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.
AIMS/HYPOTHESIS: The IDF has proposed 1 h plasma glucose (1 h PG) as a diagnostic test for type 2 diabetes. This study evaluated the utility of 1 h PG in diagnosing type 2 diabetes, compared with fasting plasma glucose (FPG), 2 h plasma glucose (2 h PG), HbA METHODS: Analyses were conducted using data from five independent cohorts: KoGES, CATAMERI, GENFIEV, PLIS (follow-up) and TULIP (follow-up). Type 2 diabetes was defined according to ADA criteria (FPG ≥7.0 mmol/l [≥126 mg/dl], 2 h PG ≥11.1 mmol/l [≥200 mg/dl] or HbA RESULTS: Cohort-specific analyses demonstrated consistently higher AUCs for 1 h PG in KoGES (AUC 0.96 vs 0.88; Δ 0.08; sensitivity 84.2 vs 77.0; specificity 98.6 vs 87.0), CATAMERI (AUC 0.98 vs 0.86; Δ 0.12; sensitivity 75.0 vs 69.4; specificity: 98.4 vs 78.9), GENFIEV (AUC 0.97 vs 0.89; Δ 0.08; sensitivity 89.5 vs 69.4; specificity 100.0 vs 88.3), PLIS follow-up (AUC 0.98 vs 0.76; Δ 0.22; sensitivity 94.9 vs 46.8; specificity 100.0 vs 92.3) and TULIP follow-up (AUC 0.98 vs 0.83; Δ 0.15; sensitivity 90.2 vs 90.2; specificity 100.0 vs 65.0) compared with FPG plus HbA CONCLUSIONS/INTERPRETATION: These findings support the superior utility of the IDF-recommended 1 h PG vs FPG, 2 h PG, HbA
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.
OBJECTIVES: To evaluate the efficacy and safety of advancing to higher levels of diabetes technology in older adults with type 1 diabetes (T1D). METHODS: Web of Science, PubMed, Cochrane Library, and SCOPUS were searched. Inclusion criteria were randomised controlled trials (RCTs); aged ≥60 years with T1D. Interventions were pre-specified into two domain comparisons: (1) Higher-level insulin delivery (defined as automated insulin delivery, AID) versus lower-level insulin delivery (comprising sensor-augmented pumps and predictive low-glucose suspend); and (2) Higher-level glucose monitoring (defined as continuous glucose monitoring, CGM) versus lower-level glucose monitoring (self-monitoring of blood glucose). Co-primary efficacy outcomes were time-below-range of <3.9 mmol/L(TBR3.9) and time-in-range of 3.9-10.0 mmol/L (TIR). Safety outcomes were episodes of diabetic ketoacidosis (DKA) and severe hypoglycemia (SH). RESULTS: Five RCTs (comprising six comparisons) with 482 participants were included. Three trials enrolled participants aged ≥60 years, and two trials enrolled those aged ≥65 years. Three crossover trials contributed to the AID comparison, and two parallel to the CGM comparison. The mean age was 69.2 years, with a mean T1D duration of 36.1 years. In the pooled analysis, higher-level technologies significantly increased TIR (MD = +7.90%, 95% CI: 7.09 to 8.72, p <0.001) and reduced TBR3.9 (MD = -0.62%, 95% CI: -1.02 to -0.22, p = 0.002). Benefits were also observed for TBR <3.0 mmol/L, time-above-range >10.0 and >13.9 mmol/L, HbA1c, and glycemic variability (all p <0.05). Critically, SH risk was markedly lower with higher-level technologies (Peto OR = 0.16, 95% CI: 0.06 to 0.41, p <0.001; number-needed-to-treat = 20), without a significant increase in DKA risk (Peto OR = 3.72, 95% CI: 0.75 to 18.49, p = 0.11). CONCLUSIONS: Advancing to higher-level technologies for glucose monitoring and insulin delivery significantly and safely improve glycemic control in older adults with T1D. Physiological age alone should not be a primary barrier to prescribing these technologies, particularly for carefully selected older adults.
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.
Evidence on pre-transplant metabolic therapy remains limited. We evaluated whether concurrent glucagon-like peptide-1 receptor agonist (GLP-1 RA) plus sodium-glucose cotransporter 2 inhibitor (SGLT2i) use before solid-organ transplantation is was associated with post-transplant outcomes in adults with obesity and type 2 diabetes. A target trial is emulated using de-identified electronic health records from TriNetX US. Dual therapy is compared with GLP-1 RA, SGLT2i, and usual care using 1:1 propensity-score matching. The primary outcome is all-cause mortality at 12 months; kidney graft failure, rejection, complications, and infections are secondary. Sensitivity analyses included the global network, landmark, extensions at 24 and 36 months. Three matched cohorts are constructed, dual versus GLP-1 RA (n = 4718 pairs), dual versus SGLT2i (n = 4282), and dual versus usual care (n = 3787). At 12 months, dual therapy is associated with lower mortality versus GLP-1 RA (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.57-0.85), SGLT2i (0.59, 0.48-0.72), and usual care (0.52, 0.43-0.64). Infection endpoints are neutral or lower. Estimates are consistent across sensitivity analyses. In transplant candidates with obesity and type 2 diabetes, pre-transplant GLP-1 RA+SGLT2i use is associated with lower mortality than monotherapy or usual care. Prospective evaluation is warranted.