Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE)

Abstract

Background Despite available interventions, people with type 2 diabetes (T2D) remain at risk of chronic kidney disease (CKD). Finerenone, a potent and selective nonsteroidal mineralocorticoid receptor antagonist, and sodium–glucose co-transporter 2 inhibitors (SGLT2is) can reduce both kidney and cardiovascular risks in people with CKD and T2D. Here we outline the design of a study to investigate whether dual therapy with finerenone and a SGLT2i is superior to either agent alone. Methods CONFIDENCE (NCT05254002) is a randomized, controlled, double-blind, double-dummy, international, multicentre, three-armed, parallel-group, 7.5–8.5-month, Phase 2 study in approximately 807 adults with T2D, stage 2–3 CKD and a urine albumin-to-creatinine ratio (UACR) from ≥ 300–<5000 mg/g. The primary objective is to demonstrate that 6 months’ dual therapy comprising finerenone and the SGLT2i empagliflozin is superior for reducing albuminuria versus either agent alone. Interventions will be once-daily finerenone 10 mg or 20 mg (target dose) plus empagliflozin 10 mg, or empagliflozin 10 mg alone, or finerenone 10 mg or 20 mg (target dose) alone. Results The primary outcome is relative change from baseline in UACR among the three groups. Secondary outcomes will further characterize efficacy and safety, including change in eGFR and incident hyperkalaemia. Conclusions CONFIDENCE is evaluating the safety, tolerability and efficacy of dual use of finerenone and a SGLT2i in adults with CKD and T2D. Should an additive effect be shown, early and efficient intervention with dual finerenone and SGLT2i therapy could slow disease progression and provide long-term benefits for people with CKD and T2D.

Combination therapy with an SGLT‐2 inhibitor and finerenone in DKD: Are we there yet?

“…11,14 We need to await the completion of the ongoing CONFIDENCE trial to derive a more conclusive answer to this crucial research question. 15 If this trial demonstrates that the combination of empagliflozin plus finerenone offers an additive albuminuria-lowering effect as compared with either monotherapy, then there will be a strong scientific basis to implement this combination in daily clinical practice with the aim to provide the greatest cardiorenal protection to high-risk patients with overt DKD.…”

“…These patients will be randomized in a 1:1:1 ratio to receive double-blind therapy with finerenone (10-20 mg/day) and matching placebo, empagliflozin (10 mg/day) and matching placebo, or the combination of finerenone (10-20 mg/day) plus empagliflozin (10 mg/day) over a follow-up period of 6 months. 15 The primary outcome of this trial is defined as the between-group difference in the change from baseline in UACR. Secondary outcomes, such as between-group differences in changes of eGFR and incidence of hyperkalemia, will further elucidate the tolerability and safety of combination therapy.…”

“…Secondary outcomes, such as between-group differences in changes of eGFR and incidence of hyperkalemia, will further elucidate the tolerability and safety of combination therapy. 15…”

Comparison the effects of finerenone and SGLT2i on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus: A network meta-analysis

“…Head-to-head studies using finerenone and SGLT2i in patients with CKD or CVD are currently underway. The CONFIDENCE study may provide additional data on whether the combination of finerenone and SGLT2i produces stronger cardiovascular and renal protective effects compared to these drugs alone ( 23 ). Sotagliflozin has dual inhibitory effects on SGLT1 and SGLT2.…”

Finerenone in SGLT-2 Inhibitors Era: Current Positioning in Diabetic Kidney Disease

“…No episode of hyperkalemia was noted with dapagliflozin (0%) [29]. An ongoing 6-month (n = 807), double-blind, three-arm study (CONFIDENCE, NCT052-54002) that is currently assessing the efficacy (change in UACR as the primary outcome and changes in eGFR as secondary outcome) and safety (incidence of hyperkalemia) of finerenone (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) [12]) ACEi -angiotensin-converting enzyme inhibitors, ARBs -angiotensin II receptor blockers; CI -confidence interval; CKDchronic kidney disease; CV -cardiovascular; HR -hazard ratio; MRA -mineralocorticoid receptor antagonists; RR -risk ratio; SGLT2i -sodium-glucose cotransporter-2 inhibitors 300-5000 mg/g) and T2DM will further enlighten the relative merits of these agents in near future [30].…”