Chan Y, Kao Yang Y, Lin S, Hung M, Chien R . The Chang Gung Research Database-A multi-institutional electronic medical records database for real-world epidemiological studies in Taiwan. Pharmacoepidemiol Drug Saf. 2019; 28(5):593-600. DOI: 10.1002/pds.4713. View

13.

Nauck M, Weinstock R, Umpierrez G, Guerci B, Skrivanek Z, Milicevic Z . Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care. 2014; 37(8):2149-58. PMC: 4113177. DOI: 10.2337/dc13-2761. View

14.

Hernandez A, Green J, Janmohamed S, DAgostino Sr R, Granger C, Jones N . Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018; 392(10157):1519-1529. DOI: 10.1016/S0140-6736(18)32261-X. View

15.

Go A, Chertow G, Fan D, McCulloch C, Hsu C . Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351(13):1296-305. DOI: 10.1056/NEJMoa041031. View

16.

Muskiet M, Tonneijck L, Huang Y, Liu M, Saremi A, Heerspink H . Lixisenatide and renal outcomes in patients with type 2 diabetes and acute coronary syndrome: an exploratory analysis of the ELIXA randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2018; 6(11):859-869. DOI: 10.1016/S2213-8587(18)30268-7. View

17.

Tuttle K, Bakris G, Bilous R, Chiang J, de Boer I, Goldstein-Fuchs J . Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care. 2014; 37(10):2864-83. PMC: 4170131. DOI: 10.2337/dc14-1296. View

18.

Marso S, Bain S, Consoli A, Eliaschewitz F, Jodar E, Leiter L . Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016; 375(19):1834-1844. DOI: 10.1056/NEJMoa1607141. View

19.

Choi J, Kim S, Kwon S, Kim H, Jeon H . Renal Tubular Glucagon-Like Peptide-1 Receptor Expression Is Increased in Early Sepsis but Reduced in Chronic Kidney Disease and Sepsis-Induced Kidney Injury. Int J Mol Sci. 2019; 20(23). PMC: 6929157. DOI: 10.3390/ijms20236024. View

20.

Pratley R, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S . Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet. 2010; 375(9724):1447-56. DOI: 10.1016/S0140-6736(10)60307-8. View