Daily Endocrinology Research Analysis
Three impactful endocrinology papers stand out today: a multi-cohort analysis supports 1-hour plasma glucose as a superior diagnostic marker for type 2 diabetes, a meta-analysis of randomized trials shows advanced diabetes technologies improve safety and glycemic control in older adults with type 1 diabetes, and a large target-trial emulation finds pre-transplant dual GLP-1RA plus SGLT2 inhibitor therapy is associated with lower 12-month mortality after solid-organ transplantation.
Summary
Three impactful endocrinology papers stand out today: a multi-cohort analysis supports 1-hour plasma glucose as a superior diagnostic marker for type 2 diabetes, a meta-analysis of randomized trials shows advanced diabetes technologies improve safety and glycemic control in older adults with type 1 diabetes, and a large target-trial emulation finds pre-transplant dual GLP-1RA plus SGLT2 inhibitor therapy is associated with lower 12-month mortality after solid-organ transplantation.
Research Themes
- Modernizing diabetes diagnosis with 1-hour oral glucose tolerance testing
- Safety and efficacy of advanced diabetes technologies in older adults
- Pre-transplant metabolic optimization with dual incretin–SGLT2 therapy
Selected Articles
1. Superiority of 1 h plasma glucose vs fasting plasma glucose, 2 h plasma glucose and HbA
Across five independent cohorts, 1-hour plasma glucose consistently achieved higher diagnostic AUCs, with superior sensitivity and specificity compared with fasting glucose, 2-hour glucose, and HbA1c combinations. These results reinforce the IDF proposal to adopt 1-hour glucose as a diagnostic tool for type 2 diabetes.
Impact: Demonstrating superior diagnostic performance across multiple populations positions 1-hour glucose testing to modernize and potentially streamline type 2 diabetes diagnosis.
Clinical Implications: Clinicians and health systems should consider integrating 1-hour OGTT sampling into diagnostic pathways, with work to define optimal thresholds, workflows, and cost-effectiveness to enable broader implementation.
Key Findings
- In KoGES, 1 h PG achieved AUC 0.96 vs 0.88 for FPG+HbA1c, with higher sensitivity (84.2% vs 77.0%) and specificity (98.6% vs 87.0%).
- In PLIS follow-up, 1 h PG delivered AUC 0.98 vs 0.76, sensitivity 94.9% vs 46.8%, and specificity 100% vs 92.3% compared with FPG+HbA1c.
- Consistent superiority of 1 h PG was observed across CATAMERI, GENFIEV, and TULIP follow-up cohorts, supporting the IDF recommendation.
Methodological Strengths
- Multi-cohort analysis across five independent populations with consistent ROC-based results
- Direct head-to-head comparison of 1 h PG versus FPG, 2 h PG, and HbA1c metrics
Limitations
- Diagnostic analyses are observational and cross-sectional; prospective validation for thresholds and workflows is needed
- Operational burden of OGTT-based sampling and need for standardized 1 h PG cutoffs were not addressed in the abstract
Future Directions: Prospective, pragmatic studies to define standardized 1 h PG thresholds, assess implementation logistics, and evaluate cost-effectiveness and health equity impacts.
2. Impact of stepwise diabetes technology advances in older adults with type 1 diabetes: A systematic review and meta-analysis of randomised trials.
In older adults with long-standing type 1 diabetes, upgrading to automated insulin delivery or continuous glucose monitoring increased time-in-range and reduced time-below-range, with a marked reduction in severe hypoglycemia and no significant increase in DKA.
Impact: High-quality synthesis of RCTs focused on an often underrepresented population provides actionable evidence to expand safe use of advanced diabetes technologies in older adults.
Clinical Implications: Age alone should not preclude prescribing AID or CGM for older adults; clinicians can expect improved glycemic metrics and fewer severe hypoglycemic events while maintaining DKA safety with appropriate selection and support.
Key Findings
- Higher-level technologies increased time-in-range by +7.90% (95% CI 7.09 to 8.72) and reduced TBR <3.9 mmol/L by -0.62% (95% CI -1.02 to -0.22).
- Severe hypoglycemia risk was substantially lower (Peto OR 0.16, 95% CI 0.06 to 0.41; NNT ≈ 20), with no significant rise in DKA (Peto OR 3.72, p=0.11).
- Benefits extended to reductions in time-above-range, HbA1c, and glycemic variability across trials.
Methodological Strengths
- Meta-analysis restricted to randomized controlled trials with prespecified co-primary outcomes
- Included both crossover and parallel designs in older adults (≥60–65 years), enhancing applicability to geriatric care
Limitations
- Total sample size (n=482) remains modest and trial durations are relatively short
- Crossover designs may introduce carryover effects; technology training intensity could influence outcomes
Future Directions: Longer-term RCTs and pragmatic trials in diverse health systems to assess durability of benefits, fall risk, cognitive impacts, quality of life, and implementation equity.
3. Effectiveness of Pre-Transplant Dual GLP-1 Receptor Agonist and SGLT2 Inhibitor Therapy on All-Cause Mortality in Organ Transplantation Candidates with Obesity and Type 2 Diabetes: a Target-Trial Emulation.
In a large target-trial emulation using US EHR data, pre-transplant dual GLP-1RA plus SGLT2 inhibitor therapy in obese adults with type 2 diabetes was associated with significantly lower 12-month all-cause mortality versus GLP-1RA or SGLT2i monotherapy and usual care, with neutral or reduced infections and consistent sensitivity analyses.
Impact: This study identifies a potentially practice-changing pre-transplant metabolic strategy associated with lower post-transplant mortality across multiple comparators, using rigorous emulation and large-scale real-world data.
Clinical Implications: Transplant programs may consider structured pre-transplant optimization with combined GLP-1RA and SGLT2i in obese adults with type 2 diabetes, while awaiting prospective trials to confirm causality and refine safety protocols.
Key Findings
- Dual GLP-1RA+SGLT2i therapy was associated with lower 12-month mortality vs GLP-1RA (HR 0.69, 95% CI 0.57–0.85), vs SGLT2i (HR 0.59, 95% CI 0.48–0.72), and vs usual care (HR 0.52, 95% CI 0.43–0.64).
- Infection-related endpoints were neutral or reduced with dual therapy compared with comparators.
- Findings were robust across sensitivity analyses, including landmarking and 24–36 month extensions.
Methodological Strengths
- Target-trial emulation with large EHR network (TriNetX) and 1:1 propensity-score matching across three comparator cohorts
- Multiple sensitivity analyses (global network, landmark, extended follow-up) support robustness
Limitations
- Observational emulation cannot eliminate residual confounding or confounding by indication
- Medication adherence, dosing, and perioperative management details are limited in EHR data
Future Directions: Prospective randomized trials testing pre-transplant dual therapy, organ-specific subgroup analyses, and safety surveillance for perioperative events.