Orforglipron was non-inferior to insulin glargine for MACE-4 in adults with type 2 diabetes at increased cardiovascular risk, establishing its cardiovascular safety in the event-driven ACHIEVE-4 trial. Gastrointestinal adverse events were the most frequent adverse event and the most common reason for orforglipron discontinuation, while clinically significant hypoglycaemia occurred less often with orforglipron than with insulin glargine. The findings support orforglipron as a once-daily oral option with established cardiovascular safety in this population.
The first controlled study presented at the EADV 2026 Congress found nail detachment in 39% of 575 GLP-1 users, more than four times the rate in 1,329 untreated diabetes/obesity controls (9%); nail discoloration affected 46% versus 17% of controls. After adjusting for confounders, detachment and discoloration remained two to three times more common among users. In the same cohort, hair loss and scalp inflammation were also more frequent among users. The cross-sectional design shows association only, not causation.
Regeneron reported Phase II data (N=975) at the EASD meeting and in The Lancet: trevogrumab combined with semaglutide reduced lean mass loss by about 50% by DXA and muscle volume loss by about 70% by MRI.
Combining Eli Lilly's Zepbound with eloralintide, an amylin-targeting candidate, produced 23.3% weight loss at 48 weeks in people with obesity and type 2 diabetes at the highest dose, outperforming Zepbound alone (14.8%) and eloralintide alone (11.1%). High discontinuation rates may raise tolerability questions. It shows next-generation combination therapy can achieve greater weight loss even in patients with diabetes, who typically lose less on medications.
Weekly injections of petrelintide produced roughly 10% weight loss over 42 weeks in the Phase II ZUPREME 1 trial, with a permanent discontinuation rate due to gastrointestinal events of only 1.5%. Results were presented at the EASD annual meeting and published in The Lancet Diabetes & Endocrinology.
Why it matters: The article gives 42-week weight-loss figures by dose and gastrointestinal discontinuation rates that readers can compare directly with real-world GLP-1 discontinuation data.
Retatrutide produced substantial improvements in bodyweight and improved glycaemic control in adults with obesity and type 2 diabetes in the phase 3 TRIUMPH-2 trial, a double-blind, randomised, placebo-controlled comparison. Its safety profile was generally consistent with other molecules with GLP-1 receptor agonism, supporting retatrutide as a possible treatment for obesity in people with type 2 diabetes.
NEJM published Eli Lilly's phase 3 TRIUMPH-1 trial of retatrutide. Among 2339 patients with obesity but without diabetes, after 80 weeks of randomization, the 4 mg/9 mg/12 mg dose groups lost an average of 17.6%/23.7%/25.0% of body weight versus 3.9% with placebo (differences of -19.8 and -21.0 percentage points, both P<0.001).
Low abundance of Akkermansia muciniphila and high leucine levels drive diabetes-associated cognitive decline in diabetic mice and patients. A. muciniphila catabolizes leucine, and excess leucine activates the TBK1-OPTN pathway, enhancing OPTN binding to LC3 and Ub chains and triggering neuronal excessive mitophagy that accelerates cognitive decline in mice. The work identifies a gut-brain metabolic mechanism and a target for gut-directed therapy of cognitive disorders.
In diabetic mice and patients, researchers observed reduced abundance of Akkermansia muciniphila (AKK) alongside elevated leucine levels, and confirmed that AKK can catabolize leucine. Mechanistically, leucine directly regulates TBK1 phosphorylation, which phosphorylates the autophagy adaptor OPTN, enhancing its binding to LC3 and ubiquitin chains and triggering neuronal excessive mitophagy. Leucine supplementation worsens, while leucine restriction alleviates, diabetes-associated cognitive decline, pointing to a new direction for gut-targeted therapy of cognitive disorders.
Why it matters: The paper defines an AKK-leucine-TBK1/OPTN-neuronal excessive mitophagy mechanism chain offering a concrete entry point for gut-targeted intervention in diabetes-associated cognitive impairment.
Microplastics swallowed by mice clog the lysosomes of Kupffer cells, the liver's macrophages, impairing their ability to engulf pathogens and defective cells. The stressed macrophages produce more apolipoproteins, prompting surrounding liver cells to store more fat. Particles the size of an average bacterium were particularly harmful to the liver, while particles 10 times smaller accumulated in brown adipose tissue and stimulated heat production instead.
Roche has discontinued development of a muscle-building drug and ended a trial testing it in combination with an anti-obesity injectable, returning the experimental medicine to Chugai. The move removes one candidate from the muscle-preserving approach to obesity treatment.
An experimental small-molecule inhibitor called GPPD, which blocks the activity of the protein MAP4K4 rather than lowering its expression, reduced fat accumulation, inflammation, liver injury and fibrosis simultaneously in preclinical models of metabolic dysfunction-associated steatohepatitis (MASH). Toxicology studies have so far found no evidence of significant toxicity. The work, published in JHEP Reports, also identified a previously unknown signaling pathway through which MAP4K4 appears to influence disease progression.
AstraZeneca has invested $2 billion in Summit Therapeutics, according to the headline of a STAT+ report. Separately, Novo Nordisk licensed a once-weekly oral GLP-1/GIP receptor agonist for obesity from Hengrui Pharma, paying $300 million upfront for global rights outside China, with total deal value of $2.6 billion if milestones are met; the drug is ready for Phase 1 development.
Novo has agreed a deal worth $2.6 billion with Hengrui for a preclinical GLP-1/GIP drug. Hengrui is described as an in-demand partner in the obesity and metabolic space. No further deal terms or timelines are given.
A liver single-cell atlas of 77 patients with chronic liver disease resolves monocyte-derived, pro-fibrotic macrophages into 2 subpopulations of TREM2+ scar-associated macrophages. The analysis identifies OLR1 as a candidate therapeutic target for selectively modulating pro-fibrotic macrophage functions and thereby attenuating liver fibrosis.
Once-daily oral small-molecule GLP-1 receptor agonist safiglipron reduced HbA1c by up to 1.45% versus placebo over 32 weeks in people with early type 2 diabetes not taking glucose-lowering medication, in the randomized OUTSTAND-1 trial. Body weight effects were modest. It offers an oral option with glycemic efficacy in this population.
A bedside blood test from Aarhus University measures drug concentrations directly in untreated blood in under 10 minutes, versus up to an hour for central laboratory processing. Tested on samples from 52 patients in Denmark and abroad, results matched those of traditional laboratory instruments. The device, costing DKK 30,000-50,000, could let stroke teams quickly check for anticoagulants before giving clot-busting medication, which risks brain hemorrhage in such patients.
Plasma indole-3-propionic acid (IPA) is lower in people with type 2 diabetes than in healthy controls and higher levels are associated with reduced T2D odds. A 7-day broad-spectrum antibiotic intervention, which suppressed gut microbiota in individuals given histidine supplementation, cut IPA to near-undetectable levels in both groups, confirming its microbial origin. IPA also showed a novel inverse correlation with glycemic variability, and was associated with gut microbiota beta diversity rather than any known IPA-producing taxa.
