Background GLP-1 receptor agonists reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes. However, uncertainty regarding kidney outcomes persists and whether benefits extend to exendin-4-based GLP-1 receptor remains uncertain. We aimed to meta-analyse the most up-to-date evidence on the cardiovascular benefits and risks of GLP-1 receptor agonists from outcome trials in

Background Increased mortality in transgender people has been described in earlier studies. Whether this increased mortality is still present over the past decades is unknown. Therefore, we aimed to investigate trends in mortality over five decades in a large cohort of adult transgender people in addition to cause-specific mortality. Methods We did a retrospective cohort study of adult transgender

Background Diabetic ketoacidosis (DKA) has been reported to be increasing in frequency during the COVID-19 pandemic. We aimed to examine the rates of DKA hospital admissions and the patient demographics associated with DKA during the pandemic compared with in prepandemic years. Methods Using a comprehensive, multiethnic, national dataset, the Secondary Uses Service repository, we extracted all emergency

Background Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR). Methods In this

The first insulin preparation capable of consistently lowering blood glucose was developed in 1921. But 100 years later, blood glucose control with insulin in people with diabetes is nearly universally suboptimal, with essentially the same molecule still delivered by the same inappropriate subcutaneous injection route. Bypassing this route with oral administration appears to have become technologically

Type 1 diabetes is characterised by autoimmune-mediated destruction of pancreatic β-cell mass. With the advent of insulin therapy a century ago, type 1 diabetes changed from a progressive, fatal disease to one that requires lifelong complex self-management. Replacing the lost β-cell mass through transplantation has proven successful, but limited donor supply and need for lifelong immunosuppression

Adrenal myelolipomas are benign, lipomatous tumours with elements of myeloid cells, most of which present as adrenal incidentalomas and comprise 3·3–6·5% of all adrenal masses. Adrenal myelolipomas are usually unilateral (in 95% of cases), variable in size, most often found during midlife, and affect both sexes almost equally. On imaging, adrenal myelolipomas show pathognomonic imaging features consistent

Background Semaglutide is an effective treatment for type 2 diabetes; however, 20–30% of patients given semaglutide 1·0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea. Methods We did a 40-week

Background Cardiovascular disease is the main determinant of premature mortality in patients with type 1 diabetes. However, time trends regarding different types of cardiovascular disease in childhood-onset type 1 diabetes with a long timespan from the diagnosis of diabetes are not well established. This study aimed to investigate the cumulative incidence of cardiovascular disease in individuals with

Background COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. Methods DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with

Background Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk. Methods In this randomised, double-blind, placebo-controlled, phase 4, single centre trial, we enrolled community-dwelling

Osteoporotic or fragility fractures affect one in two women and one in five men who are older than 50. These events are associated with substantial morbidity, increased mortality, and an impaired quality of life. Recommended general measures for fragility fracture prevention include a balanced diet with an optimal protein and calcium intake and vitamin D sufficiency, together with regular weight-bearing

Childhood, adolescent, and young adult cancer survivors are at increased risk of reduced bone mineral density. Clinical practice surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could improve bone mineral density parameters and prevent fragility fractures. Discordances across current late effects guidelines necessitated international harmonisation of

Background Diabetes is a major risk factor for erectile dysfunction, however, the effect of GLP-1 receptor agonists on erectile dysfunction is unknown. We aimed to assess the incidence, prevalence, and progression of erectile dysfunction in men treated with dulaglutide compared with placebo, and to determine whether dulaglutide's effect on erectile dysfunction was consistent with its effect on other

Background Oncogenic alterations in RET represent important therapeutic targets in thyroid cancer. We aimed to assess the safety and antitumour activity of pralsetinib, a highly potent, selective RET inhibitor, in patients with RET-altered thyroid cancers. Methods ARROW, a phase 1/2, open-label study done in 13 countries across 71 sites in community and hospital settings, enrolled patients 18 years

Background Type 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, and preclinical studies show that it reverses and prevents diabetes. Our aim was to evaluate the safety and efficacy of imatinib in preserving β-cell function in patients with recent-onset type 1 diabetes. Methods We did

Background Nutritional deficiencies, such as iron and vitamin B12 deficiencies, are potential adverse consequences of bariatric surgery. Long-term data on anaemia after bariatric surgery are largely lacking. We aimed to investigate the risk of anaemia, iron and vitamin B12 deficiency anaemia, and vitamin B12 deficiency over 20 years in individuals who had bariatric surgery or received usual obesity

Despite the successful development of new therapies for the treatment of type 2 diabetes, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors, the search for novel treatment options that can provide better glycaemic control and at reduce complications is a continuous effort. The present Review aims to present an overview of novel targets and mechanisms

Background National and global recommendations for BMI cutoffs to trigger action to prevent obesity-related complications like type 2 diabetes among non-White populations are questionable. We aimed to prospectively identify ethnicity-specific BMI cutoffs for obesity based on the risk of type 2 diabetes that are risk-equivalent to the BMI cutoff for obesity among White populations (≥30 kg/m2). Methods

Background Since the EU approval of nitisinone in 2005, prognosis for patients with hereditary tyrosinaemia type 1 has changed dramatically, with patients living with the disease now reaching adulthood for the first time in history. This study aimed to assess the long-term safety and outcomes of nitisinone treatment in patients with hereditary tyrosinaemia type 1. Methods We did a non-interventional

Background With improved treatment, individuals with type 1 diabetes are living longer but there is limited information on the effects of type 1 diabetes on cognitive ability as they become older adults. We followed up individuals with type 1 diabetes to identify independent risk factors for cognitive decline as people age. Methods 1051 participants with type 1 diabetes enrolled in the Diabetes Control

China has experienced many drastic social and economic changes and shifts in people's lifestyles since the 1990s, in parallel with the fast rising prevalence of obesity. About half of adults and a fifth of children have overweight or obesity according to the Chinese criteria, making China the country with the highest number of people with overweight or obesity in the world. Assuming that observed time

The global surges in obesity and nutrition-related non-communicable diseases (NCDs) have created a need for decisive new food policy initiatives. A major concern has been the impact of ultra-processed foods (UPFs) and ultra-processed drinks on weight gain and on the risk of several NCDs. These foods, generally high in calories, added sugar, sodium, and unhealthy fats, and poor in fibre, protein, and

Background There are few long-term studies of interventions to reduce in low socioeconomic status children with overweight or obesity. The Stanford GOALS trial evaluated a 3-year, community-based, multi-level, multi-setting, multi-component (MMM) systems intervention, to reduce weight gain among low socioeconomic status, Latinx children with overweight or obesity. Methods We did a two-arm, parallel

Background Obesity is a major risk factor for adverse outcomes after infection with SARS-CoV-2. We aimed to examine this association, including interactions with demographic and behavioural characteristics, type 2 diabetes, and other health conditions. Methods In this prospective, community-based, cohort study, we used de-identified patient-level data from the QResearch database of general practices

Background Thyroid eye disease manifests inflammation and treatment-resistant proptosis and diplopia. Teprotumumab, an insulin-like growth factor-1 receptor inhibiting monoclonal antibody, was approved in the USA on Jan 21, 2020, on the basis of two randomised trials. In this analysis we evaluated the short-term and long-term aggregate response to teprotumumab from the two trials, focusing on proptosis

Obesity has become a major public health issue in China. Overweight and obesity have increased rapidly in the past four decades, and the latest national prevalence estimates for 2015–19, based on Chinese criteria, were 6·8% for overweight and 3·6% for obesity in children younger than 6 years, 11·1% for overweight and 7·9% for obesity in children and adolescents aged 6–17 years, and 34·3% for overweight

China has one of the largest populations with obesity in the world, and obesity has become a major challenge for the country's health-care system. Current guidelines for obesity management are not adequately supported by evidence from clinical studies in Chinese populations. Effective lifestyle interventions suitable for Chinese populations are scarce, insufficient weight-loss medications have been