Daily Endocrinology Research Analysis
Today’s top endocrinology papers span treatment, diagnosis, and prevention: a NEJM randomized trial shows substantial weight loss with once‑daily oral semaglutide 25 mg; a prospective cohort suggests 68Ga‑pentixafor PET/CT can guide surgery in primary aldosteronism comparably to adrenal venous sampling; and a Nature Medicine real‑world analysis links completion of the NHS Diabetes Prevention Programme to lower incidence of type 2 diabetes and other long‑term conditions.
Summary
Today’s top endocrinology papers span treatment, diagnosis, and prevention: a NEJM randomized trial shows substantial weight loss with once‑daily oral semaglutide 25 mg; a prospective cohort suggests 68Ga‑pentixafor PET/CT can guide surgery in primary aldosteronism comparably to adrenal venous sampling; and a Nature Medicine real‑world analysis links completion of the NHS Diabetes Prevention Programme to lower incidence of type 2 diabetes and other long‑term conditions.
Research Themes
- Obesity pharmacotherapy and GLP-1 receptor agonists
- Noninvasive imaging to guide endocrine surgery
- Lifestyle-based diabetes prevention and multimorbidity
Selected Articles
1. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity.
In adults with overweight/obesity without diabetes, once-daily oral semaglutide 25 mg produced 11.4 percentage points greater weight loss vs placebo at week 64 and higher odds of achieving ≥5–20% weight loss, with more gastrointestinal adverse events.
Impact: Provides high-quality RCT evidence supporting an oral GLP-1 RA option that approaches injectable efficacy while expanding patient choice and access.
Clinical Implications: Oral semaglutide 25 mg can be considered for chronic weight management in adults without diabetes, balancing efficacy with gastrointestinal tolerability and patient preference for oral therapy.
Key Findings
- Mean weight change at week 64: −13.6% (semaglutide) vs −2.2% (placebo); difference −11.4 percentage points (95% CI, −13.9 to −9.0; P<0.001).
- Higher proportions achieved ≥5%, ≥10%, ≥15%, and ≥20% weight loss with semaglutide (all P<0.001).
- GI adverse events were more frequent with semaglutide (74.0%) vs placebo (42.2%).
Methodological Strengths
- Double-blind, randomized, placebo-controlled, multicenter design with prespecified coprimary endpoints.
- Long treatment duration (71 weeks) with comprehensive efficacy and patient-reported outcomes.
Limitations
- Industry-funded trial without active comparator against injectable semaglutide 2.4 mg or higher-dose oral formulations.
- Population excluded people with diabetes; generalizability and long-term safety beyond 71 weeks remain to be defined.
Future Directions: Head-to-head comparisons versus injectable semaglutide and dose–response studies across oral doses; longer-term safety and maintenance of weight loss; evaluation in people with diabetes and cardiometabolic outcomes.
2. 68Ga-pentixafor PET/CT versus adrenal venous sampling in guiding surgical management for primary aldosteronism: a prospective cohort study on postoperative outcomes.
In a prospective cohort of 197 patients with primary aldosteronism, surgical guidance using 68Ga-pentixafor PET/CT yielded postoperative clinical and biochemical outcomes comparable to AVS. SUVmax ≥5.5 identified functional aldosterone‑producing lesions with high sensitivity and specificity.
Impact: Suggests a noninvasive imaging alternative to AVS for lateralization and surgical decision-making in PA, potentially improving access and reducing procedural risks.
Clinical Implications: 68Ga-pentixafor PET/CT may be used to guide surgery in PA where AVS is unavailable, contraindicated, or inconclusive, with attention to lesion SUVmax and clinical context.
Key Findings
- Clinical success (complete/partial/absent): PET 51.5%/38.1%/10.4% vs AVS 35.1%/50.9%/14.0% (P=0.115).
- Biochemical success (complete/partial/absent): PET 82.1%/12.7%/5.2% vs AVS 75.4%/17.5%/7.0% (P=0.533).
- SUVmax cutoff 5.5 identified functional aldosterone lesions (sensitivity 82.8%, specificity 92.6%).
Methodological Strengths
- Prospective cohort with predefined surgical outcome classification (PASO).
- Median follow-up of 27 months enabling assessment of sustained outcomes.
Limitations
- Nonrandomized design with potential selection bias between imaging- and AVS-guided groups.
- Single imaging modality and center-specific protocols may limit generalizability.
Future Directions: Randomized trials comparing PET/CT-guided versus AVS-guided surgery; cost-effectiveness analyses; external validation of SUVmax thresholds and integration with genetic/histopathologic subtypes.
3. Association between the English National Health Service Diabetes Prevention Programme and incident multiple long-term conditions.
Completion of the NHS Diabetes Prevention Programme was associated with lower 24‑month incidence of type 2 diabetes (OR 0.53) and reduced rates of multiple long-term conditions plausibly linked to weight, activity, and diet, though residual confounding cannot be excluded.
Impact: Provides large-scale real-world evidence that structured lifestyle prevention may reduce multimorbidity alongside diabetes incidence, informing population-level policy.
Clinical Implications: Health systems can prioritize completion and engagement in diabetes prevention programs to potentially reduce T2D and broader long-term condition burden, while recognizing observational limitations.
Key Findings
- Program completion associated with lower 24-month T2D incidence (OR 0.53, 95% CI 0.48–0.59).
- Lower rates of LTCs linked to program goals: LTC-L rate ratio 0.79 (0.74–0.84) and LTC-PL 0.80 (0.74–0.88).
- Associations attenuated over time and may be influenced by residual confounding and diagnostic imprecision.
Methodological Strengths
- Large-scale real-world dataset linking program completion with clinical outcomes across multiple conditions.
- Use of distinct LTC groupings aligned to hypothesized intervention pathways (weight, activity, diet).
Limitations
- Observational design with risk of unmeasured confounding and selection bias among completers vs non-attenders.
- Attenuation of associations over time and potential misclassification of diagnoses.
Future Directions: Quasi-experimental designs (e.g., instrumental variables, regression discontinuity) to strengthen causal inference; evaluation of strategies to improve program completion; long-term morbidity and mortality endpoints.