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.
BACKGROUND: Oral semaglutide at a dose of 25 mg may provide an alternative treatment option to injectable semaglutide (2.4 mg) and higher-dose oral semaglutide (50 mg) for persons with overweight or obesity. METHODS: In a 71-week, double-blind, randomized, placebo-controlled trial conducted at 22 sites in four countries, we enrolled persons without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication. The participants were randomly assigned in a 2:1 ratio to receive oral semaglutide (25 mg) or placebo once daily, plus lifestyle interventions. The coprimary end points at week 64 were the percent change in body weight and a reduction of 5% or more in body weight; confirmatory secondary end points included reductions in body weight of 10% or more, 15% or more, and 20% or more and the change in the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score. RESULTS: A total of 205 participants were randomly assigned to receive oral semaglutide, and 102 to receive placebo. The estimated mean change in body weight from baseline to week 64 was -13.6% in the oral semaglutide group and -2.2% in the placebo group (estimated difference, -11.4 percentage points; 95% confidence interval, -13.9 to -9.0; P<0.001). Participants in the oral semaglutide group were significantly more likely than those in the placebo group to have body-weight reductions of 5% or more, 10% or more, 15% or more, and 20% or more (P<0.001 for all comparisons) and to have an improved IWQOL-Lite-CT Physical Function score (P<0.001). Gastrointestinal adverse events were more common with oral semaglutide than with placebo (74.0% vs. 42.2%). CONCLUSIONS: Oral semaglutide at a dose of 25 mg once daily resulted in a greater mean reduction in body weight than placebo in participants with overweight or obesity. (Funded by Novo Nordisk; OASIS 4 ClinicalTrials.gov number, NCT05564117.).
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.
BACKGROUND: Limitations still exist in the surgical strategies for primary aldosteronism (PA), the most common cause of secondary hypertension. This study aimed to compare the effectiveness of 68Ga-pentixafor PET/CT versus adrenal venous sampling (AVS) in guiding surgical management for PA. MATERIALS AND METHODS: A prospective cohort of 197 PA patients were assigned to Group PET (n = 137) and Group AVS (n = 60), in which the surgical interventions were guided by 68Ga-pentixafor PET/CT and AVS, respectively. Postoperative clinical and biochemical outcomes were analyzed referring to Primary Aldosteronism Surgical Outcomes classification system, with subgroup analysis on clinical characteristics and outcomes conducted in Group PET. RESULTS: During a median follow-up of 27 (16, 39) months, the postoperative clinical and biochemical outcomes were comparable between 134 patients in Group PET and 57 patients in Group AVS, with unilateral or bilateral adrenal lesions. The rates of complete, partial, and absent clinical success were 51.5%, 38.1%, 10.4% in Group PET, and 35.1%, 50.9%, 14.0% in Group AVS (P = 0.115). For biochemical success, the corresponding rates were 82.1%, 12.7%, 5.2% in Group PET, and 75.4%, 17.5%, 7.0% in Group AVS (P = 0.533). The proportion of complete biochemical success was significantly higher than that of complete clinical success (80.10% vs 46.6%, P<0.001). Female gender was associated with increased likelihood of complete clinical and biochemical success, and lower preoperative systolic blood pressure and shorter duration of hypertension indicated increased likelihood of complete clinical success. The SUVmax was significantly correlated with lesion diameters, age, duration of hypertension, blood potassium level, pathological type and clinical outcomes. A cutoff value of 5.5 for SUVmax demonstrated a sensitivity of 82.8% and a specificity of 92.6% in identifying functional adrenal lesions with autonomous aldosterone secretion. CONCLUSIONS: 68Ga-pentixafor PET/CT demonstrated potential non-inferiority to AVS in guiding the surgical management for PA patients, with comparable postoperative clinical and biochemical outcomes.
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.
Existing evaluations of the National Health Service Diabetes Prevention Programme (NHS DPP) in England have demonstrated associated reductions in body weight, hemoglobin A1c and incident type 2 diabetes (T2D). In this study, we examined associations between completion of the NHS DPP and incidence of T2D and 30 other long-term conditions (LTCs), including LTCs considered linked to the program's interventional goals of body weight reduction, increased physical activity and improved diet quality (LTC-L) and LTCs considered to be possibly linked to those goals (LTC-PL). We found that completers of the NHS DPP had lower incidences of T2D, LTC-L and LTC-PL compared to non-attenders. Although these associations attenuated over time, they remained significant for all outcomes at 24 months with an odds ratio of 0.53 (95% confidence interval: 0.48-0.59) for T2D and rate ratios of 0.79 (0.74-0.84) and 0.80 (0.74-0.88) for LTC-L and LTC-PL, respectively. However, we were not able to directly conclude whether lower incidence rates were a direct result of completing the NHS DPP or due to residual bias stemming from unmeasured confounding and imprecision in the estimation of diagnosis.