GLP-1 receptor agonists were initially developed to treat type 2 diabetes and have had a transformative effect on its therapy, and are highly effective for glycaemic control, with the added benefit of bodyweight reduction and a low risk of causing hypoglycaemia. GLP-1 receptor agonists reduce risks for major adverse cardiovascular events (eg, non-fatal myocardial infarction, stroke, and cardiovascular death), and the risk of admission to or treatment within hospital for heart failure. These drugs reduce albuminuria and slow the decline in estimated glomerular filtration rate over time, therefore delaying or preventing kidney failure. Furthermore, GLP-1 receptor agonists (eg, liraglutide and semaglutide) and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor co-agonist tirzepatide have been approved for treatment of obesity, with clinical trials establishing benefits for various obesity-related conditions: prevention of type 2 diabetes; risk for major adverse cardiovascular events; heart failure, especially with preserved ejection fraction; regression of steatosis and prevention of fibrosis in steatotic liver disease; and symptomatic improvements in obstructive sleep apnoea and knee osteoarthritis. Current developments include the exploration of novel indications (eg, neurodegenerative diseases and substance use disorders) with suggestive evidence of efficacy, and the development of small-molecule GLP-1 receptor agonists for oral treatment to improve convenience. Dual (ie, GLP-1-glucagon and GLP-1-amylin) and triple (ie, GIP-GLP-1-glucagon) receptor agonists activating multiple receptors promise greater efficacy than mono-agonists, especially for weight loss. However, some clinical development programmes have a high burden of adverse gastrointestinal events, and dose-escalation regimens should be optimised to reach acceptable tolerability.

Tetanus, although preventable by a highly effective vaccine, continues to cause 30 000-50 000 deaths annually. Global mortality has fallen substantially since the 1980s due to widespread vaccination efforts, yet adult disease persists, especially among those with weakened immune response, diabetes, and people who inject drugs. Diagnosis is still clinical, and management combines wound debridement, antibiotics, and antitoxin. However, key questions about prevention, diagnosis, and management remain unanswered. Recent trials suggest human and equine antitoxin perform equally, but shortages and high costs persist. Autonomic instability, once thought a late stage complication, is now defined early in the disease course, affecting the prognosis. Due to patients being in intensive care, complications such as nosocomial infections can increase the burden of the disease, reinforcing that vaccination, surveillance, equitable access, and new therapy options are vital.

The effects of small, realistic changes in physical activity and sedentary behaviour on population-level mortality are unclear. We aimed to estimate the proportion of deaths preventable by 5-min and 10-min incremental increases in moderate-to-vigorous intensity physical activity (MVPA) and 30-min and 60-min reductions in daily sedentary time.

Savolitinib combined with osimertinib is a potential novel therapy for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) harbouring MET amplification after progression on EGFR tyrosine kinase inhibitor (TKI) therapy. We aimed to evaluate the efficacy and safety of savolitinib-osimertinib versus standard of care platinum-based doublet chemotherapy in this patient population.

WHO recommends fractional dose vaccination to address yellow fever vaccine shortages during outbreaks. In adults, a 500 IU dose has recently been shown to be non-inferior to the full standard dose, but the minimum effective dose for children is unknown.

Despite highly effective vaccines against SARS-CoV-2, COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic, with rates and motivations for hesitancy varying by demographic group. Addressing the drivers of vaccine hesitancy through targeted interventions in hesitant groups is a public health priority for better and more rapid control of disease spread. We aimed to characterise the determinants and subtypes of vaccine hesitancy and identify more persistent forms of hesitancy via analysis of vaccine uptake in a large cross-sectional cohort with linked National Health Service (NHS) data.

In patients with coronary artery disease, diabetes increases the risk of restenosis and adverse cardiovascular events after percutaneous coronary intervention (PCI). The Abluminus DES+ is a thin-strut cobalt-chromium sirolimus-eluting stent (SES) with abluminal and balloon-surface coating intended to enhance drug delivery to the vessel wall. We aimed to compare the efficacy and safety of the Abluminus DES+ SES versus the XIENCE durable-polymer everolimus-eluting stent (EES) in patients with diabetes undergoing PCI.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a monogenic disease of adulthood characterised by treatment-refractory systemic inflammation and progressive bone marrow failure. VEXAS syndrome is caused by acquired mutations in the UBA1 gene that are restricted to haematopoietic cells. Men aged 50 years or older are particularly susceptible to VEXAS syndrome, with prevalence estimates of approximately one in 4000 men. Perturbation of UBA1, the master enzyme of cellular ubiquitination, promotes myeloid-driven inflammation that is difficult to control with medications other than glucocorticoids. Cytokine-directed therapies (ie, IL-6 and JAK inhibitors) might temporise symptoms and allow glucocorticoid reduction. Hypomethylating agents (ie, azacytidine) can induce clinical and molecular remission in some patients, but are associated with substantial toxicities. Haematopoietic cell transplant might be effective treatment in patients who are suitable candidates. The discovery of VEXAS syndrome highlights the potential role of somatic mutations in complex inflammatory diseases.