Peptide research, regulation, discovery. Every story links to the peptide it’s about.
RSSAcross 34,956 EudraVigilance reports filed January 2022 to September 2024 for six GLP-1 receptor agonists, semaglutide carried about half tirzepatide's per-report rate of thyroid cancer events (reporting odds ratio 0.54, P less than 0.05). The sensitivity analysis stratified by indication wiped the signal out.
A 62-patient real-world cohort in Athens started type-2-diabetes adults with fatty liver on dulaglutide, dapagliflozin, or a DPP-4 inhibitor for 12 months. Dulaglutide moved left ventricular global longitudinal strain 22.6 percent. Dapagliflozin moved it 8.5 percent. The DPP-4 inhibitor moved it 5.9 percent. P=0.015.
A 45-patient prospective study split type-2-diabetes adults by prior dapagliflozin use, then started both groups on a GLP-1 receptor agonist. By week 12, the dapagliflozin-naive arm had lost SDNN, SDANN, RMSSD, pNN50, and high-frequency power. The dapagliflozin-on-board arm had not. Four indices stayed significantly separated after covariate adjustment.
A propensity-matched real-world cohort from the TriNetX network (1,728 pairs, 71 healthcare organizations, 2016 to 2025) found 1-year all-cause mortality of 3.4 percent on GLP-1 receptor agonists versus 9.4 percent off them in adults with asymptomatic intracranial atherosclerotic stenosis. Hazard ratio 0.35. Ischemic stroke ran 4.4 percent vs 6.1 percent (HR 0.70). The matching list included HbA1c, LDL, BMI, and systolic blood pressure. The signal persisted anyway.
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.
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.
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 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.
A propensity-matched Neurosurgery cohort of 3,185 IIH patients with BMI 40 or higher found bariatric surgery delivered greater early symptom relief than GLP-1 receptor agonists. Persistent papilledema was more than four times as likely in the GLP-1 arm at 3 to 18 months. Past 18 months, the headline outcomes converged and only tolerability still separated the arms.