JEWJITSU PEPTIDES: New Methods in Glycoconjugation, Orforglipron’s Renal Questions, and Incretin Updates for MASH

A Science Advances report describes a heterogeneous metallaphotocatalytic approach that embeds nickel catalytic centers within a photoactive covalent organic framework to drive direct, site‑selective thioglycosylation of unprotected thiosugars. The work explains an energy‑transfer mechanism that directly excites transient thiosugar–nickel complexes rather than relying on conventional redox pathways, and demonstrates stereocontrolled coupling to a range of substrates including amino acids and bioactive peptides. The authors report a high turnover frequency (114 per hour) and good catalyst recyclability, and they describe the first heterogeneous photocatalytic glycosylation of the antimicrobial peptide mastoparan with a reported enhancement of its antitumor activity. The paper frames the method as a potentially versatile tool for precision bioconjugation in chemical biology and drug discovery, while presenting experimental scope within the reported examples.

A review in the American Journal of Nephrology examines orforglipron, described as the first oral non‑peptide GLP‑1 receptor agonist, and summarizes available Phase 3 trial data and registry information. The authors report that Phase 3 studies showed reductions in hemoglobin A1c, body weight, and cardiovascular risk markers with stable eGFR and no signals of major renal toxicity in those trials. However, they emphasize that these trials were not designed or powered to evaluate renal endpoints such as eGFR decline, albuminuria, and progression to kidney failure, and that patients with advanced chronic kidney disease were often underrepresented or excluded. The review notes a currently registered trial addressing kidney and cardiovascular outcomes in patients with atherosclerosis and CKD, and calls for dedicated CKD‑specific studies to determine renal safety, efficacy, and potential integration into nephrology practice.

A Digestion article reviews incretin‑based strategies for metabolic dysfunction‑associated steatotic liver disease and its progressive form, MASH. The authors summarize mechanistic rationale—weight reduction, improved insulin sensitivity, and pleiotropic effects on inflammation and lipid metabolism—and report that Phase 2 trials of GLP‑1 receptor agonists show consistent improvement in steatohepatitis, while dual agonists such as tirzepatide provide encouraging signals for fibrosis improvement. Interim Phase 3 data with semaglutide are presented as showing clinically meaningful benefits in MASH resolution and fibrosis regression, and the review notes that semaglutide has received accelerated regulatory approval for non‑cirrhotic MASH with F2–F3 fibrosis. The authors underline that longer‑term outcome data are needed to confirm durability, safety, and effects on major liver‑related outcomes, and they identify remaining evidence gaps.