Objective To summarize the key evidence in the development of drug treatment strategies for type 2 diabetes mellitus (T2DM), and to provide an evidence-based roadmap for tailoring pharmacological strategies in patients with T2DM.

Methods  A systematic search of domestic and foreign databases, relevant guidelines websites, and T2DM guidelines and expert consensus organized by the society was conducted. The search time limit is from January 1, 2010, to April 1, 2024, and the update search is until April 1, 2025. A series of guidelines with early publication, stable and timely update, clear use process of antihyperglycemic drugs and high clinical applicability of the guidelines were screened.

Results  Two guideline series compiled by the Chinese Diabetes Society and the American Diabetes Association were selected to summarize the development of drug treatment strategies for T2DM, and to summarize the key evidence. With the version updates, the overall development trend of the two guideline series is consistent: both of them pay more attention to individualized treatment and comprehensive management, from blood glucose oriented to outcome oriented, and the dual benefits of GLP-1RA, SGLT2i and other drugs hypoglycemic+cardiorenal protection are the key to promoting change. However, the two series differ in the timing of addressing cardiac and renal complications and weight management. Differences also exist in the details of first-line agent selection and the prioritization of cardiac and renal complications.

Conclusion  This study summarizes the key evidence in the development of drug treatment strategies for T2DM, and to promote the rational planning of drug treatment strategies for patients with T2DM by medical staff.

1.World Health Organization. World health statistics 2023: monitoring health for the SDGs, sustainable development goals[R]. Geneva, Switzerland: World Health Organization, 2023.

2.International Diabetes Federation. Type 2 diabetes[EB/OL]. [2024-10-01]. https://idf.org/about-diabetes/diabetes-facts-figures/

3.Shah MS, Brownlee M. Molecular and cellular mechanisms of cardiovascular disorders in diabetes[J]. Circ Res, 2016, 118(11): 1808-1829.

4.Ye X, Yu R, Jiang F, et al. Osteocalcin and risks of incident diabetes and diabetic kidney disease: a 4.6-year prospective cohort study[J]. Diabetes Care, 2022, 45(4): 830-836.

5.UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)[J]. Lancet, 1998, 352(9131): 854-865.

6.肖建中. 二甲双胍的作用机制新进展[J]. 中华糖尿病杂志, 2024, 16(7): 735-739. [Xiao JZ. Update on the mechanisms of action of metformin[J]. Chinese Journal of Diabetes, 2024, 16(7): 735-739.]

7.Lyu W, Wang X, Xu Q, et al. Mechanisms and characteristics of sulfonylureas and glinides[J]. Curr Top Med Chem, 2020, 20(1): 37-56.

8.赵一璟, 王昆, 刘超. 噻唑烷二酮类药物临床实用价值和安全性的再认识[J]. 国际内分泌代谢杂志, 2019, 39(4): 236-240. [Zhao YJ, Wang K, Liu C. Reconsideration of the efficacy and safety of thiazolidinediones[J]. International Journal of Endocrinology and Metabolism, 2019, 39(4): 236-240.]

9.中国老年医学学会内分泌代谢分会, 吕肖锋, 陈莉丽. α糖苷酶抑制剂临床应用中国专家共识[J]. 中国糖尿病杂志, 2024, 32(2): 81-90. [Chinese Geriatrics Society, Endocrinology and Metabolism Branch, Lyu XF, Chen LL. Chinese expert consensus on the clinical application of α-glucosidase inhibitors[J]. Chinese Journal of Diabetes, 2024, 32(2): 81-90.]

10.Caruso I, Giorgino F. SGLT-2 inhibitors as cardio-renal protective agents[J]. Metabolism, 2022, 127: 154937.

11.Lee MMY, Sattar N, Pop-Busui R, et al. Cardiovascular and kidney outcomes and mortality with long-acting injectable and oral glucagon-like peptide 1 receptor agonists in individuals with type 2 diabetes: a systematic review and Meta-analysis of randomized trials[J]. Diabetes Care, 2025, 48(5): 846-859.

12.顾天伟, 朱大龙. 从2型糖尿病治疗理念的更新看胰高糖素样肽-1受体激动剂在中国指南中的地位变迁[J]. 中华糖尿病杂志, 2022, 14(11): 1128-1135. [Gu TW, Zhu DL. Evolving status of glucagon-like peptide-1 receptor agonist in Chinese guidelines from the perspective of updating treatment concept for type 2 diabetes mellitus[J]. Chinese Journal of Diabetes Mellitus, 2022, 14(11): 1128-1135.]

13.Nauck MA, Wefers J, Meier JJ. Treatment of type 2 diabetes: challenges, hopes, and anticipated successes[J]. Lancet Diabetes Endocrinol, 2021, 9(8): 525-544.

14.Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American association of clinical endocrinologists and american college of endocrinology on the comprehensive type 2 diabetes management algorithm-2019 executive summary[J]. Endocr Pract, 2019, 25(1): 69-101.

15.中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2010年版)[J]. 中国糖尿病杂志, 2012, 20(1): 81-117. [Chinese Diabetes Society. Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2010 edition)[J]. Chinese Journal of Diabetes, 2012, 20(1): 81-117.]

16.中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2013年版)[J]. 中华糖尿病杂志, 2014, 6(7): 447-498. [Chinese Diabetes Society. China guideline for type 2 diabetes mellitus (2013 edition)[J]. Chinese Journal of Diabetes, 2014, 6(7): 447-498.]

17.中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版) [J]. 中华糖尿病杂志, 2018, 10(1): 4-67. [Chinese Diabetes Society. Chinese guideline for the prevention and treatment of type 2 diabetes mellitus (2017 edition)[J]. Chinese Journal of Diabetes, 2018, 10(1): 4-67.]

18.中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版)[J]. 中华糖尿病杂志, 2021, 13(4): 315-409. [Chinese Diabetes Society. Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition)[J]. Chinese Journal of Diabetes, 2021, 13(4): 315-409.]

19.中华医学会糖尿病学分会. 中国糖尿病防治指南(2024版)[J]. 中华糖尿病杂志, 2025, 17(1): 16-139. [Chinese Diabetes Society. Guideline for the prevention and treatment of diabetes mellitus in China (2024 edition)[J]. Chinese Journal of Diabetes, 2025, 17(1): 16-139.]

20.American Diabetes Association. Standards of medical care in diabetes--2014[J]. Diabetes Care, 2014, 37(1): S14-S80.

21.American Diabetes Association. Approaches to glycemic treatment[J]. Diabetes Care, 2015, 38(1): S41-S48.

22.American Diabetes Association. Approaches to glycemic treatment[J]. Diabetes Care, 2016, 39(1): S52-S59.

23.American Diabetes Association. Pharmacologic approaches to glycemic treatment[J]. Diabetes Care, 2017, 40(1): S64-S74.

24.American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2018[J]. Diabetes Care, 2018, 41(1): S73-S85.

25.American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2019[J]. Diabetes Care, 2019, 42(1): S90-S102.

26.American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020[J]. Diabetes Care, 2020, 43(1): S98-S110.

27.American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2021[J]. Diabetes Care, 2021, 44(1): S111-S124.

28.American Diabetes Association Professional Practice Committee. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2022[J]. Diabetes Care, 2022, 45(1): S125-S143.

29.American Diabetes Association Professional Practice Committee. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2023[J]. Diabetes Care, 2023, 46(1): S140-S157.

30.American Diabetes Association Professional Practice Committee. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2024[J]. Diabetes Care, 2024, 47(1): S158-S178.

31.American Diabetes Association Professional Practice Committee. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2025[J]. Diabetes care, 2025, 48(1): 181-206.

32.Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes[J]. N Engl J Med, 2008, 359(15): 1577-1589.

33.Adler AI, Coleman RL, Leal J, et al. Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91)[J]. Lancet, 2024, 404(10448): 145-155.

34.李焱. 降糖与糖尿病大血管病变关系的争鸣与思考[J]. 中华糖尿病杂志, 2020, 12(11): 861-864. [Li Y. Discussion on the relationship between hypoglycemic and diabetic macrovascular disease[J]. Chinese Journal of Diabetes, 2020, 12(11): 861-864.]

35.Kivimaki M, Strandberg T, Pentti J, et al. Body-mass index and risk of obesity-related complex multimorbidity: an observational multicohort study[J]. Lancet Diabetes Endocrinol, 2022, 10(4): 253-263.

36.Lingvay I, Sumithran P, Cohen RV, et al. Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation[J]. Lancet, 2022, 399(10322): 394-405.

37.Kim K, Hong S, Han K, et al. Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study[J]. BMJ, 2024, 384: e76388.

38.《二甲双胍临床应用专家共识》更新专家组. 二甲双胍临床应用专家共识(2023年版)[J]. 中华内科杂志, 2023, 62(6): 619-630. [Expert Group for Updating Chinese Expert Consensus on Metformin in Clinical Practice. Chinese expert consensus on metformin in clinical practice: 2023 update[J]. Chinese Journal of Internal Medicine, 2023, 62(6): 619-630.]

39.Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes[J]. N Engl J Med, 2015, 373(22): 2117-2128.

40.Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes[J]. N Engl J Med, 2017, 377(7): 644-657.

41.Sorli C, Harashima SI, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial[J]. Lancet Diabetes Endocrinol, 2017, 5(4): 251-260.

42.Cannon CP, Pratley R, Dagogo-Jack S, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes[J]. N Engl J Med, 2020, 383(15): 1425-1435.

43.McMurray J, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction[J]. N Engl J Med, 2019, 381(21): 1995-2008.

44.Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure[J]. N Engl J Med, 2020, 383(15): 1413-1424.

45.Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction[J]. N Engl J Med, 2021, 385(16): 1451-1461.

46.Solomon SD, McMurray J, Claggett B, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction[J]. N Engl J Med, 2022, 387(12): 1089-1098.

47.Heerspink H, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease[J]. N Engl J Med, 2020, 383(15): 1436-1446.

48.Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy[J]. N Engl J Med, 2019, 380(24): 2295-2306.

49.Ahren B, Masmiquel L, Kumar H, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial[J]. Lancet Diabetes Endocrinol, 2017, 5(5): 341-354.

50.Pratley R, Amod A, Hoff ST, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial[J]. Lancet, 2019, 394(10192): 39-50.

51.Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes[J]. N Engl J Med, 2021, 385(6): 503-515.

52.Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes[J]. N Engl J Med, 2016, 375(4): 311-322.

53.Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes[J]. N Engl J Med, 2016, 375(19): 1834-1844.

54.Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes[J]. N Engl J Med, 2017, 377(13): 1228-1239.

55.Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (harmony outcomes): a double-blind, randomised placebo-controlled trial[J]. Lancet, 2018, 392(10157): 1519-1529.

56.Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial[J]. Lancet, 2019, 394(10193): 121-130.

57.Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes[J]. N Engl J Med, 2024, 391(2): 109-121.

58.Guo W, Tian W, Lin L, et al. Liraglutide or insulin glargine treatments improves hepatic fat in obese patients with type 2 diabetes and nonalcoholic fatty liver disease in twenty-six weeks: a randomized placebo-controlled trial[J]. Diabetes Res Clin Pract, 2020, 170: 108487.

59.Flint A, Andersen G, Hockings P, et al. Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging[J]. Aliment Pharmacol Ther, 2021, 54(9): 1150-1161.

60.Loomba R, Hartman ML, Lawitz EJ, et al. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis[J]. N Engl J Med, 2024, 391(4): 299-310.

61.Lawitz EJ, Fraessdorf M, Neff GW, et al. Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis[J]. J Hepatol, 2024, 81(5): 837-846.

62.Sanyal AJ, Bedossa P, Fraessdorf M, et al. A phase 2 randomized trial of survodutide in MASH and fibrosis[J]. N Engl J Med, 2024, 391(4): 311-319.

63.Targher G, Mantovani A, Byrne CD. Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease[J]. Lancet Gastroenterol Hepatol, 2023, 8(2): 179-191.

64.邢颖, 刘红萍, 文天才. 糖尿病个性化治疗临床决策支持系统的研究进展[J]. 中华糖尿病杂志, 2022, 14(8): 865-868. [Xing  Y, Liu  HP, Wen TC. Research progress of clinical decision support system for personalized diabetes mellitus[J]. Chinese Journal of Diabetes, 2022, 14(8): 865-868.]

65.杨立勇. 降糖药物的心血管获益评价: 温故而知新[J]. 中华糖尿病杂志, 2019, 11(12): 769-773. [Yang LY. Cardiovascular benefit of antidiabetic drugs: gain new knowledge by reviewing old[J]. Chinese Journal of Diabetes, 2019, 11(12): 769-773.]

66.任婧, 肖新华. 对钠-葡萄糖共转运蛋白2抑制剂获益机制的再认识[J]. 中华糖尿病杂志, 2023, 15(7): 656-661. [Ren J, Xiao XH. Rethinking of sodium-glucose cotransporter 2 inhibitor mechanism[J]. Chinese Journal of Diabetes, 2023, 15(7): 656-661.]

67.Kristensen SL, Rorth 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[J]. Lancet Diabetes Endocrinol, 2019, 7(10): 776-785.

68.杨光燃. 新型降糖药物对2型糖尿病患者的肾脏获益及应用前景 [J]. 中国全科医学, 2021, 24(18): 2245-2250. [Yang GR. Application prospect and renal outcomes of novel antidiabetic agents in patients with type 2 diabetes[J]. Chinese General Practice, 2021, 24(18): 2245-2250.]

69.Diamant M, Van Gaal L, Stranks S, et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial[J]. Lancet, 2010, 375(9733): 2234-2243.

70.Davies M, Heller S, Sreenan S, et al. Once-weekly exenatide versus once- or twice-daily insulin detemir: randomized, open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in combination with sulfonylureas[J]. Diabetes Care, 2013, 36(5): 1368-1376.

71.Giorgino F, Benroubi M, Sun JH, et al. Efficacy and safety of once-weekly dulaglutide versus insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD-2)[J]. Diabetes Care, 2015, 38(12): 2241-2249.

72.Singh S, Wright EJ, Kwan AY, et al. Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and Meta-analysis[J]. Diabetes Obes Metab, 2017, 19(2): 228-238.

73.Levin PA, Nguyen H, Wittbrodt ET, et al. Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research[J]. Diabetes Metab Syndr Obes, 2017, 10: 123-139.

74.Abd El Aziz MS, Kahle M, Meier JJ, et al. A Meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients[J]. Diabetes Obes Metab, 2017, 19(2): 216-227.

75.Aroda VR, Bain SC, Cariou B, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial[J]. Lancet Diabetes Endocrinol, 2017, 5(5): 355-366.

76.Del PS, Kahn SE, Pavo I, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial[J]. Lancet, 2021, 398(10313): 1811-1824.

77.Vasishta S, Ganesh K, Umakanth S, et al. Ethnic disparities attributed to the manifestation in and response to type 2 diabetes: insights from metabolomics[J]. Metabolomics, 2022, 18(7): 45.