Hidalgo Santiago JC, et al. Effect of dapagliflozin on arterial stiffness in patients with type 2 diabetes mellitus. Med Clin (Barc). 2020;154(5):171–4.

Article  CAS  PubMed  Google Scholar 

Zinman B, et al. Empagliflozin, Cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28.

Article  CAS  PubMed  Google Scholar 

Neal B, et al. Canagliflozin and Cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57.

Article  CAS  PubMed  Google Scholar 

McDonagh TA et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J, 2023. 44(37): pp. 3627–3639.

KDIGO 2024 Clinical Practice Guideline for the evaluation and management of chronic kidney disease. Kidney Int, 2024. 105(4s): pp. S117–314.

Ferrannini E, Mark M, Mayoux E. CV Protection in the EMPA-REG OUTCOME Trial: a thrifty substrate hypothesis. Diabetes Care. 2016;39(7):1108–14.

Article  PubMed  Google Scholar 

Perrone-Filardi P, et al. Mechanisms linking empagliflozin to cardiovascular and renal protection. Int J Cardiol. 2017;241:450–6.

Article  PubMed  Google Scholar 

Sas KM, et al. Metabolomics and diabetes: analytical and computational approaches. Diabetes. 2015;64(3):718–32.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Klein MS, Shearer J. Metabolomics and type 2 diabetes: translating Basic Research into Clinical Application. J Diabetes Res. 2016;2016:p3898502.

Article  Google Scholar 

Kappel BA, et al. Effect of Empagliflozin on the metabolic signature of patients with type 2 diabetes Mellitus and Cardiovascular Disease. Circulation. 2017;136(10):969–72.

Article  CAS  PubMed  Google Scholar 

Mulder S, et al. Effects of dapagliflozin on urinary metabolites in people with type 2 diabetes. Diabetes Obes Metab. 2019;21(11):2422–8.

Article  CAS  PubMed  Google Scholar 

Bletsa E, et al. Effect of Dapagliflozin on urine metabolome in patients with type 2 diabetes. J Clin Endocrinol Metab. 2021;106(5):1269–83.

Article  PubMed  PubMed Central  Google Scholar 

Shao M, et al. Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns. Diabetologia. 2024;67(4):738–54.

Article  CAS  PubMed  Google Scholar 

Eriksson L, Wold TJ. CV-ANOVA for significance testing of PLS and OPLS (R) models. J Chemom. 2008;22:594–600.

Article  CAS  Google Scholar 

Monami M, Nardini C, Mannucci E. Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2014;16(5):457–66.

Article  CAS  PubMed  Google Scholar 

Tsimihodimos V, Filippatos TD, Elisaf MS. SGLT2 inhibitors and the kidney: effects and mechanisms. Diabetes Metab Syndr. 2018;12(6):1117–23.

Article  CAS  PubMed  Google Scholar 

Salah HM et al. Sodium-glucose cotransporter 2 inhibitors and Cardiac Remodeling. J Cardiovasc Transl Res, 2022.

Filippas-Ntekouan S, et al. SGLT-2 inhibitors: pharmacokinetics characteristics and effects on lipids. Expert Opin Drug Metab Toxicol. 2018;14(11):1113–21.

CAS  PubMed  Google Scholar 

Chino Y, et al. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. Biopharm Drug Dispos. 2014;35(7):391–404.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Taylor SI, Blau JE, Rother KI. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015;3(1):8–10.

Article  CAS  PubMed  Google Scholar 

Maejima Y. SGLT2 inhibitors play a salutary role in heart failure via modulation of the mitochondrial function. Front Cardiovasc Med. 2019;6:186.

Article  CAS  PubMed  Google Scholar 

Bonner C, et al. Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med. 2015;21(5):512–7.

Article  CAS  PubMed  Google Scholar 

Zhang X, et al. Dapagliflozin attenuates heart failure with preserved ejection fraction remodeling and dysfunction by elevating β-Hydroxybutyrate-activated citrate synthase. J Cardiovasc Pharmacol. 2023;82(5):375–88.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chase D, et al. Empagliflozin improves cardiac energetics during ischaemia/reperfusion by directly increasing cardiac ketone utilization. Cardiovasc Res. 2023;119(16):2672–80.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pherwani S, et al. Ketones provide an extra source of fuel for the failing heart without impairing glucose oxidation. Metabolism. 2024;154:155818.

Article  CAS  PubMed  Google Scholar 

Kolb H, et al. Ketone bodies: from enemy to friend and guardian angel. BMC Med. 2021;19(1):313.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang DD, et al. Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure. Cardiovasc Diabetol. 2024;23(1):197.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim SR, et al. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun. 2020;11(1):2127.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gopalasingam N et al. Randomized crossover trial of 2-Week Ketone Ester Treatment in patients with type 2 diabetes and heart failure with preserved ejection fraction. Circulation, 2024.

Liu JJ, et al. Urine tricarboxylic acid cycle metabolites Predict Progressive chronic kidney disease in type 2 diabetes. J Clin Endocrinol Metab. 2018;103(12):4357–64.

Article  PubMed  Google Scholar 

Forbes JM, Thorburn DR. Mitochondrial dysfunction in diabetic kidney disease. Nat Rev Nephrol. 2018;14(5):291–312.

Article  CAS  PubMed  Google Scholar 

Bourgonje AR et al. Plasma citrate levels are Associated with an increased risk of Cardiovascular Mortality in patients with type 2 diabetes (Zodiac-64). J Clin Med, 2023. 12(20).

Menni C, et al. Biomarkers for type 2 diabetes and impaired fasting glucose using a nontargeted metabolomics approach. Diabetes. 2013;62(12):4270–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Floegel A, et al. Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes. 2013;62(2):639–48.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang TJ, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17(4):448–53.

Article  PubMed  PubMed Central  Google Scholar 

Teunis C, Nieuwdorp M, Hanssen N. Interactions between Tryptophan Metabolism, the gut microbiome and the Immune System as potential drivers of non-alcoholic fatty liver Disease (NAFLD) and metabolic diseases. Metabolites, 2022. 12(6).

King NJ, Thomas SR. Molecules in focus: indoleamine 2,3-dioxygenase. Int J Biochem Cell Biol. 2007;39(12):2167–72.

Article  CAS  PubMed  Google Scholar