Daily Endocrinology Research Analysis
Three impactful studies shape current endocrinology practice: a global consensus harmonizes MASLD/MASH management in the resmetirom era; a nationwide cohort quantifies elevated gallbladder/biliary risk with incretin drugs vs SGLT2 inhibitors irrespective of BMI; and a large ACCORD analysis links visit-to-visit lipid variability to incident heart failure in type 2 diabetes. Together, they refine screening, drug safety, and cardiometabolic risk stratification.
Summary
Three impactful studies shape current endocrinology practice: a global consensus harmonizes MASLD/MASH management in the resmetirom era; a nationwide cohort quantifies elevated gallbladder/biliary risk with incretin drugs vs SGLT2 inhibitors irrespective of BMI; and a large ACCORD analysis links visit-to-visit lipid variability to incident heart failure in type 2 diabetes. Together, they refine screening, drug safety, and cardiometabolic risk stratification.
Research Themes
- Consensus-driven care for MASLD/MASH in metabolic endocrinology
- Drug safety of incretin therapies versus SGLT2 inhibitors
- Visit-to-visit lipid variability as a predictor of heart failure in T2D
Selected Articles
1. Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis.
This Delphi-based global consensus harmonizes MASLD/MASH care across 61 recent guidelines, delivering highly agreed statements (>90% agreement) and practical algorithms spanning screening, fibrosis assessment, and therapy in the era of resmetirom. It emphasizes mandatory screening in T2D, noninvasive fibrosis stratification (e.g., FIB-4, VCTE), and surveillance in advanced fibrosis.
Impact: Provides unified, timely guidance for a highly prevalent metabolic liver disease tightly linked to T2D, likely to standardize care and inform policy and payer decisions worldwide.
Clinical Implications: Adopt routine MASLD screening in T2D, apply FIB-4 and VCTE-based pathways for fibrosis risk, consider resmetirom for appropriate MASH phenotypes, and implement HCC surveillance in advanced fibrosis/cirrhosis. Multidisciplinary metabolic care and weight loss interventions remain foundational.
Key Findings
- Comprehensive synthesis of 61 guidelines produced consensus statements with >90% agreement via four-round Delphi.
- Mandatory MASLD screening and noninvasive fibrosis assessment recommended in high-risk populations, notably T2D.
- Guidance updated for the resmetirom era, with algorithms for diagnosis, risk stratification, and surveillance.
Methodological Strengths
- Systematic, multi-database search and structured appraisal across eight domains and 145 variables.
- Formal Delphi process with predefined supermajority threshold ensuring high-consensus statements.
Limitations
- Consensus relies on underlying heterogeneous guideline evidence quality.
- Guideline recommendations may require regional adaptation and future updates as new trials report.
Future Directions: Prospective validation of algorithms in diverse health systems, integration with T2D care pathways, and real-world effectiveness of resmetirom-inclusive strategies.
2. Incretin-based drugs and the risk of gallbladder or biliary tract diseases among patients with type 2 diabetes across categories of body mass index: a nationwide cohort study.
In a nationwide, active-comparator, new-user design with large propensity score–matched cohorts, both DPP4 inhibitors and GLP-1 receptor agonists were associated with higher gallbladder/biliary disease risk than SGLT2 inhibitors, without BMI-based effect modification. Findings are consistent across obese, overweight, and normal-weight categories.
Impact: Directly informs drug selection in T2D by quantifying biliary risks of widely used incretin agents versus SGLT2 inhibitors across BMI strata.
Clinical Implications: In patients at higher baseline risk for gallbladder/biliary diseases, preferential consideration of SGLT2 inhibitors over incretin agents may reduce biliary events. Counsel patients on biliary symptoms and monitor accordingly irrespective of BMI.
Key Findings
- DPP4 inhibitors vs SGLT2 inhibitors: HR 1.21 (95% CI 1.14–1.28) for gallbladder/biliary disease.
- GLP-1 receptor agonists vs SGLT2 inhibitors: HR 1.27 (95% CI 1.07–1.50).
- No evidence of BMI-based effect modification (p=0.83 and p=0.73 for interaction).
Methodological Strengths
- Active-comparator, new-user design with very large 1:1 propensity score–matched cohorts.
- Consistent results across BMI strata and across two independent comparator cohorts.
Limitations
- Observational claims data subject to residual confounding and potential misclassification.
- Absolute risks and follow-up durations are not detailed in the abstract.
Future Directions: Head-to-head pragmatic trials or high-quality emulations assessing absolute risks, duration-response, and mechanisms of biliary effects with incretin therapies.
3. Visit-to-Visit Variability in Lipid Levels and Risk of Incident Heart Failure in Adults With Type 2 Diabetes.
In ACCORD (n=9,443), higher visit-to-visit variability in TC, LDL-C, HDL-C, and TG independently predicted incident heart failure over 5 years, with adjusted HRs ranging 1.49–1.76 for highest vs lowest variability quartiles. Associations were consistent across variability metrics.
Impact: Highlights lipid variability as a modifiable risk dimension beyond mean levels for HF prevention in T2D, potentially informing targets for medication adherence and therapeutic smoothing.
Clinical Implications: Prioritize strategies that stabilize lipid levels (e.g., adherence optimization, long-acting statins/ezetimibe/PCSK9i), monitor variability in addition to means, and integrate HF risk stratification in T2D with lipid variability metrics.
Key Findings
- Across 9,443 T2D participants, 345 incident HF events occurred over 5.0 years.
- Highest quartile of lipid variability associated with higher HF risk: TC CV aHR 1.68; LDL-C CV aHR 1.76; HDL-C CV aHR 1.53; TG CV aHR 1.49.
- Findings were consistent using multiple variability metrics (CV, SD, variability independent of the mean).
Methodological Strengths
- Prospective repeated lipid measures at six time points enabling robust variability assessment.
- Adjusted Cox models in a large, well-characterized ACCORD cohort.
Limitations
- Observational analysis within a trial cohort; causality cannot be established.
- Generalizability may be limited to ACCORD-like populations.
Future Directions: Interventions targeting lipid variability (e.g., adherence programs, pharmacologic smoothing) should be tested for HF prevention in T2D.