Meta‑analysis of the efficacy of liraglutide in patients with type 2 diabetes accompanied by incipient nephropathy

Liu,Wei; Yu,Jiangyi; Tian,Ting; Miao,Junjun; Shang,Wenbin

doi:10.3892/etm.2019.7577

Meta‑analysis of the efficacy of liraglutide in patients with type 2 diabetes accompanied by incipient nephropathy

Authors:
- Wei Liu
- Jiangyi Yu
- Ting Tian
- Junjun Miao
- Wenbin Shang
View Affiliations

Affiliations: Department of Endocrinology and Metabolism, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China, Department of Endocrinology and Metabolism, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
Published online on: May 13, 2019 https://doi.org/10.3892/etm.2019.7577
Pages: 342-351
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The efficacy of liraglutide in patients with type 2 diabetes accompanied by early‑stage nephropathy has remained to be fully elucidated. The present meta‑analysis was performed to determine the clinical outcomes associated with liraglutide treatment. The PubMed, Ovid, Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang databases were searched in October 2018 to identify randomized controlled trials of liraglutide for diabetes patients with early‑stage nephropathy. The treatment effect was estimated by calculating the mean difference (MD). Heterogeneity was assessed using χ2 and I2 tests. In addition, risk of bias graphs and summaries were used to assess the quality of the trials included. A total of 13 randomized controlled trials were included in the present meta‑analysis. In subjects with stage I‑II diabetic nephropathy (DN), liraglutide had obvious advantages in lowering the urinary albumin‑to‑creatinine ratio [UACR; MD=‑90.96, 95% confidence interval (CI)=‑94.12 to ‑87.80, P<0.00001], urinary albumin excretion rate (UAER; MD=‑64.86, 95% CI=‑66.63 to ‑63.08, P<0.00001), serum creatinine (Scr; MD=‑13.67, 95% CI=‑17.88 to ‑9.46, P<0.00001). In subjects with stage‑III DN, liraglutide had favorable effects on renal function (UACR: MD=‑11.23, 95% CI=‑13.14 to ‑9.32, P<0.00001; UAER: MD=‑14.06; 95% CI=‑6.93 to ‑11.18; P<0.00001; Scr: MD=‑9.17, 95% CI=‑14.61 to ‑3.72, P=0.0010) and exhibited anti‑inflammatory effects (transforming growth factor‑β1: P<0.00001; tumor necrosis factor‑α: P=0.006; interleukin‑6: P<0.00001). Furthermore, liraglutide also reduced the blood lipid levels, body mass index and post‑prandial blood glucose. The most common adverse effects of liraglutide were gastrointestinal tract reactions and hypoglycemia, but these symptoms resolved quickly. Liraglutide appears to be effective in reducing proteinuria, improving renal function, producing an anti‑inflammatory effect and ameliorating glucose and lipid metabolism in diabetic patients with early‑stage nephropathy.

View Figures

View References

1	Whiting DR, Guariguata L, Weil C and Shaw J: IDF Diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 94:311–321. 2011. View Article : Google Scholar : PubMed/NCBI
2	Tong L and Adler S: Glycemic control of type 2 diabetes mellitus across stages of renal impairment: Information for primary care providers. Postgrad Med. 130:381–393. 2018. View Article : Google Scholar : PubMed/NCBI
3	U.S. Food Drug Administration, . Drugs@FDA: FDA Approved Drug Products. VICTOZA (Liraglutide). http://www.accessdata.fda.gov/July 11–2016
4	Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B and Buse JB; LEADER Steering Committee and Investigators, : Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med. 377:839–848. 2017. View Article : Google Scholar : PubMed/NCBI
5	Davies MJ, Bain SC, Atkin SL, Rossing P, Scott D, Shamkhalova MS, Bosch-Traberg H, Syrén A and Umpierrez GE: Efficacy and safety of liraglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRA-RENAL): A randomized clinical trial. Diabetes Care. 39:222–230. 2016.PubMed/NCBI
6	Higgins JP, Thompson SG, Deeks JJ and Altman DG: Measuring inconsistency in meta-analyses. BMJ. 327:557–560. 2003. View Article : Google Scholar : PubMed/NCBI
7	Higgins JP and Green S: Cochrane handbook for systematic reviews of interventions version 5.1.2. The cochrane collaboration, 2011. http://handbook.cochrane.org/April 8–2018
8	Zhang JH, Liu XR, Sheng CX and Liu YE: Analysis on difference in gastrointestinal hormone levels of patients with the history of diabetes and concurrent nephropathy and study on the role of liraglutide. Eur Rev Med Pharmacol Sci. 21:3523–3529. 2017.PubMed/NCBI
9	Zha M, Zhang S, Ruan Y, Shi M, Zhou L and Huang LJ: Clinical effects of combination therapy of Huangkui capsules and liraglutide on patients with early diabetic nephropathy. Chin Trad Patent Med. 40:1493–1495. 2018.(In Chinese).
10	Dong L and Zhao JH: Effects of liraglutide on renal function in patients with microalbuminuria of diabetic nephropathy. Lin Chang Hui Cui. 33:420–423. 2018.
11	Li Q, Cao WJ, Zhou GY and Yang LH: Effects of liraglutide on early diabetic nephropathy and its relationship with the changes of VEGF and VEGF-A. Xiangnan Xue Yuan Xue Bao (Yi Xue Ban). 19:6–11. 2017.
12	Zheng Y and Yu SD: Clinical effects of combination therapy of insulin glargine and liraglutide on type 2 diabetic patients with nephropathy. Xiandai Shi Yong Yi Xue. 27:251–253. 2015.
13	Yang R, Wang YF and Zhang W: Liraglutide combined with low dosage telmisartan decreases the serum levels of TNF-α, IL-6 and TGF-β1 in patients with early diabetic nephropathy. Med J West China. 28:191–194. 2016.(In Chinese).
14	Shen YP, Qiao Q and Lu GY: Effect of liraglutide on PI3K-Akt-mTOR pathway in patients with diabetic nephropathy. Huazhong Ke Ji Da Xue Xue Bao (Yi Xue Ban). 46:466–470. 2017.
15	Chen ZP: Efficacy and safety analysis of Liraglutide in treatment of patients with type 2 diabetes mellitus and mild to moderate renal disease. Zhongguo Dang Dai Yi Yao. 23:131–133. 2016.
16	Ren W, Guo JJ, Zuo GX, Li YB, Gao LL, Li X and Liu J: Effects of liraglutide on early diabetic nephropathy with obese. Chin Remedies & Clinics. 15:1284–1286. 2015.(In Chinese).
17	Zhao CY, Guo HT, Dai HS, Tian JR and Zhao YQ: Clinical effects of liraglutide on early diabetic nephropathy. Shandong Yi Yao. 54:47–49. 2014.(In Chinese).
18	Aiyitan A and Qing Q: Clinical effect of liraglutide in treating early diabetic nephropathies and the influence of renal function and adipocytokines. Chin J Clin Rational Drug Use. 10:10–14. 2017.(In Chinese).
19	Liu R: Protective effect of hypoglycemic therapy by liraglutide on renal function in early diabetic nephropathy. J Hainan Med Univ. 22:43–46. 2016.
20	Liu CY: Liraglutide treatment efficacy of early type 2 diabetic nephropathy and its mechanism analysis. Dalian Yi Ke Da Xue. 9–11. 2015.
21	Fineberg D, Jandeleit-Dahm KA and Cooper ME: Diabetic nephropathy: Diagnosis and treatment. Nat Rev Endocrinol. 9:713–723. 2013. View Article : Google Scholar : PubMed/NCBI
22	Jorsal T, Rhee NA, Pedersen J, Wahlgren CD, Mortensen B, Jepsen SL, Jelsing J, Dalbøge LS, Vilmann P, Hassan H, et al: Enteroendocrine K and L cells in healthy and type 2 diabetic individuals. Diabetologia. 61:284–294. 2018. View Article : Google Scholar : PubMed/NCBI
23	Sonne DP, Rehfeld JF, Holst JJ, Vilsbøll T and Knop FK: Postprandial gallbladder emptying in patients with type 2 diabetes: Potential implications for bile-induced secretion of glucagon-like peptide 1. Eur J Endocrinol. 171:407–419. 2014. View Article : Google Scholar : PubMed/NCBI
24	Andersen A, Lund A, Knop FK and Vilsbøll T: Glucagon-like peptide 1 in health and disease. Nat Rev Endocrinol. 14:390–403. 2018. View Article : Google Scholar : PubMed/NCBI
25	Holst JJ: The physiology of glucagon-like peptide 1. Physiol Rev. 87:1409–1439. 2007. View Article : Google Scholar : PubMed/NCBI
26	Kreymann B, Williams G, Ghatei MA and Bloom SR: Glucagon-like peptide-1 7–36: A physiological incretin in man. Lancet. 2:1300–1304. 1987. View Article : Google Scholar : PubMed/NCBI
27	Lopez-Giacoman S and Madero M: Biomarkers in chronic kidney disease, from kidney function to kidney damage. World J Nephrol. 4:57–73. 2015. View Article : Google Scholar : PubMed/NCBI
28	Javanmardi M, Azadi NA, Amini S and Abdi M: Diagnostic value of cystatin C for diagnosis of early renal damages in type 2 diabetic mellitus patients: The first experience in Iran. J Res Med Sci. 20:571–576. 2015. View Article : Google Scholar : PubMed/NCBI
29	Zhou SJ, Bai L, Lv L, Chen R, Li CJ, Liu XY, Yu DM and Yu P: Liraglutide ameliorates renal injury in streptozotocin-induced diabetic rats by activating endothelial nitric oxide synthase activity via the downregulation of the nuclear factor-κB pathway. Mol Med Rep. 10:2587–2594. 2014. View Article : Google Scholar : PubMed/NCBI
30	Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, Zdravkovic M, Ravn GM and Simó R; Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group, : Liraglutide versus insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): A randomised controlled trial. Diabetologia. 52:2046–2055. 2009. View Article : Google Scholar : PubMed/NCBI