Daily Endocrinology Research Analysis
Three studies advance endocrine and cardiometabolic care: an RCT in NEJM shows that initiating finerenone plus empagliflozin reduces albuminuria more than either drug alone in CKD with type 2 diabetes; a multicenter, double-blind RCT in BMJ demonstrates histologic improvement and fibrosis benefit with dapagliflozin in biopsy-proven MASH; and a first-in-human study introduces [18F]AldoView PET/CT for selective CYP11B2 imaging to noninvasively localize aldosterone-producing lesions.
Summary
Three studies advance endocrine and cardiometabolic care: an RCT in NEJM shows that initiating finerenone plus empagliflozin reduces albuminuria more than either drug alone in CKD with type 2 diabetes; a multicenter, double-blind RCT in BMJ demonstrates histologic improvement and fibrosis benefit with dapagliflozin in biopsy-proven MASH; and a first-in-human study introduces [18F]AldoView PET/CT for selective CYP11B2 imaging to noninvasively localize aldosterone-producing lesions.
Research Themes
- Combination reno-cardiometabolic therapy in diabetic kidney disease
- SGLT2 inhibition as disease-modifying therapy for MASH
- Molecular imaging for CYP11B2 to subtype primary aldosteronism
Selected Articles
1. Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes.
In adults with CKD and type 2 diabetes, initiating finerenone plus empagliflozin produced a 29–32% greater reduction in UACR at 180 days than either agent alone, with no unexpected safety signals. Symptomatic hypotension, AKI, and hyperkalemia leading to discontinuation were uncommon.
Impact: This well-powered RCT directly tests initial combination therapy, demonstrating additive renoprotection on a validated surrogate (albuminuria) with reassuring safety, informing therapeutic strategies in DKD.
Clinical Implications: For patients with CKD and type 2 diabetes with albuminuria, early co-initiation of finerenone and an SGLT2 inhibitor may provide superior antiproteinuric effects compared with monotherapy, pending confirmation on hard renal/cardiovascular outcomes.
Key Findings
- At day 180, UACR reduction was 29% greater versus finerenone alone (ratio 0.71; 95% CI 0.61–0.82; P<0.001).
- At day 180, UACR reduction was 32% greater versus empagliflozin alone (ratio 0.68; 95% CI 0.59–0.79; P<0.001).
- No unexpected adverse events; symptomatic hypotension, AKI, and hyperkalemia leading to discontinuation were uncommon.
- Baseline median UACR was 579 mg/g (IQR 292–1092) among those with available data.
Methodological Strengths
- Randomized, parallel-group trial with prespecified primary endpoint at 180 days
- Clinically relevant population with CKD and type 2 diabetes; trial registered (NCT05254002)
Limitations
- Primary outcome based on surrogate (albuminuria) over a short 180-day horizon
- Hard renal and cardiovascular outcomes not yet reported; details on blinding not specified in abstract
Future Directions: Longer-term trials should evaluate effects on eGFR slope, kidney failure, cardiovascular events, and mortality, and define which patient subgroups derive the greatest benefit from up-front combination therapy.
2. Effect of dapagliflozin on metabolic dysfunction-associated steatohepatitis: multicentre, double blind, randomised, placebo controlled trial.
In biopsy-proven MASH, dapagliflozin significantly increased the proportion achieving MASH improvement without fibrosis worsening (53% vs 30%; RR 1.73) and showed benefits on MASH resolution and fibrosis improvement over 48 weeks. Discontinuations due to adverse events were rare and comparable to placebo.
Impact: This double-blind RCT provides histologic evidence that SGLT2 inhibition can modify disease activity and fibrosis in MASH, addressing a major unmet therapeutic need.
Clinical Implications: Dapagliflozin may be considered in patients with MASH (with or without T2D) to improve steatohepatitis activity and fibrosis, with attention to regulatory guidance and individual risk–benefit; confirms rationale for larger, longer outcome trials.
Key Findings
- MASH improvement without fibrosis worsening: 53% with dapagliflozin vs 30% with placebo (RR 1.73; P=0.006).
- MASH resolution without fibrosis worsening: 23% vs 8% (RR 2.91; P=0.01).
- Fibrosis improvement without MASH worsening: 45% vs 20% (RR 2.25; P=0.001).
- Mean NAS decreased more with dapagliflozin (Δ −1.39; P<0.001); discontinuations due to AEs were low (1% vs 3%).
Methodological Strengths
- Multicenter, double-blind, randomized, placebo-controlled design with biopsy-confirmed MASH
- Intention-to-treat analysis with prespecified histologic endpoints
Limitations
- Moderate sample size (n=154) and 48-week duration; long-term clinical outcomes not assessed
- Single-country study (China) may limit generalizability; mechanistic biomarkers not deeply explored
Future Directions: Confirm efficacy across diverse populations and longer horizons, evaluate effects on decompensation, cirrhosis progression, and mortality, and explore combinatorial regimens and mechanistic correlates.
3. First-in-Human Evaluation of [ 18 F]AldoView: A Highly Selective PET Tracer for Aldosterone Synthase Imaging in Primary Aldosteronism.
[18F]AldoView PET/CT was safe, low-dose, and selectively localized CYP11B2-positive aldosterone-producing lesions, with strong concordance to pathology. No off-target uptake was seen in Cushing’s or nonfunctional adenomas, supporting noninvasive subtyping of primary aldosteronism.
Impact: This first-in-human, target-selective imaging approach could transform diagnostic pathways by reducing reliance on invasive adrenal venous sampling for PA subtyping.
Clinical Implications: If validated, [18F]AldoView may enable accurate, noninvasive localization of aldosterone-producing adenomas/nodules to guide surgery and personalize therapy, potentially reducing invasive testing.
Key Findings
- No adverse events; effective dose 0.012±0.0022 mSv/MBq indicating a favorable dosimetry profile.
- All 10 PA patients with positive scans had high uptake (mean SUVmax 15.73; LAR 8.02; LLR 10.24) and strong CYP11B2 staining confirming APA/APN.
- No positive uptake in idiopathic hyperaldosteronism, Cushing’s syndrome, or nonfunctional adenomas, suggesting high target specificity.
Methodological Strengths
- Prospective first-in-human feasibility with predefined positivity criteria and quantitative SUV metrics
- Pathology correlation of resected lesions confirming CYP11B2 expression; inclusion of healthy volunteers for dosimetry
Limitations
- Small sample size and ongoing study; limited external validation and no head-to-head comparison with adrenal venous sampling
- Potential selection and verification biases; short imaging time point (60 minutes) without dynamic characterization
Future Directions: Conduct larger, multicenter diagnostic accuracy studies against adrenal venous sampling, assess interreader reliability, and evaluate impact on clinical decision-making and outcomes.