Daily Endocrinology Research Analysis
Analyzed 78 papers and selected 3 impactful papers.
Summary
Top findings today span clinical trials, mechanistic human physiology, and global practice guidelines. Weekly semaglutide reduced all-cause hospitalizations in high-risk patients without diabetes (SELECT), a human tracer study challenges presumed hepatic glucagon resistance in steatosis, and the International Menopause Society issued GRADE-based recommendations that may reshape midlife women’s health care.
Research Themes
- Cardiometabolic therapeutics reduce healthcare utilization
- Revisiting liver–alpha cell axis in metabolic disease
- Evidence-based menopause care using GRADE/AGREE II
Selected Articles
1. Semaglutide and Hospitalizations in Patients With Obesity and Established Cardiovascular Disease: An Exploratory Analysis of the SELECT Randomized Clinical Trial.
In 17,604 adults with established CVD and overweight/obesity without diabetes, once-weekly semaglutide 2.4 mg reduced total hospitalizations (mean ratio 0.90, 95% CI 0.85-0.95) and days hospitalized (rate ratio 0.89) versus placebo over a median 41.8 months. Reductions were consistent for serious adverse event admissions and across prespecified subgroups.
Impact: Extends the benefits of GLP-1 receptor agonist therapy beyond CV event reduction to tangible health system outcomes (hospitalizations) in a large global RCT.
Clinical Implications: For adults with obesity and established CVD (without diabetes), semaglutide 2.4 mg weekly can be considered to reduce hospitalizations and inpatient days, informing value-based care and payer decisions.
Key Findings
- Total hospitalizations were lower with semaglutide vs placebo: 18.3 vs 20.4 per 100 patient-years (mean ratio 0.90; 95% CI 0.85-0.95; P<.001).
- Days hospitalized for any indication were reduced: 157.2 vs 176.2 per 100 patient-years (rate ratio 0.89; 95% CI 0.82-0.98; P=.01).
- Hospitalizations for serious adverse events were also reduced (mean ratio 0.89; 95% CI 0.84-0.94; P<.001).
- No heterogeneity of effect across BMI, age, or sex subgroups.
Methodological Strengths
- Prespecified exploratory analysis within a large, multicontinent randomized clinical trial.
- Robust sample size (n=17,604) with long median follow-up (41.8 months).
Limitations
- Exploratory nature of hospitalization endpoints with potential multiplicity concerns.
- Population included only patients without diabetes, which may limit generalizability.
Future Directions: Prospectively powered analyses and health economic evaluations to quantify cost savings and to assess applicability in broader cardiometabolic populations including diabetes.
IMPORTANCE: The primary analysis of the SELECT randomized clinical trial suggests that semaglutide reduced the rates of cardiovascular (CV) death, myocardial infarction, and stroke in patients with established CV disease (CVD) and overweight or obesity without diabetes. However, the effect of semaglutide on hospitalizations in this population remains unknown. OBJECTIVE: To determine the impact of semaglutide on total hospital admissions and duration of hospital stay. DESIGN, SETTING, AND PARTICIPANTS: The SELECT trial included patients aged 45 years or older with established CVD and a body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 27 or higher without diabetes at 804 clinical settings across North America, South America, Europe, Asia, Africa, and Australia. Patients were randomized from October 2018 to March 2021. This prespecified exploratory analysis was conducted from February 2024 to September 2025. INTERVENTIONS: Once-weekly subcutaneous semaglutide, 2.4 mg, or placebo.
2. International Menopause Society (IMS) recommendations and key messages on women's midlife health and menopause.
This guideline synthesizes evidence using GRADE/AGREE II to deliver 341 recommendations and 38 key messages across lifestyle, vasomotor and genitourinary symptoms, osteoporosis, cardiometabolic health, dementia, premature ovarian insufficiency, malignancy risks, and a new section on sarcopenia. It emphasizes individualized MHT and global adaptability considering regional variations.
Impact: A comprehensive, methods-transparent, international guideline likely to influence clinical care for millions of midlife women.
Clinical Implications: Provides a blueprint to standardize menopause care, refine MHT indications, incorporate sarcopenia assessment, and guide shared decision-making across diverse health systems.
Key Findings
- Developed 341 recommendations (285 evidence-based, 56 good practice points) and 38 key messages across 30 sections.
- Applied GRADE and AGREE II frameworks with global stakeholder input and Publication Steering Committee oversight.
- Introduced a new section addressing sarcopenia and discussed controversial topics such as media influence and ethics.
Methodological Strengths
- Rigorous evidence synthesis using GRADE and AGREE II.
- Broad, international, multi-stakeholder development process with predefined methodology.
Limitations
- Guideline impact depends on regional implementation and availability of therapies.
- Evidence heterogeneity across topics may limit strength of certain recommendations.
Future Directions: Prospective audits of implementation, living guideline updates as new evidence emerges, and evaluation of outcomes such as fracture reduction and cardiometabolic events.
Following a rigorous systematic review of the literature, the International Menopause Society (IMS) has produced detailed new recommendations and key messages on women's midlife health, menopause and menopause hormone therapy (MHT) to help guide healthcare professionals to optimize their management of women at this critical stage of life. The term MHT has been used to cover therapies including estrogens, progestogens and combined regimens. This guidance provides a summary of the recommendations and key messages generated from the systematic review process. The longer version, including the detailed text, key meta-analyses, references, figures and supplementary materials, will be published simultaneously online and can be accessed via the IMS website (https://www.imsociety.org/statements/ims-recommendations/). The quality of evidence and the strength of recommendations used in this guideline are based on the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) and the Appraisal of Guidelines for Research & Evaluation II (AGREE II) approaches. The new recommendations now include levels of evidence, grades of recommendations, good practice points and key messages. The recommendations were developed by a body of 38 authors and 26 support team members derived from the IMS and other organizations. Global stakeholder surveys, targeted at both healthcare providers and consumers, were initially conducted to identify the key questions. A Publication Steering Committee (PSC) provided oversight of the process through regular meetings and ensured consistency of methodology.
3. Hepatic steatosis in humans is associated with preserved glucagon action on amino acid metabolism.
Using hepatic vein catheterization with glucose and leucine tracers during a hyperglycemic clamp, the study found that hepatic steatosis did not impair glucagon-stimulated hepatic amino acid catabolism (leucine oxidation) or alter splanchnic amino acid balance responses. Thus, glucagon’s action on hepatic amino acid metabolism appears preserved in human steatosis.
Impact: Direct human mechanistic data challenge the widely cited hypothesis of hepatic glucagon resistance in steatosis, refining the liver–alpha cell axis concept.
Clinical Implications: Therapeutic strategies targeting glucagon signaling (e.g., receptor antagonists or multi-agonists) should consider preserved hepatic amino acid handling in steatosis; biomarker interpretation of hyperglucagonemia may need reappraisal.
Key Findings
- Hepatic leucine oxidation responses to stepwise glucagon infusion were not diminished by hepatic steatosis.
- Splanchnic balances of several amino acids differed among groups, but glucagon-induced changes were not modified by steatosis.
- Hepatic glucose metabolism responses to insulin and glucagon were not altered by the presence of steatosis.
- Trial registration: NCT05500586.
Methodological Strengths
- Direct hepatic vein catheterization with dual tracers enabling organ-specific flux quantification.
- Controlled hyperglycemic clamp with stepwise glucagon infusion allows causal inference on hormonal effects.
Limitations
- Sample size and group numbers are not specified in the abstract.
- Short-term physiological responses may not reflect chronic adaptations in advanced NASH or cirrhosis.
Future Directions: Extend to patients with advanced NASH and integrate amino acid fluxes with omics to delineate liver–pancreas feedback; test pharmacologic modulation of glucagon signaling.
BACKGROUND: Amino acid (AA) concentrations are increased in prediabetes and diabetes. Since AA stimulate glucagon secretion which should then increase hepatic AA catabolism, it has been hypothesized that hepatic resistance (associated with hepatic fat content) to glucagon's actions on AA metabolism leads to hyperglucagonemia and hyperglycemia. METHODS: To test this hypothesis, we therefore studied lean and obese individuals, the latter group with and without hepatic steatosis as defined by Proton Density Fat Fraction (PDFF) > 5%. After an overnight fast, femoral vein, femoral artery, and hepatic vein catheters were placed. [3-3H] glucose and L-[1-13C,15N]-leucine were used to measure glucose turnover and leucine oxidation respectively. During a hyperglycemic clamp, an amino acid mixture was infused together with insulin and glucagon (1.5 ng/kg/min 0 - 120 min; 3.0 ng/kg/min 120 - 240 min).