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.