NEWS.

The European Association for the Study of Obesity updated its living obesity-pharmacotherapy framework. Two cells moved. Tirzepatide is now first-line when weight loss is the goal and the patient has no other complications. Semaglutide is the only drug recommended for improvement in MASH-fibrosis stage. Sixty-two randomized trials behind a society guideline that updated in seven months instead of seven years.

A 1,021-patient propensity-matched cohort found that starting a GLP-1 receptor agonist dropped time in therapeutic range by 2.1 percentage points (p=0.01) and increased time above range by 1.3 points. Mean INR did not shift — variance did. The interaction is behavioral, not pharmacokinetic: appetite suppression makes vitamin K intake variable, and warfarin's narrow window tracks that variability.

A 9-residue cyclic peptide called BLMP6 selectively homes to triple-negative breast cancer metastases in mice. Tagged with gallium-68 it lights up the lungs on PET. Tagged with MMAE it kills the metastatic cells in place. The Kolonin lab also identified the target: fibulin-4, an ECM protein elevated in invasive human breast tumors.

ATTAIN-MAINTAIN, the first phase-3 maintenance trial in obesity, randomized 376 adults who had completed 72 weeks of weekly tirzepatide or semaglutide to daily oral orforglipron or placebo for another year. The pill arm held 74.7 percent of the prior weight loss after tirzepatide and 79.3 percent after semaglutide; the placebo arms held 49.2 percent and 37.6 percent. Blood pressure, lipid, and glucose gains held with the weight.

Chugai reported in Organic Process Research and Development a convergent 24-step liquid-phase synthesis of LUNA18 (paluratide) delivering kilogram-scale GMP material at over 98.5% purity and more than 30% overall yield. The molecule is an N-alkyl-rich cyclic undecapeptide oral pan-RAS inhibitor, binding KRAS, NRAS, and HRAS in both wildtype and mutant forms, with 21-47% oral bioavailability. Phase 1 monotherapy and combination-with-cetuximab dose escalation is underway. The chemistry milestone joins Merck's biocatalytic enlicitide cascade as a second large-pharma macrocyclic-peptide manufacturing answer in two weeks.

A 3,478-patient TriNetX match has GLP-1 receptor agonists beating bariatric surgery on colectomy (OR 0.13), IBD flares (OR 0.44), and seven other outcomes, even though the drug arm finished the study heavier (BMI 34.5 vs 33.4).

Eli Lilly's Mounjaro booked $8.66B in Q1 2026 sales, ahead of Merck's Keytruda at $7.9B, making tirzepatide the world's top-selling pharmaceutical and ending Keytruda's two-year run at #1 (a position the anti-PD-1 antibody had held since displacing Humira in early 2023). The full tirzepatide platform (Mounjaro plus Zepbound) generated $36.5B in 2025 against Keytruda's $31.6B. It is the first time a peptide therapeutic has taken the #1 drug spot since the historical era of insulin biosimilars.

Two ECO 2026 abstracts in Istanbul (May 12-15) are closing the geriatric obesity-drug data gap simultaneously. A Padova-led pooled analysis of semaglutide 2.4 mg in 358 adults aged 65 and older from STEP 1, 3, 4, 5, 8, and 9 reports 15.4% weight loss vs 5.1% placebo, 28.6% hit at least 20% loss vs 2.7%, and 27% reached a healthy BMI under 27. A Lilly post-hoc analysis of orforglipron pools 616 adults aged 65 and older from ATTAIN-1 and ATTAIN-2, the first proper geriatric pool for an oral GLP-1 product. Both peptide and pill are getting their first systematic 65+ read in the same week.

MBX Biosciences reported Phase 2a STEADI proof-of-concept for once-weekly imapextide in post-bariatric hypoglycemia on May 11, with glucose nadir up 17-34% and insulin peak down 11-45% across doses. Same GLP-1 receptor antagonist mechanism as Amylyx's avexitide (Phase 3 LUCIDITY readout Q3 2026), same indication. The PBH peptide space went from single-drug curiosity to two-program race overnight. The same MBX update covered MBX 4291 once-monthly Phase 1 data and the IND-enabling amycretin candidate MBX 5765, both engineered for monthly dosing.

A JAMA Network Open retrospective cohort of 841,831 women with breast cancer (TriNetX, 68 healthcare orgs, 10-year follow-up) found GLP-1 receptor agonists associated with lower mortality and recurrence-free survival vs propensity-matched comparators. Hazard ratios were 0.35 (mortality) in the obesity subgroup vs nonusers and 0.09 vs insulin/metformin in T2D. The third comparison, GLP-1 RAs vs SGLT2 inhibitors, found no significant difference, arguing against any GLP-1-specific anti-cancer mechanism and pointing toward the shared metabolic-class benefit.

Amylyx opened a US Expanded Access Program on May 5 for up to 250 adults with post-bariatric hypoglycemia, providing access to avexitide while LUCIDITY reads out topline in Q3 2026. Avexitide is the first-in-class peptide GLP-1 receptor antagonist (the same molecule as exendin (9-39), a truncated form of exendin-4 that binds without activating). FDA Breakthrough Therapy Designation in both PBH and congenital hyperinsulinism. The program inverts the GLP-1 narrative: for this population, GLP-1 signaling is the problem.

Vertex Pharmaceuticals' Q1 2026 update confirmed multiple-ascending-dose enrollment in GALILEO, the Phase 1/2 study of VX-670 in adults with myotonic dystrophy type 1, with results guided for H2 2026. VX-670 is an oligonucleotide linked to a cyclic peptide from Entrada's EEV cell-penetrating-peptide platform, engineered to displace MBNL1 from toxic CUG-repeat RNA and correct downstream missplicing. Same platform that produced 2.36% dystrophin restoration in Entrada's DMD Phase 1/2 in May. DM1 has no disease-modifying therapy.

Rhythm Pharmaceuticals reported Q1 2026 results May 5 that pulled in opposite directions: Imcivree (setmelanotide) net revenue of $60.1M (+59% YoY) on the acquired hypothalamic obesity launch and EU authorization, while the EMANATE Phase 3 program in genetically caused MC4R-pathway diseases missed its primary endpoint in all four independent substudies. The MC4R agonist class works in the indications it is approved for and does not generalize to heterozygous-variant populations the way the program had hoped.

Merck published a Science paper on May 7 introducing a biocatalytic cascade for the manufacture of enlicitide, an oral PCSK9 inhibitor in Phase 3 with -55.8% LDL-C reported earlier in 2026. A suite of engineered enzymes handles fragment formation, peptide coupling, and macrocyclization in a protecting-group-free sequence, with crystallizations replacing chromatography. Step count drops by more than half versus prior state-of-the-art. The methodology generalizes beyond enlicitide to the broader macrocyclic peptide drug class facing CDMO bottlenecks.

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.