Endocrinology Update: Mazdutide OK, Mounjaro teens, CPAP benefit and More
From durable BRAF-directed responses and new Phase 2 efforts to real-world mortality data, pediatric breakthroughs, cost-saving growth therapies, international obesity launches, and an FDA call for more MDMA research—this update spans thyroid cancer, diabetes, hypoglycemia, PTSD, and rare endocrine disorders shaping modern endocrinology.
In Today’s Newsletter
🧪 ABP-745 Phase 2 first-patient-in (Atom Therapeutics) [1] [15 Sep 2025]
Context: Randomized, double-blind global study (>200 pts) across US/China/Australia vs placebo and colchicine (duration not stated).
Key point: Company enrolled the first patient in a multicountry Phase 2 trial for acute gout flares; Phase 1 showed acceptable safety/tolerability (endpoint not specified).
Implication: Signals pipeline investment and modality expansion.
🧠 FDA public CRL on MDMA-assisted therapy (Lykos) [2] [US • 15 Sep 2025]
https://www.hcplive.com/view/fda-releases-crl-detailing-safety-concerns-mdma-assisted-therapy-ptsd
Context: CRL details released 04 Sep 2025; earlier PDAC (Jun 2024) raised cardiovascular risk and unblinding concerns.
Key point: FDA cites lack of abuse-related AE capture, limited durability beyond 18 weeks, and selection bias (many prior MDMA users).
Implication: May influence prescriber choice and payer reviews pending full data.
🦋 Thyroid isthmus nodules: higher malignancy & risk alterations [3] [16 Sep 2025]
Context: Observational analyses (Afirma n=177,227 nodules; cancer cohorts) comparing isthmic vs lobar nodules/cancers.
Key point: Isthmic nodules ~2× Bethesda V–VI and higher rates of BRAF-like signatures and fusions vs lobar; calls for validation.
Implication: Could inform practice and payer discussions; interpretation depends on study design and confounding control.
📘 EASD’s first global guideline on diabetes distress [4] [19 Sep 2025]
Context: Guideline follows GRADE/RIGHT; co-developed with people living with T1D/T2D; assessment + management focus.
Key point: Recommends routine screening/monitoring with validated tools and evidence-based psycho-educational/psychological interventions.
Implication: May expand screening, initiation, and follow-up at scale.
🧒 Tirzepatide (Mounjaro) hits in SURPASS-PEDS (ages 10–17) [5] [18 Sep 2025]
https://www.fiercepharma.com/pharma/lillys-mounjaro-primed-expansion-kids-10-17-type-2-diabetes
Context: Phase 3, n=99; 30-week primary, 52-week extension; background metformin/insulin allowed.
Key point: A1C reduction vs placebo and BMI decreases (dose-dependent); safety aligned with incretin class; submissions to regulators noted.
Implication: May influence prescriber choice and payer reviews pending full data.
💸 Lonapegsomatropin (SKYTROFA) budget impact model (US) [6] [US • 19 Sep 2025]
Context: Hypothetical US payer budget impact model comparing market scenarios for pediatric GHD.
Key point: Inclusion of once-weekly lonapegsomatropin projected to reduce 5-year total plan costs vs daily/weekly GH mixes (assumptions per model).
Implication: Could inform practice and payer discussions; interpretation depends on study design and confounding control.
🇨🇳 Mazdutide (Innovent) gets NMPA nod for T2D glycemic control [7] [CN • 19 Sep 2025]
Context: First approved dual GCG/GLP-1 receptor agonist; approval supported by DREAMS-1/-2 Phase 3 (vs placebo/dulaglutide).
Key point: Superiority on HbA1c and weight with broader metabolic marker improvements; device convenience features noted.
Implication: Introduces competition that may affect pricing and formulary access.
🧫 Low-dose ATG (MELD-ATG) delays T1D progression [8] [EU • 19 Sep 2025]
Context: Adaptive, double-blind, placebo-controlled trial (ages 5–25) presented at EASD; Lancet publication noted.
Key point: 0.5 mg/kg identified as minimum effective dose with fewer AEs vs 2.5 mg/kg; single-day infusion feasible.
Implication:Could inform practice and payer discussions; interpretation depends on study design and confounding control.
💊 Orforglipron bests oral semaglutide at 52 wks (ACHIEVE-3) [9] [18 Sep 2025]
Context: Phase 3 head-to-head in T2D on metformin; orforglipron 12/36 mg vs oral semaglutide 7/14 mg.
Key point: Reported superiority on A1C and weight; additional CV risk factor improvements; GI AEs mostly mild-moderate.
Implication: May influence prescriber choice and payer reviews pending full data.
🧴 Verapamil SR in recent-onset T1D (Ver-A-T1D) [10] [EU • 19 Sep 2025]
https://www.eurekalert.org/news-releases/1098672
Context: EU multicenter RCT; SR verapamil 360 mg daily vs placebo; 12-month C-peptide primary.
Key point: Primary narrowly missed; per-protocol showed significant beta-cell preservation signals; safety consistent (first-degree AV block, bradycardia reversible).
Implication: Could inform practice and payer discussions; interpretation depends on study design and confounding control.
Why it matters
- Oral/weekly metabolic therapies keep expanding: head-to-head data (orforglipron) and pediatric outcomes (tirzepatide) may shift treatment algorithms.
- China’s first dual GCG/GLP-1 approval (mazdutide) broadens class competition and access dynamics in a major T2D market.
- T1D disease-modifying avenues (low-dose ATG; verapamil) suggest accessible, repurposed options worth further testing.
- EASD’s diabetes-distress guideline elevates emotional health to routine care, pushing systems toward integrated screening/support.
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FAQ
What exactly did the FDA flag in the MDMA CRL?
Abuse-related AE under-reporting, lack of durability beyond 18 weeks, and selection bias from prior MDMA users; FDA suggests design and safety reporting fixes that do not preclude approvability [2].
How is mazdutide different from GLP-1s already on market?
It’s a dual glucagon/GLP-1 receptor agonist; Phase 3 showed superior HbA1c and weight effects vs controls in Chinese T2D populations and is now approved by China’s NMPA [7].
Did tirzepatide show pediatric benefits strong enough for label expansion?
SURPASS-PEDS met primary/secondary endpoints with A1C and BMI improvements vs placebo; Lilly notes submissions, but timing/outcome not stated here [5].
Is orforglipron ready to replace oral semaglutide?
ACHIEVE-3 reports superiority on A1C and weight at 52 weeks; full peer-review and labels will guide uptake, but the head-to-head positions it competitively [9].
What dose of ATG does MELD-ATG support?
0.5 mg/kg as a minimum effective dose with better tolerability vs 2.5 mg/kg, enabling single-day infusion in recent-onset T1D [8].
Should clinicians change management for isthmus thyroid nodules now?
Not yet. The observational data show higher-risk features, but experts call for validation before altering surgical approaches [3].
Entities / Keywords
Atom Therapeutics; ABP-745; Gout flares; Lykos Therapeutics; MDMA (midomafetamine); FDA CRL; EASD; Diabetes distress guideline; Eli Lilly; Tirzepatide (Mounjaro); Pediatric T2D; Lonapegsomatropin (SKYTROFA); Pediatric GHD; Innovent Biologics; Mazdutide; Dual GCG/GLP-1; ATG (anti-thymocyte globulin); MELD-ATG; Verapamil SR; Ver-A-T1D; Orforglipron; Oral semaglutide.
References
- https://www.businesswire.com/news/home/20250915080338/en/Atom-Therapeutics-Enrolls-First-Patient-in-Multicenter-Global-Phase-2-Trial-of-ABP-745-for-Acute-Gout-Flares
- https://www.hcplive.com/view/fda-releases-crl-detailing-safety-concerns-mdma-assisted-therapy-ptsd
- https://www.medcentral.com/endocrinology/thyroid/thyroid-nodules-in-the-isthmus-are-more-likely-to-be-malignant
- https://medicaldialogues.in/amp/diabetes-endocrinology/guidelines/easd-issues-first-ever-global-clinical-practice-guideline-on-diabetes-distress-155403
- https://www.fiercepharma.com/pharma/lillys-mounjaro-primed-expansion-kids-10-17-type-2-diabetes
- https://www.hcplive.com/view/lonapegosmatropin-for-treatment-of-pediatric-ghd-reduces-overall-us-health-plan-costs
- https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-received-approval-from-chinas-nmpa-for-glycemic-control-in-adults-with-type-2-diabetes-302561434.html
- https://www.news-medical.net/news/20250919/New-findings-support-low-dose-ATG-to-delay-progression-of-type-1-diabetes.aspx
- https://mexicobusiness.news/health/news/orforglipron-surpasses-oral-semaglutide-52-week-diabetes-study
- https://www.eurekalert.org/news-releases/1098672