Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The International Diabetes Federation : losing its credibility by partnering with Nestle?

The International Diabetes Federation (IDF) is an umbrella organisation of more than 200 national diabetes associations in over 160 countries, and states its mission as being “to promote diabetes care, prevention and a cure worldwide”. In pursuing this mission, it can proudly point to many highly successful initiatives, helping to raise awareness, advocate for and guide clinical and public health action, and to build alliances for the prevention and control of diabetes and other chronic non-communicable diseases (NCDs) worldwide. Unfortunately its partnering with Nestlé, announced on Nestlé's website at the end of April,1 is in our view a serious misjudgment, the long-term effect of which will be contrary to IDF's mission and bad for public health

Diabetes management and treatment approaches outside of North America and West Europe in 2006 and 2015

Aims The impact of introducing new classes of glucose-lowering medication (GLM) on diabetes management remains unclear, especially outside North America and Western Europe. Therefore, we aimed to analyse trends in glycaemic control and the usage of new and old GLMs in people with type 2 diabetes from 2006 to 2015. Methods Summary data from clinical services from nine countries outside North America and Western Europe were collected and pooled for statistical analysis. Each site summarized individual-level data from out-patient medical records for 2006 and 2015. Data included: demographics; HbA1c and fasting plasma glucose levels; and the proportions of patients taking GLM as monotherapy, combination therapy and/or insulin. Results Between 2006 and 2015, glycaemic control remained stable, although body mass index and duration of diabetes increased in most sites. The proportion of people on GLM increased, and the therapeutic regimens became more complex. There were increases in the use of insulin and triple therapy in most sites, while monotherapy, particularly in relation to sulphonylureas, decreased. Despite the introduction of new GLMs, such as DPP-4 inhibitors, insulin use increased over time. Conclusions There was no clear evidence that the use of new classes of GLMs was associated with improvements in glycaemic control or reduced the reliance on insulin. These findings were consistent across a range of economic and geographic settings.Fil: Tabesh, Maryam. Monash University; Australia. Baker Heart and Diabetes Institute; AustraliaFil: Magliano, Dianna J.. Monash University; Australia. Baker Heart and Diabetes Institute; AustraliaFil: Tanamas, Stephanie K.. Baker Heart and Diabetes Institute; AustraliaFil: Surmont, Filip. Astrazeneca; Reino UnidoFil: Bahendeka, Silver. Uganda Martyrs University; Uganda. St. Francis Hospital Nsambya; UgandaFil: Chiang, Chern En. Taipei Veterans General Hospital; ChinaFil: Elgart, Jorge Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Kalra, Sanjay. Bharti Research Institute of Diabetes and Endocrinology; IndiaFil: Krishnamoorthy, Satheesh. Dr A Ramachandran’s Diabetes Hospitals; IndiaFil: Luk, Andrea. Prince of Wales Hospital Hong Kong; Hong KongFil: Maegawa, Hiroshi. Shiga University of Medical Science; JapónFil: Motala, Ayesha A.. University of KwaZulu Natal; SudáfricaFil: Pirie, Fraser. University of KwaZulu Natal; SudáfricaFil: Ramachandran, Ambady. Dr A Ramachandran’s Diabetes Hospitals; IndiaFil: Tayeb, Khaled. Diabetes Center at Al-Noor Specialist Hospital; Arabia SauditaFil: Vikulova, Olga. FGBU “Endocrinology Research Center” Ministry of Health; RusiaFil: Wong, Jencia. University of Sydney; AustraliaFil: Shaw, Jonathan E.. Baker Heart and Diabetes Institute; Australia. Monash University; Australi