Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease (DELIGHT): a randomised, double-blind, placebo-controlled trial

Coutinho, 1999, The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95 783 individuals followed for 12·4 years, Diabetes Care, 22, 233, 10.2337/diacare.22.2.233 Fox, 2013, Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis, Lancet, 380, 1662, 10.1016/S0140-6736(12)61350-6 Perkovic, 2013, Intensive glucose control improves kidney outcomes in patients with type 2 diabetes, Kidney Int, 83, 517, 10.1038/ki.2012.401 Zoungas, 2017, Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials, Lancet Diabetes Endocrinol, 5, 431, 10.1016/S2213-8587(17)30104-3 Heerspink, 2019, Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials, Lancet Diabetes Endocrinol, 7, 128, 10.1016/S2213-8587(18)30314-0 Heerspink, 2016, Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes: cardiovascular and kidney effects, potential mechanisms and clinical applications, Circulation, 134, 752, 10.1161/CIRCULATIONAHA.116.021887 Muskiet, 2017, GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes, Nat Rev Nephrol, 13, 605, 10.1038/nrneph.2017.123 Petrykiv, 2017, Differential effects of dapagliflozin on cardiovascular risk factors at varying degrees of renal function, Clin J Am Soc Nephrol, 12, 751, 10.2215/CJN.10180916 Dekkers, 2018, Effects of the sodium-glucose co-transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes and stages 3b–4 chronic kidney disease, Nephrol Dial Transplant, 33, 2005, 10.1093/ndt/gfx350 Perkovic, 2018, Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials, Lancet Diabetes Endocrinol, 6, 691, 10.1016/S2213-8587(18)30141-4 Fioretto, 2016, Dapagliflozin reduces albuminuria over 2 years in patients with type 2 diabetes mellitus and renal impairment, Diabetologia, 59, 2036, 10.1007/s00125-016-4017-1 Cherney, 2017, Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial, Lancet Diabetes Endocrinol, 5, 610, 10.1016/S2213-8587(17)30182-1 Wiviott, 2019, Dapagliflozin and cardiovascular outcomes in type 2 diabetes, N Engl J Med, 380, 347, 10.1056/NEJMoa1812389 Heerspink, 2017, Canagliflozin slows progression of renal function decline independently of glycemic effects, J Am Soc Nephrol, 28, 368, 10.1681/ASN.2016030278 Heerspink, 2016, Dapagliflozin reduces albuminuria in patients with diabetes and hypertension receiving renin-angiotensin blockers, Diabetes Obes Metab, 18, 590, 10.1111/dom.12654 Mosenzon, 2017, Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial, Diabetes Care, 40, 69, 10.2337/dc16-0621 Rosenstock, 2019, 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, 321, 69, 10.1001/jama.2018.18269 Groop, 2017, Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: the randomized MARLINA-T2D trial, Diabetes Obes Metab, 19, 1610, 10.1111/dom.13041 Levey, 2007, Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values, Clin Chem, 53, 766, 10.1373/clinchem.2006.077180 Matsuo, 2009, Revised equations for estimated GFR from serum creatinine in Japan, Am J Kidney Dis, 53, 982, 10.1053/j.ajkd.2008.12.034 Chen, 2014, Modification of diet in renal disease (MDRD) study and CKD epidemiology collaboration (CKD-EPI) equations for Taiwanese adults, PLoS One, 9, e99645, 10.1371/journal.pone.0099645 Men, 2018, Efficacy and safety of saxagliptin in patients with type 2 diabetes: a systematic review and meta-analysis, PLoS One, 13, e0197321, 10.1371/journal.pone.0197321 Ptaszynska, 2014, Safety profile of dapagliflozin for type 2 diabetes: pooled analysis of clinical studies for overall safety and rare events, Drug Saf, 37, 815, 10.1007/s40264-014-0213-4 Rosenstock, 2015, Dual add-on therapy in type 2 diabetes poorly controlled with metformin monotherapy: a randomized double-blind trial of saxagliptin plus dapagliflozin addition versus single addition of saxagliptin or dapagliflozin to metformin, Diabetes Care, 38, 376, 10.2337/dc14-1142 Mathieu, 2015, Randomized, double-blind, phase 3 trial of triple therapy with dapagliflozin add-on to saxagliptin plus metformin in type 2 diabetes, Diabetes Care, 38, 2009, 10.2337/dc15-0779 Heerspink, 2016, Is a reduction in albuminuria associated with renal and cardiovascular protection? A post hoc analysis of the ALTITUDE trial, Diabetes Obes Metab, 18, 169, 10.1111/dom.12600 de Zeeuw, 2004, Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL, Kidney Int, 65, 2309, 10.1111/j.1523-1755.2004.00653.x Panchapakesan, 2013, Effects of SGLT2 inhibition in human kidney proximal tubular cells—renoprotection in diabetic nephropathy?, PLoS One, 8, e54442, 10.1371/journal.pone.0054442 Esterline, 2018, Mechanisms in endocrinology: SGLT2 inhibitors: clinical benefits by restoration of normal diurnal metabolism?, Eur J Endocrinol, 178, R113, 10.1530/EJE-17-0832 Gilbert, 2016, SGLT2 inhibitors: β blockers for the kidney?, Lancet Diabetes Endocrinol, 4, 814, 10.1016/S2213-8587(16)30237-6 Kohan, 2014, Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control, Kidney Int, 85, 962, 10.1038/ki.2013.356 Fioretto, 2018, Efficacy and safety of dapagliflozin in patients with type 2 diabetes and moderate renal impairment (chronic kidney disease stage 3A): the DERIVE study, Diabetes Obes Metab, 20, 2532, 10.1111/dom.13413 Neal, 2017, Canagliflozin and cardiovascular and renal events in type 2 diabetes, N Engl J Med, 377, 644, 10.1056/NEJMoa1611925 Jabbour, 2018, Dapagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of safety data from phase IIb/III clinical trials, Diabetes Obes Metab, 20, 620, 10.1111/dom.13124