Petrie J, Guzik T, Touyz R. Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms. Can J Cardiol. 2018;34(5):575–84.

Article  PubMed  Google Scholar 

Baker W, Smyth L, Riche D, Bourret E, Chamberlin K, White W. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: a systematic review and meta-analysis. J Am Soc Hypertens. 2014;8(4):262–75.

Article  CAS  PubMed  Google Scholar 

Mazidi M, Rezaie P, Gao HK, Kengne AP. Effect of sodium-glucose cotransport-2 inhibitors on blood pressure in people with type 2 diabetes mellitus: a systematic review and meta-analysis of 43 randomized control trials with 22 528 patients. J Am Heart Assoc. 2017;6(6):e004007.

Georgianos P, Agarwal R. Ambulatory blood pressure reduction with SGLT-2 inhibitors: dose-response meta-analysis and comparative evaluation with low-dose hydrochlorothiazide. Diabetes Care. 2019;42(4):693–700.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Amin NB, Wang X, Mitchell JR, Lee DS, Nucci G, Rusnak JM. Blood pressure-lowering effect of the sodium glucose co-transporter-2 inhibitor ertugliflozin, assessed via ambulatory blood pressure monitoring in patients with type 2 diabetes and hypertension. Diabetes Obes Metab. 2015;17(8):805–8.

Article  CAS  PubMed  Google Scholar 

Cherney D, Cooper M, Tikkanen I, Pfarr E, Johansen OE, Woerle H, et al. Pooled analysis of phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin. Kidney Int. 2018;93(1):231–44.

Article  CAS  PubMed  Google Scholar 

• Ye N, Jardine M, Oshima M, Hockham C, Heerspink H, Agarwal R, et al. Blood pressure effects of canagliflozin and clinical outcomes in type 2 diabetes and chronic kidney disease. Circulation. 2021;143:1735–49. The findings from this study demonstrated that the blood pressure lowering effects of SGLT2 inhibitors are similarly applicable to patients with chronic kidney disease and resistant hypertension, expanding on previous trials which excluded these populations. This broadened the cohort who were considered to benefit from these agents.

Baker W, Buckley L, Kelly M, Bucheit J, Parod E, Brown R, et al. Effects of sodium-glucose cotransporter 2 inhibitors on 24-hour ambulatory blood pressure: a systematic review and meta-analysis. J Am Heart Assoc. 2017;6(5):e005686.

Townsend R, Machin I, Ren J, Trujillo A, Kawaguchi M, Vijapurkar U, et al. Reductions in mean 24-hour ambulatory blood pressure after 6-week treatment with canagliflozin in patients with type 2 diabetes Mellitus and hypertension. J Clin Hypertens (Greenwich). 2016;18(1):43–52.

Article  CAS  PubMed  Google Scholar 

Kario K, Okada K, Kato M, Nishizawa M, Yoshida T, Asano T, et al. Twenty-four-hour blood pressure–lowering effect of a sodium-glucose cotransporter 2 inhibitor in patients with diabetes and uncontrolled nocturnal hypertension. Circulation. 2018;139:2089–97.

Article  PubMed  PubMed Central  Google Scholar 

Takeshige Y, Fujisawa Y, Rahman A, Kittikuluth W, Nakano D, Mori H, et al. A sodium-glucose co-transporter 2 inhibitor empagliflozin prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats. Hypertens Res. 2016;39(6):415–22.

Article  CAS  PubMed  Google Scholar 

Heerspink H, Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013;15(9):853–62.

Article  PubMed Central  Google Scholar 

Tikkanen I, Narko K, Zeller C, Green A, Salsali A, Broedl U, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015;38(3):420–8.

Article  CAS  PubMed  Google Scholar 

Posch M, Walther N, Ferrannini E, Powell D, Banks P, Wason S, et al. Metabolic, intestinal, and cardiovascular effects of sotagliflozin compared with empagliflozin in patients with type 2 diabetes: a randomized, double-blind study. Diabetes Care. 2022;45(9):2118–26.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neuen B, Young T, Heerspik H, Neal B, Perkovic V, Billot L. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(11):845–54.

Article  CAS  PubMed  Google Scholar 

Perkovic V, Jardine M, Neal B, Bompoint S, Heerspink H, Charytan D, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380:2295–306.

Article  CAS  PubMed  Google Scholar 

Sen T, Scholtes R, Greasley P, Cherney D, Dekkers C, Vervloet M, et al. Effects of dapagliflozin on volume status and systemic haemodynamics in patients with chronic kidney disease without diabetes: results from DAPASALT and DIAMOND. Diabetes Obes Metab. 2022;24(8):1578–87.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Wheeler D, Toto R, Stefansson B, Jongs N, Chertow G, Greene T, et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. 2021;100(1):215–44. The subgroup analysis of DAPA-CKD presented in this study demonstrated the renoprotective effects of SGLT2 inhibitors in patients with chronic kidney disease secondary to IgA nephropathy. These findings demonstrated the utility of these agents in a non-diabetic chronic kidney disease population.

Wheeler D, Jongs N, Stefansson B, Chertow G, Greene T, Hou FF, et al. Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial. Nephrol Dial Transplant. 2022;37(9):1647–56.

Article  CAS  PubMed  Google Scholar 

Ferreira J, Fitchett D, Ofstad AP, Kraus B, Wanner C, Zwiener I, et al. Empagliflozin for patients with presumed resistant hypertension: a post hoc analysis of the EMPA-REG OUTCOME trial. Am J Hypertens. 2020;33(12):1092–101.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Provenzano M, Puchades MJ, Garofalo C, Jongs N, D’Marco L, Andreucci M, et al. Albuminuria-lowering effect of dapagliflozin, eplerenone, and their combination in patients with chronic kidney disease: a randomized crossover clinical trial. J Am Soc Nephrol. 2022;33(8):1569–80.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neuen B, Oshima M, Agarwal R, Arnott C, Cherney D, Edwards R, et al. Sodium-glucose cotransporter 2 inhibitors and risk of hyperkalemia in people with type 2 diabetes: a meta-analysis of individual participant data From randomized, controlled trials. Circulation. 2022;145:1460–70.

Article  CAS  PubMed  Google Scholar 

Vaduganathan M, Docherty KF, Claggett BL, Jhund PS, de Boer RA, Hernandez AF, et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet. 2022;400(10354):757–67.

Article  CAS  PubMed  Google Scholar 

Martinez F, Serenelli M, Nicolau J, Petrie M, Chiang CE, Tereshchenko S, et al. Efficacy and safety of dapagliflozin in heart failure with reduced ejection fraction according to age. Circulation. 2020;141:100–11.

Article  CAS  PubMed  Google Scholar 

Serenelli M, Bohm M, Inzucchi S, Kober L, Kosiborod M, Martinez F, et al. Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and prevention of adverse outcomes in heart failure trial (DAPA-HF). Eur Heart J. 2020;41(36):3402–18.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Anker S, Butler J, Filippatos G, Ferreira J, Bocchi E, Bohm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451–61.

Article  CAS  PubMed  Google Scholar 

Packer M. Lack of durable natriuresis and objective decongestion following SGLT2 inhibition in randomized controlled trials of patients with heart failure. Cardiovasc Diabetol. 2023;22(1):197.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wilcox CS. Antihypertensive and renal mechanisms of SGLT2 (sodium-glucose linked transporter 2) inhibitors. Hypertension. 2020;75(4):894–901.

Article  CAS  PubMed  Google Scholar 

Onishi A, Fu Y, Patel R, Darshi M, Crespo-Masip M, Huang W, et al. A role for tubular Na+/H+ exchanger NHE3 in the natriuretic effect of the SGLT2 inhibitor empagliflozin. Am J Physiol Renal Physiol. 2020;319(4):F712–28.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Huang W, Patel R, Onishi A, Masip MC, Soleimani M, Freeman B, et al. Tubular NHE3 is a determinant of the acute natriuretic and chronic blood pressure lowering effect of the SGLT2 inhibitor empagliflozin. FASEB J. 2018;32(S1):620–17.

Mayne K. Effects of empagliflozin on fluid overload in chronic kidney disease: an EMPA-KIDNEY bioimpedance substudy University of Oxford, Oxford, United Kingdom: Clinical Trial Service Unit and Epidemiological Studies Unit 2023. Available from: https://www.empakidney.org/downloads.

Cherney D, Perkins B, Soleymanlou N, Maione M, Lai V, Lee L, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129:587–97.

Chilton R, Tikkanen I, Cannon CP, Crowe S, Woerle H, Boedl UC, et al. Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes. Diabetes Obes Metab. 2015;17(12):1180–93.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lambers Heerspink H, De Zeeuw D, Wie L, Leslie B, List J. Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab. 2013;15(9):853–62.

Article  CAS  PubMed  Google Scholar 

Hallow KM, Helmlinger G, Greasley PJ, McMurray JJ, Boulton DW. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obes Metab. 2018;20(3):479–87.

Article  CAS  PubMed  Google Scholar 

Mazer CD, Hare GM, Connelly PW, Gilbert RE, Shehata N, Quan A, et al. Effect of empagliflozin on erythropoietin levels, iron stores, and red blood cell morphology in patients with type 2 diabetes mellitus and coronary artery disease. Circulation. 2020;141(8):704–7.

Article  PubMed  Google Scholar 

Oshima M, Neuen BL, Jardine MJ, Bakris G, Edwards R, Levin A, et al. Effects of canagliflozin on anaemia in patients with type 2 diabetes and chronic kidney disease: a post-hoc analysis from the CREDENCE trial. Lancet Diabetes Endocrinol. 2020;8(11):903–14.

Article  CAS  PubMed  Google Scholar 

Docherty KF, Curtain JP, Anand IS, Bengtsson O, Inzucchi SE, Køber L, et al. Effect of dapagliflozin on anaemia in DAPA-HF. Eur J Heart Fail. 2021;23(4):617–28.

Article  CAS  PubMed  Google Scholar