Daily Endocrinology Research Analysis
Across endocrinology, three studies stand out for immediate practice impact: a multi–health system comparative effectiveness analysis shows GLP-1 receptor agonists confer the greatest protection against major cardiovascular events in type 2 diabetes, followed by SGLT2 inhibitors. A large retrospective cohort defines actionable early-morning cortisol cutoffs to safely discontinue glucocorticoids without short synacthen testing. A nationwide cohort links adolescent autoimmune disorders—especially
Summary
Across endocrinology, three studies stand out for immediate practice impact: a multi–health system comparative effectiveness analysis shows GLP-1 receptor agonists confer the greatest protection against major cardiovascular events in type 2 diabetes, followed by SGLT2 inhibitors. A large retrospective cohort defines actionable early-morning cortisol cutoffs to safely discontinue glucocorticoids without short synacthen testing. A nationwide cohort links adolescent autoimmune disorders—especially autoimmune thyroid disease and celiac disease—to markedly higher incident type 1 diabetes risk in adulthood.
Research Themes
- Cardiovascular outcome differences across glucose-lowering drug classes in type 2 diabetes
- Biomarker-based pathways to streamline glucocorticoid weaning
- Autoimmunity as a predictor of incident type 1 diabetes
Selected Articles
1. Glucose-Lowering Medication Classes and Cardiovascular Outcomes in Patients With Type 2 Diabetes.
In a 4-arm trial emulation across 241,981 adults with T2D, sustained treatment with GLP-1 receptor agonists yielded the lowest 2.5-year MACE risk, followed by SGLT2 inhibitors, sulfonylureas, and DPP-4 inhibitors. Benefits of GLP-1 receptor agonists over SGLT2 inhibitors were most evident in older patients and those with ASCVD, heart failure, or mild-moderate CKD.
Impact: Provides robust, head-to-head comparative effectiveness using advanced causal methods to guide class selection for cardiovascular risk reduction in T2D.
Clinical Implications: For patients with T2D, prioritize GLP-1 receptor agonists for MACE risk reduction, especially in older adults and those with ASCVD/HF or CKD; SGLT2 inhibitors remain a strong alternative. Individualize decisions by comorbidity, access, cost, and extra-cardiometabolic benefits.
Key Findings
- 2.5-year MACE risk was lowest with GLP-1RAs, followed by SGLT2is, sulfonylureas, and DPP-4is.
- Risk difference favored GLP-1RAs over SGLT2is by 1.5% (95% CI 1.1–1.9%) and sulfonylureas over DPP-4is by 1.9% (1.1–2.7%).
- GLP-1RA advantage was strongest in patients ≥65 years, or with baseline ASCVD, heart failure, or low-to-moderate kidney impairment; not evident in patients <50 years.
- Trial emulation with targeted learning across 6 US health systems strengthened causal inference from routine care data.
Methodological Strengths
- Large multi-system new-user cohort with trial emulation and targeted learning
- Pre-specified heterogeneity of treatment effects analyses across key subgroups
Limitations
- Observational design susceptible to residual confounding and exposure misclassification
- Sustained exposure definitions and adherence may vary across systems
Future Directions: Pragmatic head-to-head RCTs and emulations with richer phenotyping and cost-effectiveness to refine class sequencing by patient phenotype.
2. Thyroid, Celiac, and Other Autoimmune Diseases and the Risk of Incident Type 1 Diabetes in Young Adulthood.
In a cohort of 1.43 million Israeli adolescents, preexisting autoimmunity conferred a >2-fold increased risk of incident adult-onset type 1 diabetes. Risks were especially high with autoimmune thyroid disease (≈4-fold) and celiac disease (≈3-fold), consistent across sensitivity analyses requiring islet autoantibodies.
Impact: Defines population-level future T1D risk associated with common autoimmune disorders, enabling targeted surveillance and prevention strategies.
Clinical Implications: Adolescents with autoimmune thyroid disease or celiac disease warrant proactive education, periodic glycemic monitoring, and consideration of islet autoantibody testing and trial enrollment for T1D prevention.
Key Findings
- Among 1,426,362 adolescents, any autoimmunity doubled adult-onset T1D risk (HR 2.19, 95% CI 1.57–3.04).
- Autoimmune thyroid disease and celiac disease conferred markedly elevated risks (HR 3.99 and 2.82, respectively).
- Findings were robust in analyses requiring islet autoantibodies for T1D definition (HR 2.22).
- Over 15.8 million person-years of follow-up, crude incidence was 9.6 vs 4.8 per 10^5 person-years with and without autoimmunity.
Methodological Strengths
- Nationwide cohort with registry linkage and >15 million person-years
- Adjusted Cox models with sensitivity analyses using islet autoantibody-confirmed T1D
Limitations
- Observational design with potential unmeasured confounding
- Findings from a single national system may limit generalizability to other populations
Future Directions: Integrate risk stratification into adolescent clinics for autoimmunity, evaluate cost-effectiveness of surveillance, and test prevention strategies in high-risk groups.
3. Diagnostic performance of morning serum cortisol for glucocorticoid weaning in children and adults.
In 523 SSTs across pediatric and adult cohorts, early-morning cortisol predicted SST outcomes well (AUC 0.79 pediatric, 0.88 adult). An adult EMC >290 nmol/L provided a practical threshold to safely discontinue glucocorticoids with high sensitivity, with 48/51 adults in the 290–349 nmol/L band successfully weaned without adverse events.
Impact: Offers actionable cortisol cutoffs to streamline glucocorticoid weaning and reduce need for SST, spanning both pediatric and adult populations with modern assays.
Clinical Implications: In adults weaning from glucocorticoids, consider stopping therapy when EMC >290 nmol/L with appropriate clinical oversight; reserve SST for equivocal ranges and pediatrics as per local pathways.
Key Findings
- EMC predicted SST outcomes with AUC 0.88 (adults) and 0.79 (pediatrics).
- Adult EMC cutoffs: 290 nmol/L (95% sensitivity) and 349 nmol/L (99% sensitivity) for predicting SST pass (≥430 nmol/L at 30 min).
- In adults with EMC 290–349 nmol/L, 48/51 were successfully weaned off glucocorticoids without adverse events.
- Pediatric EMC thresholds were 278 and 316 nmol/L for 95% and 99% sensitivity, respectively.
Methodological Strengths
- Large retrospective cohort spanning pediatric and adult populations
- ROC-based cutoffs using modern immunoassays with validation in clinical weaning outcomes
Limitations
- Retrospective design and potential selection bias in who underwent SST
- Generalizability across assays and centers may vary; pediatric operationalization requires care
Future Directions: Prospective validation across platforms and integration into steroid-weaning protocols with clinical decision support to reduce unnecessary SST.