NEWS.

A phase 2a randomized trial at one academic medical center tested semaglutide against placebo in 24 non-treatment-seeking adults who smoke. The two prespecified primary endpoints, lab smoking resistance and cigarettes per session, did not move. Craving and body weight dropped on the drug. The first prospective controlled signal for sema in cigarette use is a null primary, with a directional supplementary analysis and two cleanly positive secondary outcomes.

A new peptide tracer let researchers read TREM2 inside living mouse brains, lighting up an Alzheimer's mouse model by 86 percent and an endotoxin neuroinflammation model by 114 percent. Knockout mice dimmed by 42 percent and confirmed the signal needs the target.

SURPASS-EARLY is the first phase 4 trial to put tirzepatide head-to-head against best-of-current-care instead of placebo or a single comparator. Over two years in 794 adults with early T2D, the tirzepatide arm beat a comparator that was explicitly allowed to use semaglutide, dulaglutide, liraglutide, or any other current option (just not tirzepatide) by 0.68 percentage points of HbA1c, 8.0 kg of body weight, and 6.2 cm of waist circumference, and reached normoglycemia (HbA1c under 5.7 percent) in 60.2 percent vs 24.0 percent.

A preregistered BJPsych Open meta of three placebo-controlled RCTs (N=258) returned an 11.32 kg pooled body-weight loss on semaglutide 1.0-2.0 mg over 26 to 36 weeks. HbA1c fell 0.37 percentage points. The same search found zero tirzepatide trials in a population categorically excluded from STEP, STEP 8, and SURMOUNT-1.

Lilly's once-daily oral GLP-1 small molecule Foundayo hit roughly 17,000 US prescriptions for the week ending May 15, the first weekly print above 15,000 since the April 6 launch. Wegovy pill (oral semaglutide 25 mg) recorded roughly 142,000 in the same week. Three weeks ago the ratio was 20-to-1, and a peptidemodel piece from May 4 framed the gap as more likely to widen than narrow. It has narrowed three weeks running.

Campylobacter jejuni isolates that resist the human cathelicidin LL-37 do not block it or pump it out. They sense it, up-regulate the serine protease HtrA, and cleave the peptide between residues 20 and 21. A two-residue swap on the substrate side closes the loop.

A Sydney case series put nine end-stage heart failure outpatients on semaglutide. All nine cleared the transplant BMI cutoff and were listed; seven were transplanted.

A new classifier called MARC reads cysteine-rich venom peptide sequences and assigns each to a sodium, potassium, calcium, or non-ion-channel bucket. Trained on 5,165 sequences from sea anemones, snakes, scorpions, spiders, cone snails, and terebrid sea snails, it flagged 28 new terebrid teretoxins as potassium-channel candidates and validated one (Cje1.9) by docking and molecular dynamics against KcsA and MthK.

The European Medicines Agency's CHMP on May 22 recommended approval for the once-daily oral Wegovy 25 mg tablet for obesity. The OASIS 4 trial put the pill's mean weight loss at 16.6 percent, in the same range as injectable Wegovy in STEP 1. The label includes SELECT's 20 percent reduction in major heart events, carried over from the injectable. UK, Germany, and Denmark are first in the H2 2026 European launch.

A Cleveland Clinic Taussig analysis of 10,225 GLP-1 receptor agonist users with stage I-III cancer, propensity-matched against 12,115 dipeptidyl peptidase-4 inhibitor users, found that GLP-1 RA exposure cut progression to stage IV by 50 percent in non-small cell lung cancer, 43 percent in breast, 41 percent in colorectal, and 32 percent in hepatocellular carcinoma. Prostate, pancreatic, and renal cell carcinoma trended in the same direction but did not reach significance. The active comparator is the design point: this is GLP-1 vs another T2D drug class, not vs no treatment. ASCO 2026 abstract 3143.

A WHO VigiBase disproportionality analysis published May 22 mapped each GLP-1 receptor agonist to its own paraesthesia subtype. Exenatide tracks with oral numbness, semaglutide and tirzepatide with hyperaesthesia, and semaglutide alone with the burning-skin form.

Eli Lilly's pivotal Phase 3 of retatrutide produced a 28.3 percent mean weight loss at 12 mg over 80 weeks in 2,339 adults with obesity and no diabetes, with 45.3 percent of patients reaching the 30-percent-or-more threshold historically reserved for bariatric surgery. Discontinuation due to adverse events at the top dose was 11.3 percent, roughly double Wegovy or tirzepatide 15 mg. The transient ALT signal from TRIUMPH-4 reappeared but normalized by week 24. The NDA filing waits for TRIUMPH-2 and TRIUMPH-3 later in 2026.

A PLOS Medicine meta-analysis pooled five observational cohorts and put the hazard ratio for nonarteritic anterior ischemic optic neuropathy on semaglutide at 2.17 (95% CI 1.73 to 2.74). The signal held across every comparator the authors tried, but the absolute rate stayed near 0.014% per year, or about one extra case per 7,000 patients per year.

A propensity-matched EHR cohort of 10,048 sleeve and 10,048 liraglutide patients in the Annals of Gastroenterology found Barrett's esophagus in 0.3 percent of sleeve patients versus 0.1 percent of liraglutide patients at three years. The risk ratio was 2.70 (95% CI 1.31-5.56). Cancer rates were rare and did not differ between arms, a window that may simply be too short for an adenocarcinoma signal.

A TriNetX retrospective cohort of 16,176 propensity-matched adults with untreated brain aneurysms found GLP-1 receptor agonists tracked with a 48 percent lower five-year rupture risk. In a separate matched cohort of 298 patients who ruptured, prior GLP-1 use was associated with roughly half the rates of intraparenchymal hemorrhage, intraventricular hemorrhage, and clinically significant vasospasm. The two-tier signal suggests a wall-stabilizing effect rather than a single-outcome shift.