Bayer Ag · XETR:BAYN
Bayer — World Congress of Nephrology 2026
56 slides from Bayer's conference presentation, March 2026
Slide 1: World Congress of Nephrology 2026, Yokohama
PSN weit 6 MARCH 28-31, 2026 | YOKOHAMA, JAPAN
Slide 2: Effect of Simultaneous Initiation of Finerenone and Empagliflozin on UACR by Age and Sex
EFFECT OF SIMULTANEOUS INITIATION OF FINERENONE AND EMPAGLIFLOZIN ON URINARY ALBUMIN-TO-CREATININE RATIO BY AGE AND SEX IN THE RANDOMIZED CONFIDENCE TRIAL WCN26-AB-7771 Rajiv Agarwal, MD, MS Consultant Nephrologist Richard L Roudebush VA Medical Center and Indiana University School of Medicine India
Slide 3: Disclosures
DISCLOSURES Nonfinancial support from Akebia Therapeutics, Alnylam, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Intercept, and Novartis Consulting fees from Akebia Therapeutics, Alnylam, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Intercept, and Novartis Royalties or li
Slide 4: Females and CV Risk in T2D
FEMALES AND CV RISK IN T2D Paradoxical loss of CV protection in females with diabetes 1.86 2.42 CV Mortality†,2 CV Mortality†,2 Females with diabetes have a 2-fold excess CV risk compared with males with diabetes1 Females with diabetes have an earlier onset of fatal MI than males with diabetes1 †Rel
Slide 5: The Age Paradox
THE AGE PARADOX Earlier onset of T2D significantly increases relative risk for complications,1 yet older patients face the most prescribing hesitancy2,3 In people with diabetes, CKD magnifies CV risk significantly4,5 CKD, chronic kidney disease; CV, cardiovascular; T2D, type 2 diabetes. 1. Morton JI
Slide 6: Critical Gaps in Precision Nephrology
CRITICAL GAPS IN PRECISION NEPHROLOGY SGLT2i trials lack Longitudinal age-response Treatment benefit disparity sex-stratified relationship remains by age and sex is essentially albuminuria data undefined unknown Study Baseline eGFR subgroups Sex-specific UACR outcomes EMPA-REG OUTCOME1 ◯ CANVAS Prog
Slide 7: Resolving the Knowledge Gap
RESOLVING THE KNOWLEDGE GAP Primary aim Evaluate baseline clinical characteristics and longitudinal changes in UACR across specific age and sex cohorts UACR, urinary albumin-to-creatinine ratio. 7
Slide 8: Resolving the Knowledge Gap
RESOLVING THE KNOWLEDGE GAP Primary aim Secondary aim Quantify the independent Evaluate baseline clinical effects of age and sex on the characteristics and anti-albuminuric efficacy of longitudinal changes in finerenone, UACR across specific age empagliflozin, or their and sex cohorts simultaneous c
Slide 9: Resolving the Knowledge Gap
RESOLVING THE KNOWLEDGE GAP Primary aim Secondary aim Safety objective Quantify the independent Evaluate baseline clinical effects of age and sex on the Determine if safety profiles characteristics and anti-albuminuric efficacy of (specifically AKI and longitudinal changes in finerenone, hyperkalemi
Slide 10: CONFIDENCE Trial Design
CONFIDENCE TRIAL DESIGN Participants were randomized in a 1:1:1 ratio to one of three parallel groups Start of Treatment End of End treatment period treatment of trial Stratification: Finerenone (10 mg or 20 mg once daily) UACR, mg/g and empagliflozin (10 mg once daily) (≤850, >850) R Primary effica
Slide 11: Statistical Methodology: Linear Mixed-Effects Modeling
STATISTICAL METHODOLOGY: LINEAR MIXED-EFFECTS MODELING† Fixed effects Linear mixed-effects model Treatment Visit Treatment-by-visit interaction Estimated mean Region change in UACR eGFR stratum UACR stratum Age Maximal likelihood estimation: Random effects: Subject and visit Sex †A linear mixed mode
Slide 12: Resolving the Knowledge Gap
RESOLVING THE KNOWLEDGE GAP Primary aim Secondary aim Safety objective Quantify the independent Evaluate baseline clinical effects of age and sex on the Determine if safety profiles characteristics and anti-albuminuric efficacy of (specifically AKI and longitudinal changes in finerenone, hyperkalemi
Slide 13: UACR Reduction Scales with Age and Sex
UACR REDUCTION SCALES WITH AGE AND SEX† Females Finerenone + empagliflozin Finerenone Empagliflozin Age (years) 20 48 0 –20 –40 –60 Age (years) –80 48 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 Days since treatment initiation Days since treatment initiation Days since treatment initiat
Slide 14: UACR Reduction Scales with Age and Sex
UACR REDUCTION SCALES WITH AGE AND SEX† Females Finerenone + empagliflozin Finerenone Empagliflozin Age (years) 20 48 0 60 –20 –40 –60 Age (years) –80 48 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 60 Days since treatment initiation Days since treatment initiation Days since treatment i
Slide 15: UACR Reduction Scales with Age and Sex
UACR REDUCTION SCALES WITH AGE AND SEX† Females Finerenone + empagliflozin Finerenone Empagliflozin Age (years) 20 48 0 60 –20 68 –40 –60 Age (years) –80 48 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 60 Days since treatment initiation Days since treatment initiation Days since treatmen
Slide 16: UACR Reduction Scales with Age and Sex
UACR REDUCTION SCALES WITH AGE AND SEX† Females Finerenone + empagliflozin Finerenone Empagliflozin Age (years) 20 48 0 60 –20 68 74 –40 –60 Age (years) –80 48 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 60 Days since treatment initiation Days since treatment initiation Days since treat
Slide 17: UACR Reduction Scales with Age and Sex
UACR REDUCTION SCALES WITH AGE AND SEX† Females Finerenone + empagliflozin Finerenone Empagliflozin Age (years) 20 48 Change in UACR from 0 60 baseline (%) –20 68 74 –40 80 –60 Age (years) –80 48 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 60 Days since treatment initiation Days since t
Slide 18: Resolving the Knowledge Gap
RESOLVING THE KNOWLEDGE GAP Primary aim Secondary aim Safety objective Quantify the independent Evaluate baseline clinical effects of age and sex on the Determine if safety profiles characteristics and anti-albuminuric efficacy of (specifically AKI and longitudinal changes in finerenone, hyperkalemi
Slide 19: Distribution by Biological Sex
DISTRIBUTION BY BIOLOGICAL SEX Female 25% (n=198) Male 75% (n=600) 13
Slide 20: Baseline Characteristics by Biological Sex
BASELINE CHARACTERISTICS BY BIOLOGICAL SEX Female (n=198) Male (n=600) Median UACR 548 mg/g UACR 592 mg/g ASCVD prevalence 23% ASCVD 30% Mean BMI 29.8 kg/m2 BMI 29.1 kg/m2 Mean eGFR 54 mL/min/1.73 m2 eGFR 54 mL/min/1.73 m2 ASCVD, atherosclerotic cardiovascular disease; BMI, body mass index; CV, card
Slide 21: Baseline Characteristics by Biological Sex
BASELINE CHARACTERISTICS BY BIOLOGICAL SEX Female (n=198) Male (n=600) Median UACR 548 mg/g UACR 592 mg/g ASCVD prevalence 23% ASCVD 30% Mean BMI 29.8 kg/m2 BMI 29.1 kg/m2 Mean eGFR 54 mL/min/1.73 m2 eGFR 54 mL/min/1.73 m2 Females entered the trial with numerically lower baseline albuminuria and CV
Slide 22: Significant Sexual Dimorphism in Treatment Response Amplifies Over Time
SIGNIFICANT SEXUAL DIMORPHISM IN TREATMENT RESPONSE AMPLIFIES OVER TIME Males (reference) Treatment difference in –5 UACR reduction (%) Females –6.9% –10 Males –9.5% –15 –18.6% –20 UACR, urinary albumin-to-creatinine ratio. 15
Slide 23: Sexual Dimorphism Persists After Treatment Discontinuation
SIGNIFICANT SEXUAL DIMORPHISM IN TREATMENT RESPONSE PERSISTS AFTER TREATMENT DISCONTINUATION 18.6% 16.6% Greater reduction in UACR for Sustained greater reduction females than males at Day at Day 210, 30 days 180 (p=0.008) post-treatment Day 180 Day 210 UACR, urinary albumin-to-creatinine ratio. 16
Slide 24: Sexual Dimorphism in Response Is Independent of Treatment
SIGNIFICANT SEXUAL DIMORPHISM IN TREATMENT RESPONSE IS INDEPENDENT OF TREATMENT Sex interaction p=0.46 17
Slide 25: Older Age: Lower eGFR and More ASCVD
OLDER AGE LOWER eGFR AND MORE ASCVD Q1 Q2 Q3 Q4 ≤60 years 61–68 years 69–74 years >74 years eGFR (mL/min/1.73 m2), 57 56 52 51 mean Decrease 14 27 37 36 ASCVD, % Increase Statin use, % 66 74 83 78 Predominantly Geography Predominantly Asia (53%) North America/Europe (64%) ASCVD, atherosclerotic ca
Slide 26: UACR Reduction Scales Linearly with Age
UACR REDUCTION SCALES LINEARLY WITH AGE Change in UACR from baseline per 0 10-year age increase (%) –10.2% −5 −10 −15 0 14 30 90 180 210 Days since treatment initiation UACR, urinary albumin-to-creatinine ratio. 19
Slide 27: Quantifying the 10-Year Incremental Benefit
QUANTIFYING THE 10-YEAR INCREMENTAL BENEFIT† Day 14 −4.5% †UACR reductions per 10-year increase in age, calculated at each study timepoint. UACR, urinary albumin-to-creatinine ratio. 20
Slide 28: Quantifying the 10-Year Incremental Benefit
QUANTIFYING THE 10-YEAR INCREMENTAL BENEFIT† Day 14 −4.5% Day 30 −5.2% †UACR reductions per 10-year increase in age, calculated at each study timepoint. UACR, urinary albumin-to-creatinine ratio. 20
Slide 29: Quantifying the 10-Year Incremental Benefit
QUANTIFYING THE 10-YEAR INCREMENTAL BENEFIT† Day 14 −4.5% Day 30 −5.2% Day 180 −10.2% †UACR reductions per 10-year increase in age, calculated at each study timepoint. UACR, urinary albumin-to-creatinine ratio. 20
Slide 30: Quantifying the 10-Year Incremental Benefit
QUANTIFYING THE 10-YEAR INCREMENTAL BENEFIT† Day 14 −4.5% Day 30 −5.2% Day 180 −10.2% Day 210 (off drug) −9.8% †UACR reductions per 10-year increase in age, calculated at each study timepoint. UACR, urinary albumin-to-creatinine ratio. 20
Slide 31: Robustness of Age Effect Across Quartiles
ROBUSTNESS OF AGE EFFECT ACROSS QUARTILES† 20 Finerenone + empagliflozin Finerenone Empagliflozin Change in UACR from baseline (%) 0 –20 –40 –60 –80 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 Days since treatment initiation Days since treatment initiation Days since treatment initiatio
Slide 32: Robustness of Age Effect Across Quartiles
ROBUSTNESS OF AGE EFFECT ACROSS QUARTILES† 20 Finerenone + empagliflozin Finerenone Empagliflozin Change in UACR from baseline (%) 0 –20 –40 –60 –80 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 Days since treatment initiation Days since treatment initiation Days since treatment initiatio
Slide 33: Robustness of Age Effect Across Quartiles
ROBUSTNESS OF AGE EFFECT ACROSS QUARTILES† 20 Finerenone + empagliflozin Finerenone Empagliflozin Change in UACR from baseline (%) 0 –20 –40 –60 –80 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 Days since treatment initiation Days since treatment initiation Days since treatment initiatio
Slide 34: Robustness of Age Effect Across Quartiles
ROBUSTNESS OF AGE EFFECT ACROSS QUARTILES† 20 Finerenone + empagliflozin Finerenone Empagliflozin Change in UACR from baseline (%) 0 –20 –40 –60 –80 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 Days since treatment initiation Days since treatment initiation Days since treatment initiatio
Slide 35: Robustness of Age Effect Across Quartiles
ROBUSTNESS OF AGE EFFECT ACROSS QUARTILES† 20 Finerenone + empagliflozin Finerenone Empagliflozin Change in UACR from baseline (%) 0 –20 –40 –60 –80 0 14 30 90 180 210 0 14 30 90 180 210 0 14 30 90 180 210 Days since treatment initiation Days since treatment initiation Days since treatment initiatio
Slide 36: Age Effect Is Independent of Treatment Assignment
AGE EFFECT IS INDEPENDENT OF TREATMENT ASSIGNMENT Age interaction p=0.28 22
Slide 37: Advanced Age Is an Efficacy Multiplier
ADVANCED AGE IS AN EFFICACY MULTIPLIER Key finding Age effect Increasing age is associated with a progressively greater reduction in UACR from baseline at all observed time points p=0.001 Linear effect Findings hold true continuously and by predefined quartiles (p=0.009) UACR, urinary albumin-to-cre
Slide 38: Resolving the Knowledge Gap
RESOLVING THE KNOWLEDGE GAP Primary aim Secondary aim Safety objective Quantify the independent Evaluate baseline clinical effects of age and sex on the Determine if safety profiles characteristics and anti-albuminuric efficacy of (specifically AKI and longitudinal changes in finerenone, hyperkalemi
Slide 39: Safety Profile Maintained Across Demographics
SAFETY PROFILE MAINTAINED ACROSS DEMOGRAPHICS Age quartile 1 Age quartile 4 Safety event, % (youngest) (oldest) 0.0 0.5 AKI No clinically relevant association 13.4 12.0 Hyperkalemia Incidence consistent across age 0.0 0.0 Symptomatic hypotension Rare events AKI, acute kidney injury. 25
Slide 40: Safety Profile Maintained Across Demographics
SAFETY PROFILE MAINTAINED ACROSS DEMOGRAPHICS Age quartile 1 Age quartile 4 Safety event, % (youngest) (oldest) 0.0 0.5 AKI No clinically relevant association 13.4 12.0 Hyperkalemia Incidence consistent across age 0.0 0.0 Symptomatic hypotension Rare events Treatment remains tolerated even as age-re
Slide 41: Visualizing the Efficacy Trajectory
VISUALIZING THE EFFICACY (UACR REDUCTION) TRAJECTORY Age and sex percentiles Males Females UACR, urinary albumin-to-creatinine ratio. 26
Slide 42: Visualizing the Efficacy Trajectory
VISUALIZING THE EFFICACY (UACR REDUCTION) TRAJECTORY Age and sex percentiles Age quartiles (>74 vs ≤60 years) Males ≤60 years >74 years Females UACR, urinary albumin-to-creatinine ratio. 26
Slide 43: Visualizing the Efficacy Trajectory
VISUALIZING THE EFFICACY (UACR REDUCTION) TRAJECTORY Age and sex percentiles Age quartiles (>74 vs ≤60 years) Increment per 10-year greater age (%) Time (day since treatment initiation) Males ≤60 years 14 30 90 180 210 >74 years Females UACR, urinary albumin-to-creatinine ratio. 26
Slide 44: Summary
SUMMARY The combination of empagliflozin and finerenone was beneficial in males and females, and across all ages First evidence identifying clinically meaningful sex differences in UACR response with SGLT2is, finerenone, or their combination in T2D SGLT2i, sodium-glucose cotransporter 2 inhibitor; T
Slide 45: The Lifetime Benefit of Intervention
THE “LIFETIME” BENEFIT OF INTERVENTION Conclusion: Never “too old to treat” Older patients derive enhanced reduction in albuminuria Early onset Late onset Age 50 Age 75 Age 80+ High CVD risk1 CONFIDENCE data: Treating now offers “Magnitude” of response “duration” of protection increases (–10% extra/
Slide 46: Confronting Historical Clinical Paradigms
CONFRONTING HISTORICAL CLINICAL PARADIGMS Revisiting female cardioprotection A paradoxical ~20% greater UACR reduction in females vs males challenges assumptions of biological non-response in females The greater increase in female CV/CKD risk with diabetes likely stems from historical underdia
Slide 47: Mechanistic Interpretation and Hypothesis Generation
MECHANISTIC INTERPRETATION AND HYPOTHESIS GENERATION Sex-specific tubuloglomerular 1 1 feedback sensitivity differences to SGLT2 inhibition1,2 SGLT2, sodium-glucose cotransporter 2. 1. Swapnasrita S, et al. Front Physiol. 2022;13:741121. 2. McDonough AA, et al. Am J Physiol Renal Physiol. 2025;328(5
Slide 48: Mechanistic Interpretation and Hypothesis Generation
MECHANISTIC INTERPRETATION AND HYPOTHESIS GENERATION Sex-specific tubuloglomerular 2 1 1 feedback sensitivity differences to SGLT2 inhibition1,2 2 Differential MR activation patterns SGLT2, sodium-glucose cotransporter 2; MR, mineralocorticoid receptor. 1. Swapnasrita S, et al. Front Physiol. 2022;1
Slide 49: Mechanistic Interpretation and Hypothesis Generation
MECHANISTIC INTERPRETATION AND HYPOTHESIS GENERATION Sex-specific tubuloglomerular 2 1 1 feedback sensitivity differences to SGLT2 inhibition1,2 2 Differential MR activation patterns 3 Estrogen receptor-mediated modulation of 3 albumin receptor trafficking SGLT2, sodium-glucose cotransporter 2; MR,
Slide 50: Mechanistic Interpretation and Hypothesis Generation
MECHANISTIC INTERPRETATION AND HYPOTHESIS GENERATION Sex-specific tubuloglomerular 2 1 1 feedback sensitivity differences to SGLT2 inhibition1,2 2 Differential MR activation patterns 3 Estrogen receptor-mediated modulation of 3 albumin receptor trafficking 4 Sex-chromosome complement 4 effects on tr
Slide 51: Take-Home Messages
TAKE-HOME MESSAGES Additional 10% UACR reduction per decade of increased age UACR, urinary albumin-to-creatinine ratio. 31
Slide 52: Take-Home Messages
TAKE-HOME MESSAGES Additional 10% UACR reduction per decade of increased age Age effect – independent of treatment UACR, urinary albumin-to-creatinine ratio. 31
Slide 53: Take-Home Messages
TAKE-HOME MESSAGES Additional Greater UACR 10% UACR reduction per decade of increased age 20% reduction in females vs males Age effect – independent of treatment UACR, urinary albumin-to-creatinine ratio. 31
Slide 54: Take-Home Messages
TAKE-HOME MESSAGES Additional Greater UACR 10% UACR reduction per decade of increased age 20% reduction in females vs males Age effect – independent Safety profile preserved of treatment with increasing age UACR, urinary albumin-to-creatinine ratio. 31
Slide 55: Thank You to My Co-Authors, Investigators, Staff, and Trial Participants
THANK YOU TO MY CO-AUTHORS, INVESTIGATORS, STAFF, AND TRIAL PARTICIPANTS Co-authors: Jennifer B Green, Hiddo JL Heerspink, Johannes FE Mann, Janet B McGill, Amy K Mottl, Peter Rossing, Julio Rosenstock, Muthiah Vaduganathan, Charlie Scott, Lucas Hofmeister, Na Li, Li Li, and Masaomi Nangaku Ackn
Slide 56: Scan QR Code for the Published Paper
FOR THE PUBLISHED PAPER IN NEPHROLOGY DIALYSIS TRANSPLANTATION , SCAN THIS QR CODE 33