Finerenone with empagliflozin according to body mass index in chronic kidney disease and type 2 diabetes

Background Obesity is associated with the onset and progression of both type 2 diabetes (T2D) and chronic kidney disease (CKD). However, whether obesity status modifies the benefits of empagliflozin, finerenone, or both on cardiovascular-kidney-metabolic (CKM) risk factors remains uncertain. Purpose To 1) ascertain the effect of empagliflozin, finerenone, and the combination of empagliflozin and finerenone on body weight in persons with CKD and T2D; and 2) examine whether body mass index (BMI) modifies the effects of these therapies on CKM health parameters. Methods This exploratory analysis of the CONFIDENCE trial included participants with available BMI at baseline. First, we examined the effect of empagliflozin, finerenone, and combination therapy on body weight change between baseline and 210 days. Second, we evaluated changes in urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), systolic blood pressure, and glycated hemoglobin (HbA1c) levels according to treatment and baseline BMI. Results Among 800 trial participants, higher baseline BMI was associated with a worse cardiometabolic profile, higher eGFR, and lower serum potassium levels. Participants in all treatment arms experienced reductions in body weight over the treatment period (baseline to 180 days), which were greater among those randomized to empagliflozin (average treatment effect, -1.0 kg; 95% CI, -1.2 to -0.7; P<0.001) and the combination of empagliflozin and finerenone (average treatment effect, -1.0 kg; 95% CI, -1.3 to -0.8; P<0.001) compared with finerenone alone (average treatment effect, -0.5 kg; 95% CI, -0.8 to -0.2; P<0.001) (Figure 1). Changes appeared at least partially reversible after protocolized withdrawal. Compared with finerenone, treatment with empagliflozin (odds ratio [OR], 1.88; 95% CI, 1.18-2.99) or combination therapy (OR, 1.68; 95% CI, 1.05-2.69) was associated with higher odds of ≥5% body weight reduction by day 180. Among those randomized to empagliflozin or combination therapy, the magnitude of body weight reduction was greater among participants with higher baseline BMI (Figure 1). Baseline BMI did not appear to modify the effect of each of the therapies on UACR (Pinteraction=0.99), eGFR (Pinteraction=0.98), or HbA1c (Pinteraction=0.29). However, greater reductions in systolic blood pressure were observed with empagliflozin and combination therapy versus finerenone alone at higher baseline BMI (Pinteraction=0.049) (Figure 2). Conclusions These findings support combination therapy with empagliflozin and finerenone to maximize reductions in albuminuria among persons with CKD and T2D, irrespective of BMI. Reductions in body weight with this approach may represent an important ancillary benefit in this population.