Zhao Qian1, Sang Yafei1, Shang Lijing1, Ma Yujin2
1College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
2Department of Endocrinology and MeTableolism, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, China
Objective: To conduct a network meta-analysis to systematically evaluate the efficacy and safety of different doses of ertugliflozin in the treatment of Type 2 diabetes. Methods: The Pubmed, Embase, Cochrane library, CNKI, Wanfang, Weipu, CBM, Web of science and other daTableases were searched by computer from the beginning of the daTablease to 2021. To search for randomized controlled trial of different doses of ertugliflozin in the treatment of type 2 diabetes, to screen the literature according to inclusion and exclusion criteria, to extract data, and to evaluate the quality of the included studies by Cochrane systematic evaluation methods,using RevMan5.3 software and Stata 16.0 versions for analysis. RESULTS: A total of 11 randomized controlled trials (RCTs) were enrolled, including 5713 patients, The results of network meta-analysis showed that ertugliflozin 5,10,15,25 mg were superior to placebo in reducing glycosylated hemoglobin, Only 15 mg was statistically significant(p<0.05),and ertugliflozin 15 mg ranked first in the rank probability chart; 5,10,15 and 25 mg of ertugliflozin could reduce the fasting plasma glucose (FPG) in patients with type 2 diabetes Mellitus (T2D),and all had statistical significance(p<0.05),in the rank probability chart, ertugliflozin 10mg ranks first; Compared with the Placebo Group, ertugliflozin 5,10,15 and 25 mg reduced the weight of the patients, which was statistically significant(p<0.05). Ertugliflozin 10 mg ranked first in the rank probability chart; In the incidence of adverse drug reactions, hypoglycemia and discontinuation due to adverse drug reactions,compared with the placebo group, only 5 mg and 15 mg group had statistical significance(p<0.05), the difference was significant; The incidence of adverse drug reactions in ertugliflozin 15mg group was lower than that in 5mg group and the incidence of hypoglycemia was higher than that in 5mg group;The discontinuation rate of ertugliflozin 5mg group was higher than that in 15mg group,the difference was significant. But limited by the quality of the study, there is publication bias, and the conclusion still needs to be further verified by high-quality studies. Conclusion: The different dose groups of ertugliflozin are effective for the treatment of T2DM. 15 mg of ertugliflozin can significantly improve HbA1c, while the effect of 10 mg on FPG and body weight is more significant. But there are still certain security issues. Due to the limited quality of relevant literature, there is publication bias, and some dose-related literature is less included, and more large-sample, multi-center high-quality literature is still needed for verification.
Ertugliflozin; type 2 diabetes mellitus; efficacy; safety; network meta-analysis
Zhao Qian, Sang Yafei, Shang Lijing, Ma Yujin. A network meta-analysis of the effectiveness and safety of different doses of ertugliflozin in the treatment of type 2 diabetes. Frontiers in Medical Science Research (2021) Vol. 3 Issue 4: 34-42. https://doi.org/10.25236/FMSR.2021.030407.
 World Health Organization: Diabetes. https://www.who.int/news-room/fact-sheets/detail/diabetes. Accessed July 15, 2020.
 Pantalone KM, Misra-Hebert AD, Hobbs TM, et al. The probability of A1C goal attainment in patients with uncontrolled type 2 diabetes in a large integrated delivery system: a prediction model. Diabetes Care. 2020;43(8):1910–1919.https://doi.org/10.2337/dc19-0968.
 American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020. Diabetes Care. 2020; 43(Suppl. 1):S98–S110. https://doi.org/10.2337/dc20-S009.
 GIACCARIA, SORICEG, MUSCOGIURIG. Glucose toxicity: the leading actor in the pathogenesis and clinical history of type 2 diabetes-mechanisms and potentials for treatment[J]. Nutr MeTable Cardiovasc Dis, 2009, 19( 5) : 365-377.
 ROBERTSON R P,HARMON J,TRAN P O,et al. Glucose toxicity in beta-cells: type 2 diabetes,good radicals gone bad, and the glutathione connection[J]. Diabetes,2003,52 ( 3 ) : 581-587.
 HERMAN WH,PETERSEN M, KALYANI RR.Response to Comment on American Diabetes Asociation. Standards of Medical Care in Diabetes-2017[J]. Diabetes Care,2017,40(Suppl1):Sl-S135.
 HIGGINS JP, ALTMANDG, GOTZSCHE PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in ran- domised trials[J]. BMJ, 2011, 343 (182):d5928.
 CHENLX, LI YL, NINGGZ, et al. Comparative efficacy and tolerability of three treatments in old people with osteoporotic vertebral compression fracture: A network meta-analysis and systematic review [J]. PLOS One, 2015, 10(4):e0123153.
 Dagogo-Jack Samuel, Liu Jie, Eldor Roy, et al. Efficacy and safety of the addition of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sitagliptin: The VERTIS SITA2 placebo-controlled randomized study[J]. Diabetes Obes MeTable, 2018, 20: 530-540. PMID: 28921862.
 Ji Linong, Liu Yanmei, Miao Heng,et al. Safety and efficacy of ertugliflozin in Asian patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: VERTIS Asia. [2019-03-04]. https://publons.com/publon/10.1111/dom.13681.
 Terra Steven G, Focht Kristen, Davies Melanie, et al. Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone[J]. Diabetes Obes MeTable, 2017, 19: 721-728. PMID:28116776.
 Amin N B, Wang X, Jain S M, et al. Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin[J]. Diabetes Obes MeTable, 2015, 17: 591-598. PMID:25754396.
 Strojek Krzysztof, Pandey A Shekhar, Dell Vanessa, et al. Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV[J]. Diabetes Ther, 2021, 12: 1175-1192. PMID:33694093.
 Rosenstock Julio, Frias Juan, Páll Dénes, et al. Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET)[J]. Diabetes Obes MeTable, 2018, 20: 520-529. PMID: 28857451.
 Miller Sam, Krumins Tania, Zhou Haojin, et al. Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study[J]. Diabetes Ther, 2018, 9: 253-268. PMID:29313282.
 Hollander Priscilla, Liu Jie, Hill Julie, et al. Ertugliflozin Compared with Glimepiride in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin: The VERTIS SU Randomized Study[J]. Diabetes Ther, 2018, 9: 193-207. PMID:29282633.
 Grunberger George, Camp Sarah, Johnson Jeremy, et al. Ertugliflozin in Patients with Stage 3 Chronic Kidney Disease and Type 2 Diabetes Mellitus: The VERTIS RENAL Randomized Study[J]. Diabetes Ther, 2018, 9: 49-66. PMID:29159457.
 Pratley Richard E, Eldor Roy, Raji Annaswamy, et al. Ertugliflozin plus sitagliptin versus either individual agent over 52 weeks in patients with type 2 diabetes mellitus inadequately controlled with metformin: The VERTIS FACTORIAL randomized trial[J]. Diabetes Obes MeTable, 2018, 20: 1111-1120. PMID:29266675.
 Aronson Ronnie, Frias Juan, Goldman Allison, et al. Long-term efficacy and safety of ertugliflozin monotherapy in patients with inadequately controlled T2DM despite diet and exercise: VERTIS MONO extension study[J]. Diabetes Obes MeTable, 2018, 20: 1453-1460. PMID:29419917.
 Ertugliflozin for Type 2 Diabetes[J]. JAMA, 2018, 319: 2434-2435. PMID:29922825.