Daily Endocrinology Research Analysis
Three impactful endocrinology-related studies advanced diagnostics and outcomes research. A multicenter prospective validation showed plasma metabolite signatures outperform CA19-9 for excluding pancreatic ductal adenocarcinoma in high-risk cohorts. A novel 18F-exendin-4 GLP-1 receptor PET/CT achieved 100% sensitivity for insulinoma localization, and a meta-analysis associated SGLT2 inhibitors with fewer major adverse liver-related outcomes in type 2 diabetes.
Summary
Three impactful endocrinology-related studies advanced diagnostics and outcomes research. A multicenter prospective validation showed plasma metabolite signatures outperform CA19-9 for excluding pancreatic ductal adenocarcinoma in high-risk cohorts. A novel 18F-exendin-4 GLP-1 receptor PET/CT achieved 100% sensitivity for insulinoma localization, and a meta-analysis associated SGLT2 inhibitors with fewer major adverse liver-related outcomes in type 2 diabetes.
Research Themes
- Noninvasive endocrine-pancreas diagnostics
- Cardiometabolic therapies with hepatic outcome benefits
- Translational molecular imaging targeting GLP-1 receptors
Selected Articles
1. Validation of two plasma multimetabolite signatures for patients at risk of or with suspected pancreatic ductal adenocarcinoma (METAPAC): a prospective, multicentre, investigator-masked, enrichment design, phase 4 diagnostic study.
In a prospective, multicenter, investigator-masked phase 4 study (n=1129), two plasma metabolite signatures (i-Metabolic, m-Metabolic) outperformed CA19-9 in excluding pancreatic ductal adenocarcinoma at high specificity (i-Metabolic AUC 0.846; specificity 90.4%; sensitivity 67.5). The minimalistic signature maintained high specificity (93.6%) with moderate sensitivity and also discriminated incident PDAC in new-onset diabetes. Performance was stable across simulated prevalence.
Impact: Provides validated, generalizable, noninvasive biomarkers to streamline diagnostic pathways in high-risk patients, potentially reducing invasive procedures and enabling earlier resectable detection.
Clinical Implications: In patients with pancreatic lesions or high annual PDAC risk (including new-onset diabetes), plasma metabolite signatures could complement imaging to exclude malignancy with high specificity, prioritizing surveillance and reducing unnecessary invasive workups.
Key Findings
- Prospective validation in 1129 patients showed i-Metabolic signature AUC 0.846, specificity 90.4%, sensitivity 67.5, outperforming CA19-9 (AUC 0.799).
- Minimalistic m-Metabolic signature achieved AUC 0.846 with specificity 93.6% and sensitivity 59.9%.
- In a new-onset diabetes subgroup (n=242; 3 incident PDAC), the m-Metabolic signature (without CA19-9) significantly discriminated PDAC (p=0.038).
Methodological Strengths
- Prospective, multicenter, investigator-masked design with surgical/pathologic verification.
- Predefined signatures tested in a real-world enriched cohort with stability analyses across prevalence.
Limitations
- Balanced accuracy gains were driven by higher specificity with moderate sensitivity; clinical thresholds need calibration.
- Single-country cohort; external validation in diverse populations and health systems is needed.
Future Directions: External validation across ethnogeographic cohorts, health-economic impact studies, and integration with imaging/risk models to create triage algorithms for high-risk surveillance and workup.
2. Qualitative and Quantitative Analyses of Noninvasive Diagnosis of Insulinoma Using [18F]FB(ePEG12) 12-Exendin-4 PET/CT.
In a prospective single-center phase 2 interim study of 12 patients with hyperinsulinemic hypoglycemia, 18F-exendin-4 GLP-1 receptor PET/CT localized insulinomas with 100% sensitivity, exceeding CT (83%), MRI (63%), endoscopic ultrasonography (90%), and selective arterial calcium stimulation (89%). All lesions were surgically confirmed and hypoglycemia resolved after resection.
Impact: Demonstrates a highly sensitive, noninvasive functional imaging modality targeting GLP-1 receptors, addressing a critical gap in preoperative localization of insulinoma.
Clinical Implications: 18F-exendin-4 PET/CT may become a first-line or adjunct diagnostic tool for suspected insulinoma, potentially reducing reliance on invasive localization procedures and improving surgical planning.
Key Findings
- 18F-exendin-4 PET/CT achieved 100% sensitivity in detecting insulinomas (12/12), surpassing CT (83%), MRI (63%), EUS (90%), and SACST (89%).
- Significantly higher tracer uptake in tumors than surrounding pancreas enabled clear localization at 60 and 120 minutes.
- All lesions were surgically confirmed insulinomas with complete resolution of hypoglycemia post-resection.
Methodological Strengths
- Prospective design with surgical/pathologic gold-standard verification.
- Head-to-head comparison with multiple conventional modalities in real clinical workflow.
Limitations
- Small sample size (n=12), single-center interim report limits generalizability.
- Specificity and negative predictive value could not be robustly assessed in this enriched cohort.
Future Directions: Multicenter phase 3 diagnostic accuracy trials with larger, unselected cohorts and standardized thresholds; comparative effectiveness and cost-effectiveness vs invasive localization.
3. Sodium-Glucose Cotransporter 2 Inhibitor Use and Risk of Liver-Related Events in Patients With Type 2 Diabetes: A Meta-analysis of Observational Cohort Studies.
Across eight new-user, active-comparator cohort studies including 626,104 adults with type 2 diabetes (median follow-up 2.7 years), SGLT2 inhibitor initiation was associated with lower risk of major adverse liver-related outcomes (HR 0.83; 95% CI 0.72–0.95) and liver-related deaths (HR 0.64; 0.50–0.82). Benefits were consistent vs DPP-4 inhibitors, metformin, or pioglitazone but not GLP-1 receptor agonists; heterogeneity for MALOs was high (I2=83%).
Impact: Provides large-scale, consistent observational evidence that SGLT2 inhibitors may confer hepatic benefits beyond glycemic control in T2D, informing cardiometabolic-liver risk reduction strategies.
Clinical Implications: When selecting glucose-lowering therapy for T2D, SGLT2 inhibitors may be preferred in patients at risk for liver-related complications; clinicians should still individualize choices and recognize residual confounding and heterogeneity.
Key Findings
- Meta-analysis of 8 cohort studies (n=626,104) found SGLT2 inhibitors associated with reduced MALOs (HR 0.83) and liver-related deaths (HR 0.64).
- Risk reduction consistent versus DPP-4 inhibitors, metformin, and pioglitazone but not versus GLP-1 receptor agonists.
- No significant publication bias; high heterogeneity for composite MALOs (I2=83.1%).
Methodological Strengths
- Active-comparator new-user designs reduce confounding by indication.
- Large aggregate sample size with consistent sensitivity analyses and funnel plot assessment.
Limitations
- Observational evidence with residual confounding; high heterogeneity across studies.
- Outcome definitions and covariate adjustments vary; lack of RCT confirmation.
Future Directions: Pragmatic randomized trials and target-trial emulations focusing on hepatic endpoints; mechanistic studies to clarify pathways of hepatoprotection with SGLT2 inhibition.