Effects of novel hypoglycemic drugs on cardiovascular outcomes in patients with type 2 diabetes mellitus and its possible mechanism_West China Medical Journal

Authors：

SHI Yong ^1,2 ,  PENG Yong ¹

1. Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Geriatric Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (Affiliated Hosipital of University of Electronic Science and Technology of China), Chengdu, Sichuan 610072, P. R. China;

Corresponding author：

PENG Yong, Email: pengyong@scu.edu.cn

Keywords：

Novel hypoglycemic drug; cardiovascular outcome; sodium-glucose linked transporter 2 inhibitor; glucagon-like peptide-1 receptor agonist; dipeptidyl peptidase-4 inhibitor

DOI：

10.7507/1002-0179.202502006

Video：

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Abstract Full text Figures/Tables Video References Cited by

The risk of cardiovascular disease in patients with type 2 diabetes mellitus is significantly increased, which is the primary cause of death. Recent studies have shown that novel hypoglycemic drugs such as sodium-glucose linked transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have been proven to have cardiovascular protective effects through cardiovascular outcome trials. This article reviews the improvement effects of these drugs on cardiovascular outcomes and explores their possible mechanisms, such as improving myocardial metabolism and reducing inflammatory reactions, providing a reference for optimizing hypoglycemic regimens.

Citation： SHI Yong, PENG Yong. Effects of novel hypoglycemic drugs on cardiovascular outcomes in patients with type 2 diabetes mellitus and its possible mechanism. West China Medical Journal, 2025, 40(7): 1176-1181. doi: 10.7507/1002-0179.202502006 Copy

1.	Salehi B, Ata A, V Anil Kumar N, et al. Antidiabetic potential of medicinal plants and their active components. Biomolecules, 2019, 9(10): 551.
2.	Siasos G, Paschou SA, Tousoulis D. Mitochondria and diabetes. Ann Transl Med, 2020, 8(6): 262.
3.	Ambrosini S, Mohammed SA, Lüscher TF, et al. New mechanisms of vascular dysfunction in cardiometabolic patients: focus on epigenetics. High Blood Press Cardiovasc Prev, 2020, 27(5): 363-371.
4.	Siasos G, Skotsimara G, Oikonomou E, et al. Antithrombotic treatment in diabetes mellitus: a review of the literature about antiplatelet and anticoagulation strategies used for diabetic patients in primary and secondary prevention. Curr Pharm Des, 2020, 26(23): 2780-2788.
5.	Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med, 2008, 358(24): 2545-2559.
6.	Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med, 2007, 356(24): 2457-2471.
7.	Nat Rev Drug Discov. Regulatory watch: FDA issues guidance for cardiovascular risk assessment of novel antidiabetic agents. Nat Rev Drug Discov, 2009, 8(2): 99.
8.	Einhorn D. Treatment of glycemic control in diabetes in the CVOT era. J Diabetes, 2020, 12(1): 4.
9.	Van der Schueren B, Vrijlandt P, Thomson A, et al. New guideline of the European Medicines Agency (EMA) on the clinical investigation of medicinal products in the treatment and prevention of diabetes mellitus. Diabetologia, 2024, 67(7): 1159-1162.
10.	Nathan DM. Finding new treatments for diabetes--how many, how fast. . how good?. N Engl J Med, 2007, 356(5): 437-440.
11.	Dicker D. DPP-4 inhibitors: impact on glycemic control and cardiovascular risk factors. Diabetes Care, 2011, 34(Suppl 2): S276-S278.
12.	Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med, 2013, 369(14): 1317-1326.
13.	Heller SR, Bergenstal RM, White WB, et al. Relationship of glycated haemoglobin and reported hypoglycaemia to cardiovascular outcomes in patients with type 2 diabetes and recent acute coronary syndrome events: the EXAMINE trial. Diabetes Obes Metab, 2017, 19(5): 664-671.
14.	Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2015, 373(3): 232-242.
15.	Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA, 2019, 321(1): 69-79.
16.	Rosenstock J, Kahn SE, Johansen OE, et al. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial. JAMA, 2019, 322(12): 1155-1166.
17.	Cimmaruta D, Maiorino MI, Scavone C, et al. Efficacy and safety of insulin-GLP-1 receptor agonists combination in type 2 diabetes mellitus: a systematic review. Expert Opin Drug Saf, 2016, 15(2): 77-83.
18.	Bunck MC, Cornér A, Eliasson B, et al. Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care, 2011, 34(9): 2041-2047.
19.	Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2016, 375(4): 311-322.
20.	Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med, 2016, 375(19): 1834-1844.
21.	Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med, 2019, 381(9): 841-851.
22.	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. Lancet, 2018, 392(10157): 1519-1529.
23.	Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet, 2019, 394(10193): 121-130.
24.	Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med, 2015, 373(23): 2247-2257.
25.	Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2017, 377(13): 1228-1239.
26.	Del Prato S, 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. Lancet, 2021, 398(10313): 1811-1824.
27.	Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med, 2015, 373(22): 2117-2128.
28.	Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med, 2017, 377(7): 644-657.
29.	Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2019, 380(4): 347-357.
30.	Bloomgarden Z. The kidney and cardiovascular outcome trials. J Diabetes, 2018, 10(2): 88-89.
31.	Jia G, Sowers JR. Hypertension in diabetes: an update of basic mechanisms and clinical disease. Hypertension, 2021, 78(5): 1197-1205.
32.	Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia, 2017, 60(2): 215-225.
33.	Briasoulis A, Al Dhaybi O, Bakris GL. SGLT2 inhibitors and mechanisms of hypertension. Curr Cardiol Rep, 2018, 20(1): 1.
34.	Cruickshank K, Riste L, Anderson SG, et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function?. Circulation, 2002, 106(16): 2085-2090.
35.	Viazzi F, Bonino B, Mirijello A, et al. Long-term blood pressure variability and development of chronic kidney disease in type 2 diabetes. J Hypertens, 2019, 37(4): 805-813.
36.	Gupta R, Maitz T, Egeler D, et al. SGLT2 inhibitors in hypertension: role beyond diabetes and heart failure. Trends Cardiovasc Med, 2023, 33(8): 479-486.
37.	Gupta V, Canovatchel W, Lokesh BN, et al. Sodium-glucose cotransporter-2 inhibitors: moving beyond the glycemic treatment goal. Indian J Endocrinol Metab, 2017, 21(6): 909-918.
38.	Wang B, Zhong J, Lin H, et al. Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: a meta-analysis of clinical trials. Diabetes Obes Metab, 2013, 15(8): 737-749.
39.	Filippatos T, Tsimihodimos V, Pappa E, et al. Pathophysiology of diabetic dyslipidaemia. Curr Vasc Pharmacol, 2017, 15(6): 566-575.
40.	Vergès B. Pathophysiology of diabetic dyslipidaemia: where are we?. Diabetologia, 2015, 58(5): 886-899.
41.	Soran H, Schofield JD, Adam S, et al. Diabetic dyslipidaemia. Curr Opin Lipidol, 2016, 27(4): 313-322.
42.	Ståhlman M, Pham HT, Adiels M, et al. Clinical dyslipidaemia is associated with changes in the lipid composition and inflammatory properties of apolipoprotein-B-containing lipoproteins from women with type 2 diabetes. Diabetologia, 2012, 55(4): 1156-1166.
43.	Yaribeygi H, Maleki M, Reiner Ž, et al. Mechanistic view on the effects of SGLT2 inhibitors on lipid metabolism in diabetic milieu. J Clin Med, 2022, 11(21): 6544.
44.	Ejiri K, Miyoshi T, Kihara H, et al. Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure. Sci Rep, 2022, 12(1): 15449.
45.	Shi FH, Li H, Shen L, et al. High-dose sodium-glucose co-transporter-2 inhibitors are superior in type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab, 2021, 23(9): 2125-2136.
46.	Briand F, Mayoux E, Brousseau E, et al. Empagliflozin, via switching metabolism toward lipid utilization, moderately increases ldl cholesterol levels through reduced ldl catabolism. Diabetes, 2016, 65(7): 2032-2038.
47.	Andrikou E, Tsioufis C, Andrikou I, et al. GLP-1 receptor agonists and cardiovascular outcome trials: an update. Hellenic J Cardiol, 2019, 60(6): 347-351.
48.	Iorga RA, Bacalbasa N, Carsote M, et al. Metabolic and cardiovascular benefits of GLP-1 agonists, besides the hypoglycemic effect (review). Exp Ther Med, 2020, 20(3): 2396-2400.
49.	Stemmer K, Finan B, DiMarchi RD, et al. Insights into incretin-based therapies for treatment of diabetic dyslipidemia. Adv Drug Deliv Rev, 2020, 159: 34-53.
50.	Jialal I, Chaudhuri A. Targeting inflammation to reduce ASCVD in type 2 diabetes. J Diabetes Complications, 2019, 33(1): 1-3.
51.	Sato T, Aizawa Y, Yuasa S, et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol, 2018, 17(1): 6.
52.	Xu L, Nagata N, Nagashimada M, et al. SGLT2 inhibition by empagliflozin promotes fat utilization and browning and attenuates inflammation and insulin resistance by polarizing M2 macrophages in diet-induced obese mice. EBioMedicine, 2017, 20: 137-149.
53.	Salim HM, Fukuda D, Yagi S, et al. Glycemic control with ipragliflozin, a novel selective SGLT2 inhibitor, ameliorated endothelial dysfunction in streptozotocin-induced diabetic mouse. Front Cardiovasc Med, 2016, 3: 43.
54.	Dai M, Jia Z, Wang H, et al. Sodium-glucose cotransporter 2 inhibitor ameliorate angiotensin ii-induced hypertension and vascular injury by upregulating FGF21. Inflammation, 2025: 14.
55.	Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol, 2020, 17(12): 761-772.
56.	Wu Q, Yao Q, Hu T, et al. Dapagliflozin protects against chronic heart failure in mice by inhibiting macrophage-mediated inflammation, independent of SGLT2. Cell Rep Med, 2023, 4(12): 101334.
57.	Wong CK, McLean BA, Baggio LL, et al. Central glucagon-like peptide 1 receptor activation inhibits toll-like receptor agonist-induced inflammation. Cell Metab, 2024, 36(1): 130-143.e5.
58.	American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of care in diabetes-2025. Diabetes Care, 2025, 48(Suppl 1): S207-S238.
59.	Marx N, Federici M, Schütt K, et al. 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J, 2023, 44(39): 4043-4140.
60.	中华医学会糖尿病学分会. 中国糖尿病防治指南(2024 版). 中华糖尿病杂志, 2025, 17(1): 16-139.

1. Salehi B, Ata A, V Anil Kumar N, et al. Antidiabetic potential of medicinal plants and their active components. Biomolecules, 2019, 9(10): 551.
2. Siasos G, Paschou SA, Tousoulis D. Mitochondria and diabetes. Ann Transl Med, 2020, 8(6): 262.
3. Ambrosini S, Mohammed SA, Lüscher TF, et al. New mechanisms of vascular dysfunction in cardiometabolic patients: focus on epigenetics. High Blood Press Cardiovasc Prev, 2020, 27(5): 363-371.
4. Siasos G, Skotsimara G, Oikonomou E, et al. Antithrombotic treatment in diabetes mellitus: a review of the literature about antiplatelet and anticoagulation strategies used for diabetic patients in primary and secondary prevention. Curr Pharm Des, 2020, 26(23): 2780-2788.
5. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med, 2008, 358(24): 2545-2559.
6. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med, 2007, 356(24): 2457-2471.
7. Nat Rev Drug Discov. Regulatory watch: FDA issues guidance for cardiovascular risk assessment of novel antidiabetic agents. Nat Rev Drug Discov, 2009, 8(2): 99.
8. Einhorn D. Treatment of glycemic control in diabetes in the CVOT era. J Diabetes, 2020, 12(1): 4.
9. Van der Schueren B, Vrijlandt P, Thomson A, et al. New guideline of the European Medicines Agency (EMA) on the clinical investigation of medicinal products in the treatment and prevention of diabetes mellitus. Diabetologia, 2024, 67(7): 1159-1162.
10. Nathan DM. Finding new treatments for diabetes--how many, how fast. . how good?. N Engl J Med, 2007, 356(5): 437-440.
11. Dicker D. DPP-4 inhibitors: impact on glycemic control and cardiovascular risk factors. Diabetes Care, 2011, 34(Suppl 2): S276-S278.
12. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med, 2013, 369(14): 1317-1326.
13. Heller SR, Bergenstal RM, White WB, et al. Relationship of glycated haemoglobin and reported hypoglycaemia to cardiovascular outcomes in patients with type 2 diabetes and recent acute coronary syndrome events: the EXAMINE trial. Diabetes Obes Metab, 2017, 19(5): 664-671.
14. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2015, 373(3): 232-242.
15. Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk: the CARMELINA randomized clinical trial. JAMA, 2019, 321(1): 69-79.
16. Rosenstock J, Kahn SE, Johansen OE, et al. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes: the CAROLINA randomized clinical trial. JAMA, 2019, 322(12): 1155-1166.
17. Cimmaruta D, Maiorino MI, Scavone C, et al. Efficacy and safety of insulin-GLP-1 receptor agonists combination in type 2 diabetes mellitus: a systematic review. Expert Opin Drug Saf, 2016, 15(2): 77-83.
18. Bunck MC, Cornér A, Eliasson B, et al. Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care, 2011, 34(9): 2041-2047.
19. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2016, 375(4): 311-322.
20. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med, 2016, 375(19): 1834-1844.
21. Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med, 2019, 381(9): 841-851.
22. 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. Lancet, 2018, 392(10157): 1519-1529.
23. Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet, 2019, 394(10193): 121-130.
24. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med, 2015, 373(23): 2247-2257.
25. Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2017, 377(13): 1228-1239.
26. Del Prato S, 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. Lancet, 2021, 398(10313): 1811-1824.
27. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med, 2015, 373(22): 2117-2128.
28. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med, 2017, 377(7): 644-657.
29. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med, 2019, 380(4): 347-357.
30. Bloomgarden Z. The kidney and cardiovascular outcome trials. J Diabetes, 2018, 10(2): 88-89.
31. Jia G, Sowers JR. Hypertension in diabetes: an update of basic mechanisms and clinical disease. Hypertension, 2021, 78(5): 1197-1205.
32. Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia, 2017, 60(2): 215-225.
33. Briasoulis A, Al Dhaybi O, Bakris GL. SGLT2 inhibitors and mechanisms of hypertension. Curr Cardiol Rep, 2018, 20(1): 1.
34. Cruickshank K, Riste L, Anderson SG, et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function?. Circulation, 2002, 106(16): 2085-2090.
35. Viazzi F, Bonino B, Mirijello A, et al. Long-term blood pressure variability and development of chronic kidney disease in type 2 diabetes. J Hypertens, 2019, 37(4): 805-813.
36. Gupta R, Maitz T, Egeler D, et al. SGLT2 inhibitors in hypertension: role beyond diabetes and heart failure. Trends Cardiovasc Med, 2023, 33(8): 479-486.
37. Gupta V, Canovatchel W, Lokesh BN, et al. Sodium-glucose cotransporter-2 inhibitors: moving beyond the glycemic treatment goal. Indian J Endocrinol Metab, 2017, 21(6): 909-918.
38. Wang B, Zhong J, Lin H, et al. Blood pressure-lowering effects of GLP-1 receptor agonists exenatide and liraglutide: a meta-analysis of clinical trials. Diabetes Obes Metab, 2013, 15(8): 737-749.
39. Filippatos T, Tsimihodimos V, Pappa E, et al. Pathophysiology of diabetic dyslipidaemia. Curr Vasc Pharmacol, 2017, 15(6): 566-575.
40. Vergès B. Pathophysiology of diabetic dyslipidaemia: where are we?. Diabetologia, 2015, 58(5): 886-899.
41. Soran H, Schofield JD, Adam S, et al. Diabetic dyslipidaemia. Curr Opin Lipidol, 2016, 27(4): 313-322.
42. Ståhlman M, Pham HT, Adiels M, et al. Clinical dyslipidaemia is associated with changes in the lipid composition and inflammatory properties of apolipoprotein-B-containing lipoproteins from women with type 2 diabetes. Diabetologia, 2012, 55(4): 1156-1166.
43. Yaribeygi H, Maleki M, Reiner Ž, et al. Mechanistic view on the effects of SGLT2 inhibitors on lipid metabolism in diabetic milieu. J Clin Med, 2022, 11(21): 6544.
44. Ejiri K, Miyoshi T, Kihara H, et al. Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure. Sci Rep, 2022, 12(1): 15449.
45. Shi FH, Li H, Shen L, et al. High-dose sodium-glucose co-transporter-2 inhibitors are superior in type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab, 2021, 23(9): 2125-2136.
46. Briand F, Mayoux E, Brousseau E, et al. Empagliflozin, via switching metabolism toward lipid utilization, moderately increases ldl cholesterol levels through reduced ldl catabolism. Diabetes, 2016, 65(7): 2032-2038.
47. Andrikou E, Tsioufis C, Andrikou I, et al. GLP-1 receptor agonists and cardiovascular outcome trials: an update. Hellenic J Cardiol, 2019, 60(6): 347-351.
48. Iorga RA, Bacalbasa N, Carsote M, et al. Metabolic and cardiovascular benefits of GLP-1 agonists, besides the hypoglycemic effect (review). Exp Ther Med, 2020, 20(3): 2396-2400.
49. Stemmer K, Finan B, DiMarchi RD, et al. Insights into incretin-based therapies for treatment of diabetic dyslipidemia. Adv Drug Deliv Rev, 2020, 159: 34-53.
50. Jialal I, Chaudhuri A. Targeting inflammation to reduce ASCVD in type 2 diabetes. J Diabetes Complications, 2019, 33(1): 1-3.
51. Sato T, Aizawa Y, Yuasa S, et al. The effect of dapagliflozin treatment on epicardial adipose tissue volume. Cardiovasc Diabetol, 2018, 17(1): 6.
52. Xu L, Nagata N, Nagashimada M, et al. SGLT2 inhibition by empagliflozin promotes fat utilization and browning and attenuates inflammation and insulin resistance by polarizing M2 macrophages in diet-induced obese mice. EBioMedicine, 2017, 20: 137-149.
53. Salim HM, Fukuda D, Yagi S, et al. Glycemic control with ipragliflozin, a novel selective SGLT2 inhibitor, ameliorated endothelial dysfunction in streptozotocin-induced diabetic mouse. Front Cardiovasc Med, 2016, 3: 43.
54. Dai M, Jia Z, Wang H, et al. Sodium-glucose cotransporter 2 inhibitor ameliorate angiotensin ii-induced hypertension and vascular injury by upregulating FGF21. Inflammation, 2025: 14.
55. Cowie MR, Fisher M. SGLT2 inhibitors: mechanisms of cardiovascular benefit beyond glycaemic control. Nat Rev Cardiol, 2020, 17(12): 761-772.
56. Wu Q, Yao Q, Hu T, et al. Dapagliflozin protects against chronic heart failure in mice by inhibiting macrophage-mediated inflammation, independent of SGLT2. Cell Rep Med, 2023, 4(12): 101334.
57. Wong CK, McLean BA, Baggio LL, et al. Central glucagon-like peptide 1 receptor activation inhibits toll-like receptor agonist-induced inflammation. Cell Metab, 2024, 36(1): 130-143.e5.
58. American Diabetes Association Professional Practice Committee. 10. Cardiovascular disease and risk management: standards of care in diabetes-2025. Diabetes Care, 2025, 48(Suppl 1): S207-S238.
59. Marx N, Federici M, Schütt K, et al. 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J, 2023, 44(39): 4043-4140.
60. 中华医学会糖尿病学分会. 中国糖尿病防治指南(2024 版). 中华糖尿病杂志, 2025, 17(1): 16-139.

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