Daily Endocrinology Research Analysis
Analyzed 30 papers and selected 3 impactful papers.
Summary
Analyzed 30 papers and selected 3 impactful articles.
Selected Articles
1. Effect of GLP-1 receptor agonists at doses for obesity management on muscle health: systematic review and meta-analysis of randomized controlled trials (RCTs).
Across 7 RCTs (n=821), GLP-1RAs at obesity doses increased lean mass as a proportion of total weight (+1.81%) but decreased absolute lean mass (−1.74 kg), with semaglutide showing the largest absolute loss (−5.44 kg). Heterogeneity was low for proportional change but high for absolute changes, supporting combined pharmacotherapy with resistance exercise and adequate protein to preserve muscle.
Impact: Clarifies a critical safety/efficacy concern for widespread GLP-1RA use in obesity by disentangling proportional vs absolute lean mass effects, guiding comprehensive care plans.
Clinical Implications: Do not avoid GLP-1RAs solely due to fear of sarcopenia; instead pair with resistance training and adequate protein, monitor lean mass (e.g., DXA/BIA), and consider higher-risk patients (older adults, frailty) for targeted exercise/nutrition support.
Key Findings
- Lean mass proportion increased by +1.81% (95% CI 1.10–2.52; I²=7%).
- Absolute lean mass decreased by −1.74 kg (95% CI −3.04 to −0.45; I²=98%).
- Semaglutide showed the largest absolute lean mass reduction (−5.44 kg; 95% CI −7.07 to −3.81).
Methodological Strengths
- Random-effects meta-analysis of RCTs with pre-specified outcomes on lean mass (absolute, relative, and proportion).
- Low heterogeneity for proportional change and consistent directionality across trials.
Limitations
- High heterogeneity (I²=98%) for absolute and percentage lean mass changes limits precision.
- Variable trial durations and measurement modalities; limited functional outcomes (strength/performance) reporting.
Future Directions: Integrate standardized body composition and muscle function endpoints (e.g., handgrip, chair rise) into obesity RCTs; test exercise-protein adjuncts prospectively with GLP-1RAs to mitigate lean mass loss.
INTRODUCTION: The impact of GLP-1 receptor agonists (GLP1-RA) treatment on lean mass and body composition in patients with obesity is not fully understood. METHODOLOGY: Systematic review and meta-analysis of RCTs including patients with obesity treated with GLP1-RA at obesity doses, compared with placebo. Search was conducted in PubMed, Embase, and LILACS in March 2025. A meta-analysis was performed using a random-effects model to evaluate the change in lean mass as a proportion of total weight, the absolute and relative changes in lean mass, and adverse effects. RESULTS: Seven studies (821 patients) were included in the analysis. GLP1-RA significantly improved lean mass as a proportion of total weight, with an observed increase of 1.81% (95% CI: 1.1- 2.52; p < 0.00001; I² = 7%). However, a significant decrease was observed in the absolute change in lean mass (-1.74 kg; 95% CI: -3.04 to -0.45; p < 0.00001; I² = 98%) and in the percentage of lean mass (-3.06%; 95% CI: -5.10 to -1.02; p < 0.00001; I² = 98%). Semaglutide demonstrated the most significant reduction in absolute lean mass, with a loss of -5.44 kg (95% CI: -7.07 to -3.81; p < 0.00001). CONCLUSIONS: There is an improvement in body composition due to an increase in lean mass as a proportion of total weight, an effect that could be amplified with the use of semaglutide. Our results suggest that lean mass loss should not be considered a limitation for the use of these drugs in patients with obesity. However, it is essential to accompany drug treatment with nutritional and physical exercise interventions to preserve or improve muscle mass and optimize clinical outcomes.
2. Associations of testosterone, sex hormone-binding globulin, and related hormones with risks of cancer death, incident cancer, and incident prostate cancer in men: individual participant data meta-analyses.
In pooled IPD from large prospective cohorts, lower total testosterone and dihydrotestosterone were associated with higher cancer mortality, with risk increasing below ~8.6 nmol/L. Lower SHBG or luteinising hormone predicted higher incident prostate cancer, while testosterone itself did not. Findings position sex hormones as candidate biomarkers to refine cancer risk stratification in men.
Impact: Provides high-quality, adjusted IPD evidence linking androgen and binding protein levels to cancer outcomes, informing risk assessment beyond traditional factors.
Clinical Implications: Consider measuring testosterone, SHBG, and LH in men at elevated oncologic risk to refine counseling; extremely low testosterone may flag higher all-cancer mortality risk, while low SHBG/LH suggests higher prostate cancer risk—without implying causality or mandating hormone normalization.
Key Findings
- Lower total testosterone (Q1 vs Q5) associated with higher cancer death (HR 1.18; 95% CI 1.04–1.34); similar for dihydrotestosterone (HR 1.21; 95% CI 1.06–1.38).
- Cancer death risk increased at testosterone <8.6 nmol/L; incident cancer risk rose <7.3 nmol/L.
- Lower SHBG or LH associated with higher incident prostate cancer (SHBG Q1:Q5 HR 1.28; LH Q1:Q5 HR 1.45); testosterone not associated.
Methodological Strengths
- IPD meta-analysis with standardized adjustments across cohorts and mass spectrometry hormone assays.
- Prospective registration (PROSPERO) and formal risk-of-bias assessment.
Limitations
- Observational cohorts cannot establish causality; residual confounding is possible.
- Hormone measurements from single timepoints may not capture longitudinal variability.
Future Directions: Test whether integrating sex hormones with genetic and clinical predictors improves cancer risk models; evaluate longitudinal hormone trajectories and intervention implications.
BACKGROUND: Whether differences in sex hormones influence cancer risk in men remains uncertain. We aimed to clarify the association of circulating testosterone, sex hormone-binding globulin (SHBG), and related hormones with risks of cancer death, incident cancer, and incident prostate cancer by means of individual participant data (IPD) meta-analyses. METHODS: A systematic review of the literature using MEDLINE, Embase, OpenGrey, and Mednar was conducted from date of database inception till July 22, 2019, with bridge searches using MEDLINE till Jan 21, 2026. Prospective cohort studies comprising 1000 or more community-dwelling men with testosterone concentrations measured using mass spectrometry and a follow-up of 5 years or more were included. Two-stage random-effects meta-analyses were performed, controlling for baseline age, previous cancer, BMI, marital status, alcohol consumption, smoking status, physical activity, hypertension status, and diabetes status. Risk of bias was assessed using the Newcastle-Ottawa method. This study was prospectively registered with PROSPERO (CRD42019139668). FINDINGS: Ten studies provided IPD (24 510 men; 276 931 participant-years; 2847 cancer deaths), and one provided aggregate data (1535 men; 184 cancer deaths). Five studies provided IPD for incident prostate cancer (12 280 men; 151 373 participant-years; 918 events). Lower total testosterone concentrations were associated with higher risk of cancer death (median of first vs median of fifth quintile [Q1:Q5] hazard ratio [HR] 1·18, 95% CI 1·04-1·34), as were lower dihydrotestosterone concentrations (Q1:Q5 1·21, 1·06-1·38), the risk increasing with testosterone concentrations less than 8.6 nmol/L. SHBG and luteinising hormone concentrations were non-linearly associated with risk of cancer death (lowest risk: SHBG Q3:Q5 HR 0·81, 95% CI 0·68-0·97; luteinising hormone Q2:Q5 0·73, 0·59-0·90). Men with very low baseline testosterone concentrations had a higher risk of incident cancer, the risk increasing with concentrations less than 7.3 nmol/L. Lower SHBG or lower luteinising hormone concentrations were associated with higher risk of incident prostate cancer (Q1:Q5 HR 1·28, 95% CI 1·07-1·54; Q1:Q5 1·45, 1·13-1·86); testosterone was not associated with this outcome. Estimates of I INTERPRETATION: Lower total testosterone or dihydrotestosterone concentrations in men were associated with a higher risk of cancer death, and mid-range SHBG or luteinising hormone concentrations were associated with a lower risk. Men with lower SHBG or luteinising hormone concentrations had an associated higher risk of incident prostate cancer. Sex hormones could serve as biomarkers for cancer risk, warranting further investigation of these observed associations. FUNDING: Medical Research Future Fund; Government of Western Australia; Lawley Pharmaceuticals.
3. Efficacy of Initiation of Semaglutide versus SGLT2 inhibitors in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Multicenter Propensity-Matched Real-World Study.
In >110,000 propensity-matched MASLD patients, semaglutide initiation was associated with lower risks of all-cause mortality, hospitalization, MACE, and major adverse liver outcomes versus SGLT2 inhibitors at 1 and 5 years, with kidney benefits emerging by 5 years.
Impact: Largest real-world head-to-head comparison in MASLD to date, informing drug selection where RCTs are lacking.
Clinical Implications: For MASLD with metabolic comorbidity, semaglutide may be preferred when aiming to reduce mortality and major liver/cardiometabolic events, pending confirmation in randomized trials; monitor for class-specific adverse effects and consider individual cardiometabolic priorities.
Key Findings
- At 1 year: HRs vs SGLT2i were 0.382 for mortality, 0.444 for hospitalization, 0.502 for MACE, 0.361 for MALO.
- At 5 years: HRs remained favorable (mortality 0.494; hospitalization 0.565; MACE 0.584; MALO 0.494).
- MAKE showed no difference at 1 year (HR 0.998) but improved at 5 years (HR 0.858).
Methodological Strengths
- Large multicenter network with >50-covariate propensity score matching and balanced cohorts.
- Time-to-event analyses over 1 and 5 years across multiple clinically meaningful endpoints.
Limitations
- Retrospective observational design with risk of residual confounding and confounding by indication.
- Outcome ascertainment relies on EHR coding; medication dose/adherence details may be limited.
Future Directions: Head-to-head randomized trials in MASLD comparing GLP-1RAs and SGLT2is with histologic endpoints; mechanistic studies on liver, cardiovascular, and renal pathways mediating differential benefits.
OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common and linked to cardiometabolic comorbidities, with few direct comparisons between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is). METHODS: This multicenter, retrospective, propensity score-matched cohort study utilized data from the TriNetX U.S. Collaborative Network. Adults with MASLD and at least one metabolic comorbidity were identified as new initiators of semaglutide (n=128,332) or SGLT2is (n=100,542), excluding alternative exposures and confounding liver etiologies. One-to-one propensity score matching on >50 covariates yielded balanced cohorts of 55,525 patients each. Time-to-event outcomes, including all-cause mortality, hospitalization, major adverse cardiovascular events (MACE), major adverse liver outcomes (MALO), major adverse kidney events (MAKE), ascites, hepatic failure, and hepatic encephalopathy, were evaluated at 1-year and 5-year follow-ups using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: Semaglutide was linked to significant risk reductions compared to SGLT2is. At 1-year, hazard ratios (HRs) were 0.382 (95% CI 0.338-0.430) for all-cause mortality, 0.444 (95% CI 0.429-0.459) for all-cause hospitalization, 0.502 (95% CI 0.476-0.530) for MACE, and 0.361 (95% CI 0.316-0.412) for MALO. At 5-years, the corresponding HRs were 0.494 (95% CI 0.459-0.531), 0.565 (95% CI 0.551-0.579), 0.584 (95% CI 0.560-0.609), and 0.494 (95% CI 0.452-0.540). MAKE showed no difference at 1-year (HR 0.998), but a reduction at 5-years (HR 0.858; 95% CI 0.789-0.933). Individual liver events (ascites, hepatic failure) followed similar patterns. CONCLUSIONS: In this large real-world MASLD cohort, initiating semaglutide was linked to potential reductions in mortality, hospitalization, and adverse cardiometabolic, liver, and kidney outcomes compared to SGLT2is.