Weekly Endocrinology Research Analysis
This week’s endocrinology literature was dominated by translational advances that could change screening, diagnosis, and treatment pathways. A validated miRNA-based dynamic risk score (Nature Medicine) promises earlier, generalizable stratification for type 1 diabetes and prediction of therapeutic response. Large randomized and pragmatic trials (Lancet Diabetes & Endocrinology; NEJM) support simplified once‑weekly fixed‑ratio insulin–GLP‑1RA regimens and additive renoprotective benefit from fine
Summary
This week’s endocrinology literature was dominated by translational advances that could change screening, diagnosis, and treatment pathways. A validated miRNA-based dynamic risk score (Nature Medicine) promises earlier, generalizable stratification for type 1 diabetes and prediction of therapeutic response. Large randomized and pragmatic trials (Lancet Diabetes & Endocrinology; NEJM) support simplified once‑weekly fixed‑ratio insulin–GLP‑1RA regimens and additive renoprotective benefit from finerenone plus SGLT2 inhibition, respectively. Together these studies push toward biomarker‑guided, less burdensome regimens and upfront combination strategies in high‑risk cardio‑renal‑metabolic disease.
Selected Articles
1. A microRNA-based dynamic risk score for type 1 diabetes.
Multicontext multicenter cohorts identified 50 miRNAs linked to beta‑cell functional loss and produced an externally validated, AI‑enhanced dynamic risk score (DRS) that stratified type 1 diabetes risk (AUC 0.84) and predicted therapeutic response (e.g., imatinib responders) and post‑islet transplantation insulin requirement.
Impact: Provides a validated, generalizable molecular biomarker panel and AI workflow that can enable earlier identification of high‑risk individuals and prediction of treatment response, representing a potential paradigm shift in T1D screening and trial enrichment.
Clinical Implications: Supports implementation studies for risk‑based screening and triage to disease‑modifying therapies; could refine candidacy for interventions (immune therapies, islet transplantation) and monitoring strategies when assay standardization and cost‑effectiveness are established.
Key Findings
- Identified 50 miRNAs associated with functional β‑cell loss and built a multicontext miRNA DRS (development n=2,204; validation n=662) achieving AUC 0.84.
- The baseline miRNA signature predicted therapeutic responders (imatinib trial) and future exogenous insulin requirement after islet transplantation.
2. Once‑weekly IcoSema versus once‑weekly insulin icodec in type 2 diabetes management (COMBINE 1): an open‑label, multicentre, treat‑to‑target, randomised, phase 3a trial.
In a 52‑week, global, treat‑to‑target phase 3a RCT (n=1,291), once‑weekly IcoSema (fixed ratio insulin icodec + semaglutide) produced superior HbA1c reduction versus once‑weekly icodec alone, supporting efficacy of a simplified weekly fixed‑ratio insulin–GLP‑1RA co‑formulation for insulin‑treated type 2 diabetes.
Impact: Demonstrates that once‑weekly fixed‑ratio insulin–GLP‑1RA can outperform weekly basal insulin alone, potentially simplifying intensification strategies and reducing injection burden in insulin‑treated T2D.
Clinical Implications: For patients inadequately controlled on daily basal insulin, once‑weekly IcoSema may be considered to achieve superior glycemic control with fewer injections; clinicians should weigh safety, hypoglycemia, weight effects, and cost in individual decisions.
Key Findings
- 52‑week, open‑label, treat‑to‑target RCT across 192 sites in 20 countries (n=1,291).
- IcoSema achieved statistically superior HbA1c reduction versus weekly icodec at week 52.
3. Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes.
In a randomized trial (CONFIDENCE, n=784), initial co‑initiation of finerenone plus empagliflozin produced a 29–32% greater reduction in urinary albumin‑to‑creatinine ratio at 180 days versus either agent alone, without new safety signals, indicating additive antiproteinuric benefit from early combination therapy in diabetic kidney disease.
Impact: Provides randomized evidence that upfront MR antagonist plus SGLT2 inhibitor therapy yields additive surrogate renoprotection, informing clinicians about potential benefits of early combination strategies in DKD.
Clinical Implications: Consideration of early co‑initiation of finerenone and an SGLT2 inhibitor in patients with DKD and albuminuria may be warranted to maximize antiproteinuric effects; longer‑term data on hard renal and CV outcomes remain necessary.
Key Findings
- At day 180, UACR reduction with combination therapy was 29% greater vs finerenone alone (ratio 0.71; 95% CI 0.61–0.82) and 32% greater vs empagliflozin alone (ratio 0.68; 95% CI 0.59–0.79).
- No unexpected adverse events; symptomatic hypotension, AKI, and hyperkalemia leading to discontinuation were uncommon.