Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

Importance In China diabetes prevalence has increased substantially in recent decades, but there are no reliable estimates of the excess mortality currently associated with diabetes. Objective To assess the proportional excess mortality associated with diabetes, and to estimate the diabetes-related absolute excess mortality in rural and urban China. Design, setting, and participants A 7-year nationwide prospective study of 512,869 adults aged 30-79 years from 10 (5 rural, 5 urban) localities across China, recruited from 6/2004 to 7/2008 and followed until 1/2014. Exposure Diabetes (previously diagnosed or screen-detected) recorded at baseline. Main outcome measures All-cause and cause-specific mortality, collected through established death registries. Cox regression was used to estimate adjusted mortality rate ratios (RRs) comparing those with versus without diabetes at baseline. Results Overall, the mean (SD) age was 51.5 (10.7) years, 59% (n=302,618) were women, and 5.9% (n=30,280) had diabetes (rural 4.1%, urban 8.1%, men 5.8%, women 6.1%, previously diagnosed 3.1%, screen-detected 2.8%). During 3.64 million person-years of follow-up, there were 24,909 deaths, including 3,384 among individuals with diabetes. Compared to adults without diabetes, individuals with diabetes had a significantly increased risk of all-cause mortality (1373 vs 646 deaths per 100,000; adjusted RR, 2.00 [95%CI, 1.93 to 2.08]), which was higher in rural than urban areas (rural RR, 2.17 [95%CI 2.07 to 2.29]; urban RR, 1.83 [95%CI, 1.73 to 1.94]). Presence of diabetes was associated with increased mortality from ischaemic heart disease (3287 deaths; RR, 2.40 [95%CI, 2.19 to 2.63]), stroke (4444 deaths; RR, 1.98 [95%CI, 1.81 to 2.17]), chronic liver disease (481 deaths; RR, 2.32 [95%CI, 1.76 to 3.06]), infections (425 deaths; RR, 2.29 [95%CI, 1.76 to 2.99]), and cancer of the liver (1325 deaths; RR, 1.54 [95%CI 1.28 to1.86]), pancreas (357 deaths; RR, 1.84 [95%CI, 1.35 to 2.51]), female breast (217 deaths; RR, 1.84 [95%CI, 1.24 to 2.74]), and female reproductive system (210 deaths; RR, 1.81 [95%CI, 1.20 to 2.74]). For chronic kidney disease (365 deaths), the RR was higher in rural than urban areas (18.69 [95%CI, 14.22 to 24.57] versus 6.83 [95%CI, 4.73 to 9.88]). Among those with diabetes, 10% of all deaths (rural 16%, urban 4%) were due to definite or probable diabetic ketoacidosis or coma (408 deaths). Conclusions and relevance Among adults in China, diabetes was associated with increased mortality from a range of cardiovascular and non-cardiovascular diseases. Although diabetes was more common in urban areas, it was associated with a greater excess mortality in rural areas.

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Diabetes is a common cause of chronic kidney disease (CKD), but in aggregate, non-diabetic diseases account for a higher proportion of cases of CKD than diabetes in many parts of the world. Inhibition of the renin–angiotensin system reduces the risk of kidney disease progression and treatments that lower blood pressure (BP) or low-density lipoprotein cholesterol reduce cardiovascular (CV) risk in this population. Nevertheless, despite such interventions, considerable risks for kidney and CV complications remain. Recently, large placebo-controlled outcome trials have shown that sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduce the risk of CV disease (including CV death and hospitalization for heart failure) in people with type 2 diabetes who are at high risk of atherosclerotic disease, and these effects were largely independent of improvements in hyperglycaemia, BP and body weight. In the kidney, increased sodium delivery to the macula densa mediated by SGLT-2 inhibition has the potential to reduce intraglomerular pressure, which may explain why SGLT-2 inhibitors reduce albuminuria and appear to slow kidney function decline in people with diabetes. Importantly, in the trials completed to date, these benefits appeared to be maintained at lower levels of kidney function, despite attenuation of glycosuric effects, and did not appear to be dependent on ambient hyperglycaemia. There is therefore a rationale for studying the cardio-renal effects of SGLT-2 inhibition in people at risk of CV disease and hyperfiltration (i.e. those with substantially reduced nephron mass and/or albuminuria), irrespective of whether they have diabetes.