This Week in Endocrinology — Aug 25, 2026

Welcome to This Week in Endocrinology. This week we're covering 10 notable papers spanning obesity pharmacotherapy and the new dual-agonist era, diabetes therapeutics from novel oral agents to immunotherapy, and a cluster of thyroid, adrenal and rare-disease papers with immediate implications for how we monitor patients. Let's dive in.

We start with obesity, where guidance and pharmacology are both moving. Annals of Internal Medicine published a synopsis of the updated 2025 Veterans Affairs and Department of Defense clinical practice guideline on adult overweight and obesity, from Corrado and colleagues [1]. Built on a systematic review through January of this year and graded using standard methods, the guideline frames obesity explicitly as a chronic relapsing neurohormonal disease. Screening is suggested for all adults at a body mass index of 25 or above, and 23 or above for Asian adults, with waist circumference and clinical context used to refine risk. Comprehensive lifestyle intervention remains the strongly recommended foundation, but the practical shift for clinicians is this: the panel found insufficient evidence to support delaying drug therapy until lifestyle intervention has been tried and completed. There is no requirement to finish a lifestyle programme before starting pharmacotherapy, and the guideline explicitly discourages stopping an effective medication, given the predictable regain that follows. New recommendations cover GLP-1 receptor agonist–containing medicines, endoscopic therapies and metabolic and bariatric surgery, all within a stigma-informed, longitudinal model of care.

Against that backdrop, two papers examine what comes after the GLP-1 and GLP-1–GIP agents. In The Lancet Diabetes and Endocrinology, Hsia and colleagues report a phase 2, placebo-controlled trial of mazdutide, a dual glucagon and GLP-1 receptor agonist, in 179 adults with obesity or overweight without type 2 diabetes across 24 United States centres [3]. At 32 weeks, weight fell by roughly 16 percent on the 10 milligram dose and about 18 percent on 16 milligrams, compared with essentially no change on placebo, and further reduction continued out to 48 weeks. The lower maintenance strategy, 3 escalating to 6 milligrams, delivered a more modest seven percent or so. Adverse events were predominantly gastrointestinal and mostly mild to moderate, but one in five participants on the top dose discontinued because of them, which is a meaningful tolerability signal for a drug whose glucagon arm is meant to add energy expenditure. Complementing that single trial, Diabetes Care published a meta-analysis from Roessler and colleagues pooling 16 randomised trials and more than six thousand participants treated with dual GLP-1 and glucagon receptor agonists [4]. Placebo-corrected weight loss averaged about seven percent, with consistent improvement across waist circumference, atherogenic lipids, HbA1c and haemodynamic measures. The more interesting comparison is head to head against selective GLP-1 agonists, where the dual agents produced a greater reduction in triglycerides but no clear separation on the other outcomes. So the honest reading is that glucagon co-agonism looks metabolically active, particularly on the liver-lipid axis, but has not yet demonstrated a decisive advantage over what we already prescribe. Large outcome trials will decide it.

Turning to diabetes therapeutics, Diabetes Care carried two papers pulling in different directions on durability. Ji and colleagues report a phase 3 randomised trial of HTD1801, an oral agent, as monotherapy in 407 participants with type 2 diabetes inadequately controlled on diet and exercise, with a baseline HbA1c of 8.5 percent [7]. At 24 weeks, HbA1c fell about 0.7 percentage points more with active treatment than with placebo, the effect held through 52 weeks, and cardiometabolic and inflammatory markers improved. The main tolerability issue was mild to moderate diarrhoea in about one in ten participants, mostly at initiation. That is a respectable oral monotherapy signal, though the comparator here is placebo, not metformin. The contrast comes from So and colleagues, who followed the BANDIT trial participants for a year after stopping oral baricitinib in recent-onset type 1 diabetes [8]. Baricitinib had preserved beta-cell function during 48 weeks of treatment. Twenty-four weeks after cessation, C-peptide was still significantly higher in the treated group, but by week 96 that difference had disappeared, and there were no differences in insulin dose, HbA1c or continuous glucose monitoring measures during follow-up. The immunological signature also reverted, with the treatment-associated changes in effector memory CD8 T cells resolving. One post hoc observation is worth holding onto: treated adults appeared to maintain beta-cell function after stopping, whereas treated children lost C-peptide. The conclusion is plain — benefit from this oral immunotherapy wanes off drug, and durable protection is likely to require continuous treatment.

On the thyroid front, two papers address very different problems. In the Journal of Clinical Endocrinology and Metabolism, Yamauchi and colleagues report the first Japanese real-world magnetic resonance imaging study of teprotumumab for thyroid eye disease, covering all 18 patients treated at a single university hospital, with a historical comparison cohort of 20 patients given intravenous glucocorticoids [5]. Over 24 weeks, proptosis improved by about three millimetres, clinical activity score fell from four points to one, diplopia improved in 9 of the 15 affected patients, and thyroid-stimulating antibody titres dropped substantially. The imaging finding is the novel part: teprotumumab shrank both extraocular muscle and orbital fat, whereas intravenous glucocorticoids reduced muscle area but actually increased orbital fat. Inflamed muscles identified on imaging responded to both therapies. That gives a mechanistic rationale for preferring the antibody where fat expansion is driving proptosis. Then in Thyroid, Yamin and colleagues report a nationwide cohort of 521 pregnancies following preconception hemithyroidectomy in euthyroid women, matched to more than four thousand controls with intact glands [10]. Overt gestational hypothyroidism occurred in roughly one in five of the hemithyroidectomy pregnancies versus about two percent of controls, thyroid hormone replacement was needed in about one in five compared with under three percent, and TSH above 10 was almost exclusive to the surgical group. Risk was highest after surgery for thyroid cancer, and two thirds of the affected women already met biochemical criteria at their very first prenatal visit — meaning the deficiency predated conception. Reassuringly, absolute rates of adverse obstetric outcomes did not differ between the groups. The uncomfortable finding is the surveillance gap: close to thirty percent of women with a prior hemilobectomy had no first-trimester TSH check at all.

Finally, three papers on less common endocrine disease. Endocrine Reviews published a review from Merke and Auchus on the changing treatment landscape in congenital adrenal hyperplasia [2]. The argument is that conventional supraphysiological, non-physiologically timed glucocorticoid dosing buys disease control at the cost of long-term comorbidity, and that circadian delivery — modified-release hydrocortisone or continuous subcutaneous infusion — achieves better control at the same or lower daily dose. Beyond that, the corticotropin-releasing factor type 1 receptor antagonist crinecerfont enables a genuine block-and-replace approach with near-physiological glucocorticoid dosing, with the melanocortin type 2 receptor antagonist atumelnant and the anti-ACTH antibody asedebart in trials. Nature Reviews Endocrinology published international Delphi consensus recommendations on diagnosing hypochondroplasia, from Dauber and colleagues, integrating clinical, anthropometric, radiographic, neuroimaging and genetic criteria into major and minor diagnostic criteria with guidance on when to use molecular testing [6] — useful for anyone seeing disproportionate short stature with relative macrocephaly in early childhood, where diagnosis is often delayed. And in the Journal of Clinical Endocrinology and Metabolism, Elshafie and colleagues describe 27 consecutive patients with catecholamine-secreting phaeochromocytoma and paraganglioma treated with octreotide at two referral centres in Oman [9]. Median plasma noradrenaline fell by roughly two thirds, blood pressure fell by around thirty systolic points, and among the eleven patients with diabetes, HbA1c dropped from about 8.6 to 6.2 percent. Seventeen went on to surgery. This is a small retrospective series without a control group, so it is hypothesis-generating rather than practice-defining, but it supports octreotide as an adjunct in patients who are difficult to stabilise before an operation.

If you only have time for one paper this week, make it the Thyroid nationwide study on pregnancy after hemithyroidectomy [10]. It quantifies a common, entirely preventable failure — a woman who left your clinic euthyroid on one lobe and reaches her first antenatal visit already overtly hypothyroid — and it identifies exactly where the system is leaking.

Here are the key takeaways from this week in Endocrinology. First, the updated Veterans Affairs and Department of Defense guideline removes the requirement to complete lifestyle intervention before starting obesity pharmacotherapy, and warns against stopping medications that are working. Second, dual glucagon and GLP-1 agonism produces substantial weight loss, with mazdutide reaching about eighteen percent at the top dose, but tolerability limits that dose and the pooled evidence shows only a triglyceride advantage over selective GLP-1 agents so far. Third, immunotherapy benefit in new-onset type 1 diabetes does not persist after the drug is stopped — plan for continuous treatment. Fourth, imaging suggests teprotumumab and intravenous glucocorticoids act differently on orbital fat, favouring the antibody in fat-predominant thyroid eye disease. And fifth, every woman with a prior hemithyroidectomy who is pregnant or planning pregnancy needs a TSH check at the first prenatal visit, and ideally before conception.

That's your roundup for This Week in Endocrinology. The full transcript and references are available on the episode page in your AudioScholar library. This is an AI-curated summary — for clinical decisions, always consult primary sources and current guidelines. See you next week.

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This is an automated summary generated by artificial intelligence, which can make mistakes. Always review the original source materials.