Objective  To evaluate the efficacy, safety and cost-effectiveness of ertugliflozin in the treatment of type 2 diabetes mellitus by rapid health technology assessment to provide a basis for clinical decision-making.

Methods  PubMed, Embase, the Cochrane Library, CNKI, WanFang Data, VIP database and health technology assessment (HTA) related websites and databases were searched from the inception date to January 2024. Two researchers independently screened the literature, extracted the data, assessed the quality and carried out the qualitative analysis.

Results  A total of 27 articles were included, in which 2 HTA reports, 24 systematic reviews/meta-analyses and 2 pharmacoeconomic studies. Compared with placebo, ertugliflozin could significantly lower hemoglobin A1c level, fasting plasma glucose, hospitalization for heart failure, body weight and blood pressure levels, but there were no significant difference in all-cause mortality, cardiovascular mortality and composite renal outcome. In terms of safety, there were no significant difference in the risk of urinary tract infections, fracture, amputation and symptomatic hypoglycemia between ertugliflozin and placebo or other hypoglycemic drugs. However, ertugliflozin increased the risk of ketoacidosis, genital mycotic infections and lowered of estimated glomerular filtration rate. Pharmacoeconomic studies showed that ertugliflozin had better cost-utility and cost-effectiveness in type 2 diabetes in China.

Conclusion  Ertugliflozin is effective and safety in treating type 2 diabetes mellitus, but it’s necessary to carry out the head to head studies among efficacy, safety and economics research  in China.

1.Coles B, Zaccardi F, Ling S, et al. Cardiovascular events and mortality in people with and without type 2 diabetes: An observational study in a contemporary multi-ethnic population[J]. J Diabetes Investig, 2021, 12(7): 1175-1182. DOI: 10.1111/jdi.13464.

2.Drozd M, Pujades-Rodriguez M, Sun F, et al. Causes of death in people with cardiovascular disease: a UK Biobank Cohort Study[J]. J Am Heart Assoc, 2021, 10(22): e023188. DOI: 10.1161/JAHA.121.023188.

3.Marx N, Federici M, Schütt K, et al. 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes[J]. Eur Heart J, 2023, 44(39): 4043-4140. DOI: 10.1093/eurheartj/ehad192.

4.中华医学会糖尿病学分会, 国家基层糖尿病防治管理办公室. 国家基层糖尿病防治管理指南(2022)[J]. 中华内科杂志, 2022, 61(3): 249-262. DOI: 10.3760/cma.j.cn112138-20220120-000063.

5.American Diabetes Association Professional Practice Committee. Pharmacologic approaches to glycemic treatment: standards of care in Diabetes-2024[J]. Diabetes Care, 2024, 47(Suppl 1): S158-S178. DOI: 10.2337/dc24-S009.

6.Canadian Agency for Drugs and Technologies in Health. CADTH Canadian Drug Expert  Committee Recommendation: ERTUGLIFLOZIN[EB/OL]. (2019-01-25) [2024-1-12].错误!超链接引用无效。.

7.National Institute for Health and Care Excellence. Ertugliflozin as monotherapy or with metformin for treating type 2 diabetes[EB/OL]. (2019-02) [2024-1-12]. https://www.nice.org.uk/ guidance/ta572/documents/final-appraisal-determination-document.

8.INAHTA. A checklist for health technology assessment reports[EB/OL]. (2007) [2024-2-10]. https://www.inahta.org/wp-content/uploads/2014/04/INAHTA_HTA_Checklist_English.pdf.

9.葛龙, 潘蓓, 潘佳雪, 等. 解读AMSTAR-2基于随机和(或)非随机对照试验系统评价的质量评价工具[J]. 中国药物评价, 2017, 34(5): 334-338. [Ge L, Pan B, Pan JX, et al. An introduction of AMSTAR-2: a quality assessment instrument of systematic reviews including randomized or non-randomized controlled trials or both[J]. Chinese Journal of Drug Evaluation, 2017, 34(5): 334-338.] DOI: 10.3969/j.issn.2095-3593.2017.05.005.

10.ISPOR. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 Resources[EB/OL]. (2022) [2024-2-10]. https://www.ispor.org/heor-resources/good-practices/cheers.

11.Tian L, Ai S, Zheng H, et al. Cardiovascular and renal outcomes with sodium glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus: a system review and network meta-analysis[J]. Front Pharmacol, 2022, 13:986186. DOI: 10.3389/fphar.2022.986186.

12.Kongmalai T, Hadnorntun P, Leelahavarong P, et al. Comparative cardiovascular benefits of individual SGLT2 inhibitors in type 2 diabetes and heart failure: a systematic review and network meta-analysis of randomized controlled trials[J]. Front Endocrinol (Lausanne), 2023, 14: 1216160. DOI: 10.3389/fendo.2023.1216160.

13.Tsapas A, Avgerinos I, Karagiannis T, et al. Comparative effectiveness of glucose-lowering drugs for type 2 diabetes: a systematic review and network meta-analysis[J]. Ann Intern Med, 2020, 173(4): 278-286. DOI: 10.7326/M20-0864.

14.Täger T, Atar D, Agewall S, et al. Comparative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for cardiovascular outcomes in type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials[J]. Heart Fail Rev, 2021, 26(6): 1421-1435. DOI: 10.1007/s10741-020-09954-8.

15.Li CX, Liu LY, Zhang CX, et al. Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials[J]. Front Endocrinol (Lausanne), 2023, 14: 1238399. DOI: 10.3389/fendo.2023.1238399.

16.Chen L, Xue Q, Yan C, et al. Comparative safety of different recommended doses of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials[J]. Front Endocrinol (Lausanne), 2023, 14: 1256548. DOI: 10.3389/fendo.2023.1256548.

17.Wang M, Zhang X, Ni T, et al. Comparison of new oral hypoglycemic agents on risk of urinary tract and genital infections in type 2 diabetes: a network meta-analysis[J]. Adv Ther, 2021, 38(6): 2840-2853. DOI: 10.1007/s12325-021-01759-x.

18.Donnan JR, Grandy CA, Chibrikov E, et al. Dose response of sodium glucose cotransporter-2 inhibitors in relation to urinary tract infections: a systematic review and network meta-analysis of randomized controlled trials[J]. CMAJ Open, 2018, 6(4): E594-E602. DOI: 10.9778/cmajo.20180111.

19.Cheng Q, Zou S, Feng C, et al. Effect of ertugliflozin on renal function and cardiovascular outcomes in patients with type 2 diabetes mellitus: a systematic review and meta-analysis[J]. Medicine (Baltimore), 2023, 102(10): e33198. DOI: 10.1097/MD.0000000000033198.

20.Zhang YS, Zheng YD, Yuan Y, et al. Effects of anti-diabetic drugs on fracture risk: a systematic review and network meta-analysis[J]. Front Endocrinol (Lausanne), 2021, 12: 735824. DOI: 10.3389/fendo.2021.735824.

21.Liu L, Shi FH, Xu H, et al. Efficacy and safety of ertugliflozin in type 2 diabetes: a systematic review and meta-analysis[J]. Front Pharmacol, 2022, 12: 752440. DOI: 10.33 89/fphar.2021.752440.

22.McNeill AM, Davies G, Kruger E, et al. Ertugliflozin compared to other anti-hyperglycemic agents as monotherapy and add-on therapy in type 2 diabetes: a systematic literature review and network meta-analysis[J]. Diabetes Ther, 2019, 10(2): 473-491. DOI: 10.1007/s13300-019-0566-x.

23.Zaman M, Memon RS, Amjad A, et al. Effect of ertugliflozin on glycemic levels, blood pressure and body weight of patients with type 2 diabetes mellitus: a systematic review and meta-analysis[J]. J Diabetes Metab Disord, 2020, 19(2): 1873-1878. DOI: 10.1007/s40200-020-00623-z.

24.Zhang F, Wang W, Hou X. Effectiveness and safety of ertugliflozin for type 2 diabetes: a meta-analysis of data from randomized controlled trials[J]. J Diabetes Investig, 2022, 13(3): 478-488. DOI: 10.1111/jdi.13688.

25.Khan P, Venkatesh S, Parveen R, et al. Longitudinal efficacy of ertugliflozin in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials[J]. Expert Opin Pharmacother, 2023, 24(18): 2199-2210. DOI: 10.1080/14656566.2023.2279100.

26.Sridharan K, Sivaramakrishnan G. Risk of diabetic ketoacidosis associated with sodium glucose cotransporter-2 inhibitors: a network meta-analysis and meta-regression[J]. J Clin Med, 2024, 13(6): 1748. DOI: 10.3390/jcm13061748.

27.Huang J, Xiong S, Ding S, et al. Safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with conventional therapy at different periods: a meta-analysis of randomized controlled trials[J]. J Diabetes Res, 2020, 2020:9704659. DOI: 10.1155/2020/9704659.

28.田丽, 王琼英, 孙润民, 等. SGLT2i对2型糖尿病合并高血压患者24 h动态血压影响的荟萃分析[J]. 中华心血管病杂志, 2021, 49(10): 1000-1011.[Tian L, Wang QY, Sun RM, et al. Effects of SGLT2i on 24-hour ambulatory blood pressure in patients with type 2 diabetes complicating hypertension: a meta-analysis[J]. Chinese Journal of Cardiology, 2021, 49(10): 1000-1011.] DOI: 10.3760/cma.j.cn112148-20210127-00098.

29.Odutayo A, da Costa BR, Pereira TV, et al. Sodium-glucose cotransporter 2 inhibitors, all-cause mortality, and cardiovascular outcomes in adults with type 2 diabetes: a Bayesian meta-analysis and meta-regression[J]. J Am Heart Assoc, 2021, 10(18): e019918. DOI: 10.1161/JAHA.120.019918.

30.刘凤琪, 柴三葆, 赵厚宇, 等. 钠-葡萄糖共转运蛋白2抑制剂引起2型糖尿病患者尿路或生殖器感染风险的网状Meta分析[J]. 中华糖尿病杂志, 2022, 14(8): 799-808. [Liu FQ, Chai SB, Zhao HY, et al. Sodium-glucose cotransporter 2 inhibitors and the risk of urinary tract infections or genital infections in adult patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized controlled trials[J]. Chinese Journal of Diabetes, 2022, 14(8): 799-808.] DOI: 10.3760/cma.j.cn115791-20211217-00668.

31.赖彦岚, 黄爱文, 陈官旭, 等. SGLT-2抑制剂及GLP-1受体激动剂治疗2型糖尿病的心血管获益: 一项系统回顾和网状Meta分析[J]. 药学实践杂志, 2022, 40(4): 354-358. [Lai YL, Huang AW, Chen GX, et al. Cardiovascular benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in type 2 diabetes: a systematic review and network meta-analysis[J]. Journal of Pharmaceutical and Service, 2022, 40(4): 354-358.] DOI: 10.12206/j.issn.1006-0111.202109 108.

32.倪倩, 李婷, 裴艺芳, 等. 埃格列净单药治疗2型糖尿病安全性的Meta分析[J]. 中国药学杂志, 2019, 54(15): 1268-1275. [Ni Q, Li T, Pei YF, et al. Safety of ertugliflozin as a monotherapy for the treatment of type Ⅱ diabetes: a meta-analysis[J]. Chinese Pharmaceutical Journal, 2019, 54(15): 1268-1275.] DOI: 10.11669/cpj.2019.15.015.

33.邓慧远, 孔文强, 周义录, 等. 艾格列净治疗2型糖尿病疗效与安全性的系统评价和Meta分析[J]. 药物流行病学杂志, 2020, 29(12): 801-808. [Deng HY, Kong WQ, Zhou YL, et al. Efficacy and safety of ertugliflozin in the treatment of type 2 diabetes:a systematic review and meta-analysis[J]. Chinese Journal of Pharmacoepidemiology, 2020, 29(12): 801-808.] DOI: 10.19960/j.cnki.issn1005-0698.2020.12.001.

34.王声祥, 卢姗, 卢丹丹, 等. 西格列汀联合艾托格列净治疗2型糖尿病有效性和安全性的Meta分析[J]. 沈阳药科大学学报, 2022, 39(5): 583-590. [Wang SX, Lu S, Lu DD, et al. Efficacy and safety of sitagliptin plus ertugliflozin as combination therapy for type 2 diabetes:a meta-analysis[J]. Journal of Shenyang Pharmaceutical University, 2022, 39(5): 583-590.] DOI: 10.14066/j.cnki.cn21-1349/r.2022.0289.

35.颜建周, 龚小玲, 王媛, 等. 艾托格列净治疗中国2型糖尿病的成本-效用分析[J]. 中国药物经济学, 2021, 16(12): 11-21. [Yan JZ, Gong XL, Wang Y, et al. Cost-utility analysis of ertugliflozin for the treatment of type 2 diabetes in China[J]. China Journal of Pharmaceutical Economics, 2021, 16(12): 11-21] DOI: 10.12010/j.issn.1673-5846.2021.12.002.