NEWS.

A 2025 Nature paper from Stanford's Svensson lab introduces BRP, a 12-amino-acid peptide cleaved from BRINP2 by prohormone convertases that suppresses food intake by activating POMC neurons through a leptin-, GLP-1R-, and MC4R-independent pathway. ~50% food-intake reduction in minipigs within one hour, 3-4 g fat loss in obese mice over 14 days, no nausea, no GI distress, no muscle-mass loss. The Peptide Predictor AI scan of 2,600+ prohormone cleavage products is the discovery-methodology story.

An Am J Case Rep paper reports moderate-to-severe cutaneous allodynia in two severe-obesity patients on tirzepatide for weight management, with onset during dose escalation, severity tracking dose, and resolution after discontinuation. The first published case series specifically linking tirzepatide to allodynia, joining the broader GLP-1 sensory side-effect cluster (Wegovy HD dysesthesia, Ozempic Face) the section has tracked.

Entrada Therapeutics announced May 7 that ENTR-601-44, a first-in-class Endosomal Escape Vehicle peptide-PMO conjugate, produced a 2.36% mean dystrophin increase from a 4.00% baseline at 6 mg/kg in Cohort 1 of the ELEVATE-44-201 Phase 1/2 trial in Duchenne muscular dystrophy. Time-to-Rise velocity improved significantly with clean safety. The 6 mg/kg dose is well below the 30 mg/kg standard for unconjugated PMOs.

An ACR Open Rheumatology study in 60,198 patients with rheumatic and musculoskeletal diseases tracks GLP-1 RA initiation from 0.1% in 2018 to 6.8% in 2024. At 12 months, tirzepatide users lost 8.2% body weight versus 5.8% for semaglutide users (treatment difference 2.2 percentage points, CI 1.9-2.5). Non-diabetic patients lost 1.8% more weight than those with diabetes.

A new Archives of Pharmacal Research meta-analysis of 14 RCTs and 1,260 non-diabetic patients with Alzheimer's disease, Parkinson's disease, or mild cognitive impairment finds GLP-1 RAs produce only a trivial improvement in global cognition (SMD 0.14, high-certainty) and a moderate decrement in verbal fluency (SMD -0.43, high-certainty). The first quantitative challenge to the GLP-1-as-neurodegenerative-therapy hypothesis.

A Nature paper from the international TransCODE Consortium identifies 1,785 previously unrecognized microproteins from non-canonical open reading frames, expanding the human proteome by approximately 10%. Based on meta-analysis of 95,520 proteomics experiments, the work codifies 'peptideins' as a working category for microproteins with indeterminate functional potential. The paper sets the reference annotation standard for ncORF-encoded microproteins.

A multinational retrospective cohort in Neurology reports that calcitonin gene-related peptide inhibitors (Aimovig, Vyepti, Ajovy, Emgality, atogepant, rimegepant) reduce incident glaucoma risk by 25% over 3 years versus non-CGRPi migraine preventives (HR 0.75, CI 0.61-0.92). The protective effect concentrates in the monoclonal antibody subclass and persists across older adults, women, chronic migraine, and migraine-without-aura subgroups.

An Am J Respir Cell Mol Biol paper describes NTyP-100, a nanocarrier conjugating a peptide inhibitor of non-muscle myosin light chain kinase with a sphingosine-1-phosphate analogue. In two rodent acute lung injury models (LPS one-hit in mice, LPS plus mechanical ventilation two-hit in rats), the construct cut inflammatory injury by approximately 40% compared with either component alone, with attenuation of TNF, IL-17, and apoptosis pathway dysregulation.

A Canadian Journal of Anesthesia meta-analysis of 10 prospective studies and 300 patients quantifies the GLP-1 receptor agonist gastric-emptying delay at a mean of 74 minutes (95% CI 46-101). Short-acting agents (exenatide, lixisenatide) push the delay to 116 minutes; the first 10 weeks of therapy sit at 82 minutes. The result quantifies the mechanism behind ASA's 2023 perioperative hold guidance.

A new Nature Communications umbrella review pools 123 meta-analyses spanning 464 outcomes from 5,617 articles into a unified evidence map. Benefits cluster across endocrine, cardiovascular, renal, respiratory, and cognitive domains plus selected-population mortality and fracture-risk reductions. Risks concentrate in diabetic retinopathy, ketoacidosis, gastrointestinal events, and treatment discontinuation. Most comprehensive synthesis of the GLP-1 class to date.

A 26-week Lancet RCT in 108 patients with moderate-to-severe alcohol use disorder and comorbid obesity reports that once-weekly semaglutide 2.4 mg reduced heavy drinking days by 41.1 percentage points from baseline versus 26.4 on placebo. Treatment difference: -13.7 percentage points (p = 0.0015). First adequately powered randomized confirmation of the GLP-1 effect on alcohol use that preclinical and observational data have predicted for years.

A Nature Communications paper from the University of Manchester replaces the natural 425-kDa NRPS that assembles the ACV tripeptide precursor for penicillin biosynthesis with a standalone glutathione-style ligase plus an epimerase. An engineered isopenicillin N synthase then produces penicillin G, penicillin V, and ampicillin directly, sidestepping the semisynthesis steps current industrial production requires.

A 2025 Vanderbilt volumetric imaging study referenced in a new Endocrine review puts Ozempic Face at roughly 9% midface volume loss per 10 kilograms of GLP-1-driven weight loss, concentrated in the superficial and medial cheek fat pads. AAFPRS reports a 50% year-over-year increase in face-grafting procedures tied to the trend. Mechanistic data point to a possible direct effect on adipose-derived stem cells, beyond rapid lipolysis.

A Discover Oncology paper builds a proteolysis-targeting chimera with a 13-amino-acid BCL6-binding peptide (F1324) and pomalidomide-derived cereblon recruiters loaded onto lipid nanoparticles. The construct selectively degraded BCL6, inhibited DLBCL proliferation in vitro and in vivo, and showed clean safety in normal tissues. Peptide warheads expand the PROTAC addressable target space; LNP delivery makes the peptide approach pharmacologically tractable.

A new American Journal of Cardiology meta-analysis of 8 RCTs and 11,234 patients shows GLP-1 receptor agonists reduce HF worsening events by 33% in heart failure with preserved ejection fraction (HR 0.67, high-certainty), with consistent benefits across NT-proBNP, six-minute walk distance, KCCQ score, and blood pressure. In HFrEF, no benefit was observed (HR 1.23, moderate-certainty). The split is patient-selection guidance, not a generic class effect.