Research coverage runs from preclinical mechanism papers to AI-driven peptide discovery. Most of what shows up here lives in Nature, Cell, Science, JAMA, and the abstracts from AACR, ESCMID, AAN, and ESCMID Global.
A few threads keep recurring. Macrocyclic and bicyclic peptides keep getting better at hitting "undruggable" targets — KRAS, beta-catenin, intracellular protein–protein interactions. Antimicrobial peptides have moved from theory to clinical candidates against carbapenem-resistant organisms and biofilms. Cancer peptide vaccines (ELI-002, autogene cevumeran, EVX-01) are producing real survival data. AI design tools — protein language models, transformer architectures, de novo platforms — are starting to generate hits that humans wouldn't.
If you want the lab side without the press releases, this is the right surface. The stories below name the lab, the journal, and the result.
An ORION indirect treatment comparison presented at ECO 2026 on May 13 framed the head-to-head competition between Novo's Wegovy pill (oral semaglutide 25 mg) and Lilly's Foundayo (orforglipron 36 mg). The Wegovy pill delivered statistically significant greater mean weight loss than orforglipron, with patients on orforglipron showing approximately 14x higher odds of discontinuing treatment due to gastrointestinal side effects. The May 13 framing complements Novo's Q1 print disclosure that Wegovy holds 65% of all new US GLP-1 prescriptions; CEO Mike Doustdar's CNBC commentary called the moment a 'turnaround situation' for the Danish company. The ORION ITC matters as a prescriber-decision tool given the two compounds are now the only two FDA-approved oral GLP-1s for chronic weight management.
A Frontiers in Bioinformatics review published March 17, 2026 from Tope Abraham Ibisanmi and colleagues at UNSW Sydney documents how computational antimicrobial peptide discovery has collapsed from decades to weeks. The review covers big-data mining, molecular dynamics simulations, and AI methods that capture complex sequence-activity relationships and predict novel AMPs from genomic and metagenomic data. The headline example: one large language model approach produced 18 de novo peptides of which 17 were active (94.4% hit rate) over a 48-day discovery cycle. The framing complements the broader AMP-as-AMR-response thesis with Aifeity, the University of Bonn, and Cesar de la Fuente at Penn — and lands as Cesar de la Fuente's Penn lab launches new generative AMR molecules into ESKAPE-pathogen testing.
Real-world data presented in the ECO 2026 cycle counters the trial-based efficacy headlines: a Prime Therapeutics commercial claims analysis (cited in the May 2026 Managed Healthcare Executive cover story) found just 8.1% of members persisted with anti-obesity GLP-1 medications for three years. A separate 6-month Medicaid persistence analysis showed roughly 61% staying on treatment at six months. The high attrition is driven primarily by GI tolerability, insurance turnover, and out-of-pocket costs after step-edit programs. For newer agents like semaglutide and tirzepatide, post-discontinuation weight regain averages 0.8 kg per month — projecting return to baseline by ~1.5 years. PBM programs (Optum Rx Weight Engage, Rightway, MedImpact GLP-1 Benefit 360) are now embedding multidisciplinary support to lift persistence above the current floor.
Joelle Pelletier's perspective in Science (volume 392, pages 582-583, published online May 8) accompanies the Merck enlicitide biocatalytic synthesis paper and frames the enzyme-cascade route — engineered enzymes plus chromatography-free crystallization to cut step count by more than half — as a template that goes well beyond enlicitide. The piece argues that the limiting step for oral macrocyclic peptide therapeutics has been the manufacturing cost of multi-step protected-residue chemistry, not pharmacology or pharmacokinetics; biocatalysis collapses the cost curve and unlocks a pipeline of oral peptides at large molecular weights that have been quietly stuck in preclinical or Phase 1 economics. The framing matters as enlicitide (oral PCSK9 inhibitor with 57% LDL-C reduction at 24 weeks) heads toward NDA filing.
Prof. John Wilding (University of Liverpool) and colleagues will present at ECO 2026 a real-world observational study tracking obesity-linked complication rates by degree of GLP-1-driven weight loss. In the year following GLP-1 treatment initiation, 27.0% of patients had BMI reductions <5%, 22.4% had 5-<10%, 14.1% had 10-<15%, 15.8% had ≥15%, and 20.8% gained BMI. Over a mean 11-month follow-up, patients with ≥15% BMI reduction had 37% lower osteoarthritis odds, 30% lower CKD odds, 69% lower OSA odds, and 32% lower heart failure odds versus those with 0-5% reduction (all statistically significant except heart failure). Incidence per 1,000 person-years: 21.4 OA, 21.1 CKD, 20.3 OSA, 3.9 HF. The data quantifies the value of pushing for deeper weight loss rather than cruise-control dosing.
TIDES USA 2026 opens in Boston May 11-14 with a featured presentation on Chugai's LUNA18 (paluratide), an N-alkyl-rich cyclic undecapeptide oral KRAS inhibitor. The corresponding paper in Organic Process Research & Development describes a convergent 24-step liquid-phase synthesis route delivering kilogram-scale GMP material at >98.5% purity and >30% overall yield. LUNA18 binds KRAS, NRAS, and HRAS mutants plus wildtype, inhibiting the inactive-state RAS-GEF protein-protein interaction; it achieves 21-47% oral bioavailability without special formulation. The molecule is in Phase 1 monotherapy and combination-with-cetuximab dose escalation. LUNA18's chemistry is a milestone for the oral-cyclic-peptide-against-intracellular-targets thesis that Bicycle Therapeutics, Circle Pharma, and Unnatural Products are advancing through different platform architectures.
Rice University assistant professor Erin Standen and colleagues at the Mayo Clinic (Sean Phelan) and UCLA (Janet Tomiyama) published in the International Journal of Obesity on May 5 a study finding that adults who lose weight via GLP-1 receptor agonists like Ozempic and Wegovy face more judgment than those who lose weight through diet and exercise — or who do not lose weight at all. The stigma framing centers on 'easy way out' perceptions and intensifies if the patient later regains weight. The work joins the broader social-context literature shaping the GLP-1 era — including the Ozempic Face plastic-surgery surge, GLP-1-related shame disclosures, and patient-reported drift away from disclosing medication use to friends and family.
A Frontiers in Drug Discovery review (April 10, 2026) catalogs underexplored peptide-receptor systems that the authors argue failed not for biological reasons but because of technical and conceptual barriers solvable with modern peptide engineering. Coverage spans metabolic and energy-balance peptides (apelin, spexin), appetite-regulating systems (peptide YY, oxyntomodulin), bone-muscle-fat crosstalk mediators (osteocalcin, irisin), and neuroendocrine-immune-metabolic peptides (phoenixin, relaxin-3). The argument: lessons from GLP-1 — stabilization, conjugation, and dosing innovation — now make these orphan receptor systems tractable. Companion essay from Bloomgarden in the Journal of Diabetes (2026, vol 18 e70204) frames the same opportunity from the clinical side, citing GLP-1 tolerability ceilings and the 10-20% non-responder problem that creates room for the next wave.
A Nature paper published May 6 from a University of Virginia team developed humanized GLP1R mouse models to investigate how small-molecule GLP1R agonists — including orforglipron (Foundayo) — regulate feeding behavior. Beyond canonical hypothalamic and hindbrain networks that control metabolic homeostasis, the team showed these oral compounds recruit a discrete population of Glp1r-expressing neurons in the central amygdala and selectively suppress consumption of palatable foods by reducing dopamine release in the nucleus accumbens — a parallel hedonic-feeding circuit distinct from the homeostatic mechanism that drives most GLP-1 weight loss. The work explains why patients on small-molecule oral GLP-1s often report reduced food cravings and pleasure-driven eating, and identifies a neural circuit with implications for substance-use disorder and binge eating beyond obesity.
A 2026 scoping review in the Journal of Cachexia, Sarcopenia and Muscle catalogs peptides studied as therapeutic candidates and biomarkers in skeletal muscle wasting — covering sarcopenia, cancer cachexia, and ICU-related atrophy. The review documents MIF1/MIF2 myostatin peptide inhibitors, cachexia-targeting platform peptides, and the broader role of GH-axis peptides (CJC-1295, ipamorelin, tesamorelin) in muscle homeostasis. The clinical urgency lands harder now than it did pre-2024: Nature Reviews Endocrinology recently flagged sarcopenia and frailty as under-recognized GLP-1 receptor agonist side effects, with up to 40% of GLP-1-induced weight loss attributable to lean mass in the highest-loss patients. The review surfaces non-GLP-1 peptide candidates that could be paired with incretin therapy to protect muscle.
Bloomgarden's commentary in the Journal of Diabetes (2026, vol 18, e70204) frames the clinical case for moving past first-generation GLP-1 agonists, focusing on two limits: gastrointestinal intolerance that forces dose reduction or discontinuation in 15-30% of patients depending on agent and titration, and a non-responder problem where roughly 10-20% of treated individuals fail to reach the expected weight-loss range. With 12% of US adults reported to have at least temporarily received a GLP-1 agonist, the population-level stakes are large. The commentary lands alongside the Frontiers Drug Discovery 'Beyond GLP-1' review as one of two academic pieces this month formalizing the post-incretin research agenda — and aligns with the AstraZeneca ASCEND triple-mechanism thesis, the petrelintide + enicepatide combination program, and Lilly's quintuple agonist disclosed for ADA 2026.
Merck scientists published in Science a convergent biocatalytic synthesis of enlicitide decanoate, an investigational oral PCSK9 inhibitor and macrocyclic peptide. A tailored suite of engineered enzymes catalyzes selective peptide fragment formation, coupling, and macrocyclization in a protecting-group-free sequence; combined with chromatography-free crystallizations, the route reduces step count by more than half versus prior state-of-the-art methods. Enlicitide is in Phase 3 (CORALreef, with –55.8% LDL-C reported earlier in 2026) and would be the first oral PCSK9 inhibitor if approved. The paper matters beyond enlicitide: protein-engineering-led cascades shift the cost basis for any large macrocyclic peptide program facing peptide-CDMO bottlenecks.
A Nature Communications paper (2026) introduces CycloPepper, a machine-learning-guided platform for predicting cyclization outcomes and accelerating automated synthesis of therapeutic cyclic peptides. The model addresses one of the persistent bottlenecks in cyclic-peptide drug development: many promising linear sequences fail at the macrocyclization step or yield poorly under standard conditions, requiring expensive iterative chemistry. CycloPepper trains on a curated dataset of cyclization outcomes and integrates with automated synthesis platforms to enable closed-loop design-make-test cycles. The work joins CyclicMPNN (a fine-tuned ProteinMPNN derivative for cyclic peptide sequence design) and AfCycDesign as part of a fast-maturing computational stack for cyclic-peptide therapeutics.
A March 2026 bioRxiv preprint reports an AI-guided strategy for the discovery of cyclic peptide antagonists targeting the CD28 immune checkpoint, with the lead candidate CIP-3 binding the CD28 extracellular domain at nanomolar affinity and producing controllable modulation in cellular assays. CD28 is the principal T-cell co-stimulatory receptor and a high-value target for autoimmunity and transplantation, where current biologics (abatacept, belatacept) are large fusion proteins with associated dosing and immunogenicity tradeoffs. CIP-3's small cyclic-peptide format opens the prospect of subcutaneous dosing with a different PK profile. The work illustrates how AI-driven cyclic-peptide design is expanding beyond GLP-1 mimetics into immune-checkpoint pharmacology.
A May 2026 Drug Discovery World feature consolidates the case for cyclic peptides as a distinct therapeutic modality: larger and more selective than small molecules, more permeable and cheaper to manufacture than antibodies, and uniquely suited for protein-protein-interaction targets that have resisted traditional drug discovery. The piece traces the recent algorithmic stack — RFDiffusion adaptations for cyclic backbones, AfCycDesign, ProteinMPNN-derived sequence design — alongside the synthesis chemistry advances (one-pot ligations, photo-redox macrocyclizations) that turn computational hits into tractable scaffolds. Over 40 cyclic peptide drugs are now FDA-approved across endocrine, oncology, and antimicrobial uses, and 6+ peptide-drug conjugates sit in Phase 3, per the late-April PDC market analysis.
Pharmacy Times ran a Ferry Ossendorp Q&A on May 5 walking through the mechanistic case for peptide-based cancer vaccines: T cells recognize small peptides presented on the surface of tumor cells, and synthetic peptides matched to tumor antigens can be used to vaccinate the immune system to recognize and target those tumors. Ossendorp's own work showed that knowledge of a tumor's antigen profile combined with peptide vaccination can protect against very aggressive tumors in animal models. The piece sits inside a 2026 peptide-vaccine pipeline with 31 active personalized cancer-vaccine trials registered (more than dendritic-cell or RNA-vaccine platforms), the BioVaxys MVP-S survivin program heading to ASCO 2026, the Greenwich GP2/GLSI-100 FLAMINGO-01 readout, and the BriaCell Bria-IMT Phase 3.
The international TransCODE Consortium published a Nature paper May 6 reporting that roughly 25% of 7,264 non-canonical open reading frames (ncORFs) give rise to detectable peptides, based on a meta-analysis of 95,520 proteomics experiments. The work identifies 1,785 previously unrecognized microproteins, expands the human proteome by ~10%, and introduces the conceptual model of 'peptideins' — microproteins with indeterminate functional potential. Most peptideins are under 50 amino acids and lack similarity to traditional proteins. The consortium, launched in 2022, includes GENCODE, PeptideAtlas, HUPO-HPP, and HUPO-HIPP and aims to set the reference annotation standard for ncORF-encoded microproteins.
A 2026 Frontiers in Aging review consolidates the case for therapeutic peptides as gerontology agents, mapping mechanisms across mitochondrial-derived peptides (MOTS-c, humanin), thymic peptides (thymosin alpha-1), wound-and-tissue-repair peptides (BPC-157, TB-500), copper peptides (GHK-Cu), and growth-hormone secretagogues (CJC-1295, ipamorelin). The review frames the longevity peptide field as a clinical category that now sits alongside GLP-1 metabolic medicine — driven by Hims & Hers' 2026 longevity-specialty launch, Drexel's May 5 Q&A on peptide popularity, and the FDA Category 2 removal of 12 peptides on April 22. The piece also flags that BPC-157, TB-500, and most wellness peptides still lack published human RCTs, with clinical use largely based on case reports and preclinical mechanistic rationale.