Daily Endocrinology Research Analysis
Analyzed 108 papers and selected 3 impactful papers.
Summary
Analyzed 108 papers and selected 3 impactful articles.
Selected Articles
1. Incretins Predict Response to Enteral Nutrition Strategies in the EDEN Trial: A Secondary Analysis.
In a secondary analysis of the EDEN RCT, pre-intervention GIP significantly predicted heterogeneity of treatment effect between trophic and full enteral nutrition: patients in the highest GIP tertile had lower 60-day mortality with trophic feeding. GLP-1 and ARDS subphenotypes did not predict response.
Impact: This is a rigorous biomarker-driven precision nutrition signal within an RCT framework, identifying GIP as a candidate predictor to individualize feeding strategies in ARDS.
Clinical Implications: GIP measurement before initiating enteral nutrition could help stratify ARDS patients for trophic versus full feeding, pending prospective validation.
Key Findings
- Pre-intervention GIP predicted heterogeneity of treatment effect between trophic and full enteral nutrition (interaction p=0.01).
- In the highest GIP tertile, trophic feeding had lower 60-day mortality than full feeding (14.1% vs 27.2%).
- GLP-1 levels, ARDS subphenotypes, and baseline mortality risk did not predict differential response.
Methodological Strengths
- Secondary analysis leveraging randomized treatment assignment from an RCT (EDEN).
- Pre-intervention biomarker assessment with multivariable interaction modeling adjusted for key confounders.
Limitations
- Post hoc secondary analysis; findings require external validation before clinical implementation.
- Biomarker thresholds and assay standardization for GIP are not yet established for bedside use.
Future Directions: Prospective, biomarker-stratified trials to validate GIP-guided feeding strategies and to evaluate mechanistic links between incretins and enteral tolerance.
RATIONALE: The Early versus Delayed Enteral Nutrition (EDEN) trial found no significant difference in mortality between trophic and full enteral nutrition strategies in acute respiratory distress syndrome (ARDS) patients. Heterogeneity of treatment effect (HTE) has been identified in prior ARDS trials. We previously identified intestine-derived incretin hormones (glucose-dependent insulinotropic peptide [GIP] and glucagon-like peptide [GLP]-1 as potential predictive biomarkers in the response to nutrition. OBJECTIVES: To investigate incretins as biomarkers predictive of HTE in EDEN. METHODS: GIP, GLP-1, and host immune response biomarkers were measured from pre-intervention EDEN plasma samples. We investigated HTE with 60-day mortality as a primary outcome by testing interaction of treatment with circulating incretin levels in analyses adjusted for demographics, severity of illness, diabetes mellitus, and circulating interleukin-6, and assessed mortality by treatment arm across incretin tertiles. We additionally tested for HTE by de novo ARDS subphenotypes and by risk of mortality. MEASUREMENTS & MAIN RESULTS: 889 participants were included (452 randomized to trophic and 437 to full enteral nutrition). GIP predicted HTE to enteral nutrition strategies (adjusted interaction p-value 0.01) with lower mortality from trophic feeds (14.1% vs 27.2% in full) in patients in the highest GIP tertile but similar mortality in other tertiles. GLP-1, ARDS subphenotypes, and baseline risk of mortality did not predict HTE. CONCLUSIONS: GIP was unique among incretins in predicting HTE to enteral nutrition strategies in EDEN. Further studies are needed to validate our findings as GIP might serve as a biomarker to guide level of enteral nutrition for ARDS patients.
2. US race/ethnic disparities in diabetes technologies: a systematic review and meta-analysis of 950 000 individuals.
Across 18 US studies with 955,556 individuals, Black/African American and Hispanic people were substantially less likely than Non-Hispanic Whites to use CGM and insulin pumps, while Asians had similar CGM use. Findings underscore persistent disparities in diabetes technology adoption.
Impact: This large, methodologically rigorous synthesis quantifies inequities in CGM and CSII uptake, providing targets for policy and health system interventions to improve equitable access.
Clinical Implications: Health systems should implement equity-focused strategies (coverage expansion, culturally tailored education, device training, and proactive outreach) to close technology gaps and improve outcomes.
Key Findings
- Black/African American and Hispanic individuals had markedly lower odds of CGM use versus Non-Hispanic Whites (OR 0.47 and 0.59, respectively).
- Insulin pump (CSII) use was also lower among Black/African American (OR 0.31) and Hispanic (OR 0.48) populations.
- Asian participants had comparable CGM use to Non-Hispanic Whites; subgroup data for CSII were insufficient.
Methodological Strengths
- PRISMA-registered systematic review with large aggregated sample (≈955,000) and three-level random-effects meta-analysis.
- Subgroup analyses across age groups and diabetes types to probe robustness.
Limitations
- Moderate to substantial heterogeneity and reliance on EMR/administrative data may introduce misclassification and residual confounding.
- Predominance of adult populations limits generalizability to pediatric cohorts.
Future Directions: Prospective implementation studies to test equity-promoting interventions and policy levers that increase CGM/CSII uptake in underrepresented groups.
PURPOSE: To provide a descriptive summary and to quantitatively examine racial and ethnic disparities in the use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) among people living with diabetes in the United States. RESEARCH DESIGN AND METHODS: We followed the Cochrane and PRISMA guidelines (PROSPERO: CRD420251124678). Search was conducted on PubMed, Embase, and Cochrane up to August 2025. Observational studies were included if they (1) were conducted in the United States, (2) evaluated the use of CGM/CSII across different races/ethnic groups, and (3) reported odds ratios (ORs) for between-group comparisons. Three-level random-effect meta-analyses examined OR in the use of CGM/CSII across different groups: Non-Hispanic White (NHW; reference group) vs Black/African American, Hispanic, Asian, and Other. Subgroup analyses were conducted for children vs adults, and type 1 vs type 2 diabetes. RESULTS: Totally, 1737 studies were screened, and 18 studies were included (N = 955 556 individuals). Most participants were NHW (70.9%). Approximately 40% of individuals had type 2 diabetes, and 98.9% were adults. Black/African Americans (OR = 0.47, 95% CI = 0.38-0.60), Hispanics (OR = 0.59, 95% CI = 0.50-0.69), and "Other" (OR = 0.69, 95% CI = 0.58-0.83) were less likely to use CGM, relative to NHW individuals, while Asians were equally likely. Black/African Americans (OR = 0.31, 95% CI = 0.23-0.42) and Hispanics (OR = 0.48, 95% CI = 0.42-0.55) were less likely to use a CSII when compared to NHW. No analysis was conducted for "Asian" or "Other." Limitations include moderate/substantial heterogeneity and reliance on electronic medical record data. CONCLUSION: Racial and ethnic disparities exist in the use of diabetes technologies. Its recognition is essential to advance solutions that promote equitable care in diabetes.
3. Comparative Effectiveness of Glucagon-like Peptide-1 Receptor Agonists Versus Oral Agents for Insulin Discontinuation in Type 2 Diabetes : A Target Trial Emulation.
In a large target trial emulation using US Veterans EHRs, initiating a GLP-1RA in basal insulin–treated T2D did not increase the likelihood of insulin discontinuation over 3 years compared with starting an SGLT2i or DPP-4i.
Impact: Provides high-quality, real-world comparative effectiveness data with a practice-informing negative result about insulin de-intensification expectations when adding GLP-1RAs.
Clinical Implications: Clinicians should not expect higher insulin discontinuation when adding GLP-1RAs to basal insulin compared with SGLT2i or DPP-4i; drug choice should prioritize cardio-renal benefits, weight, and patient-centered outcomes.
Key Findings
- Target trial emulation across 8,869 matched initiator sets found no increase in insulin discontinuation with GLP-1RA vs SGLT2i or DPP-4i over 3 years.
- Insulin discontinuation was defined pragmatically as a ≥12-month prescription gap, enhancing clinical interpretability.
- Cohort largely older male veterans; most GLP-1RA users received semaglutide; most SGLT2i users empagliflozin.
Methodological Strengths
- Explicit target trial emulation with active-comparator new-user design in a national EHR.
- Large sample with matched initiator sets across three therapeutic classes.
Limitations
- Residual confounding and exposure/outcome misclassification inherent to EHR-based studies.
- Generalizability limited by older, predominantly male veteran population.
Future Directions: Prospective pragmatic trials and mechanistic studies to identify predictors of successful insulin de-intensification across drug classes.
BACKGROUND: Addition of glucagon-like peptide-1 receptor agonists (GLP-1RAs) to basal insulin can decrease insulin requirements, but whether it permits insulin discontinuation is unclear. OBJECTIVE: To compare rates of insulin discontinuation among patients with type 2 diabetes (T2D) receiving basal insulin who initiated treatment with a GLP-1RA, sodium-glucose cotransporter-2 inhibitor (SGLT-2i), or dipeptidyl peptidase-4 inhibitor (DPP-4i) between 2020 and 2022. DESIGN: Target trial emulation. SETTING: U.S. Veterans Health Administration electronic health record (EHR) data. PARTICIPANTS: Veterans with T2D receiving basal insulin. MEASUREMENTS: Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up. RESULTS: Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A LIMITATION: Possible residual confounding; misclassification of exposure and outcome using EHRs may bias associations toward the null. CONCLUSION: Among veterans with T2D receiving basal insulin therapy, addition of GLP-1RA did not increase the chances of stopping insulin therapy compared with SGLT-2i or DPP-4i therapy. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.