Metformin on the Presence of COVID-19 Symptoms Over 6 Months: The ACTIV-6 Randomized Clinical Trial.

Background: The effect of metformin on preventing long-term COVID-19 symptoms among low-risk adults has not been studied. The objective of this study was to Assess metformin compared with placebo during acute SARS-CoV-2 infection on the presence of COVID-19 symptoms 180 days later.

Methods: The ACTIV-6 platform evaluated repurposed medications for mild to moderate COVID-19.

Metformin and Time to Sustained Recovery in Adults With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of metformin on reducing symptom duration among outpatient adults with COVID-19 has not been studied.

Objective: To assess metformin compared with placebo for symptom resolution during acute infection with SARS-CoV-2.

Design, Setting, And Participants: The Accelerating COVID-19 Therapeutic Interventions and Vaccines platform evaluated repurposed medications for mild to moderate COVID-19.

The Choice of Viral Load End Point in Early Phase Trials of COVID-19 Treatments Aiming to Reduce 28-Day Hospitalization and/or Death.

Background: Virologic end points are used in phase 2 trials for COVID-19 therapeutics, but they have not been established as surrogates for clinical end points. No meta-analysis using individual participant data (IPD) has been undertaken to identify viral load outcomes for which treatment effects are best associated with effects on hospitalization/death.

Methods: This meta-analysis combined IPD from 23 COVID-19 treatment versus control comparisons to calculate R2, a surrogacy measure quantifying the relationship between the treatment effect on 28-day hospitalization/death and the treatment effect on the surrogate.

Impact of COVID-19 Diagnosis on Weight Trajectories of Children in the US National COVID Cohort Collaborative.

Background: The COVID-19 pandemic has exacerbated the obesity epidemic, with both adults and children demonstrating rapid weight gain during the pandemic. However, the impact of having a COVID-19 diagnosis on this trend is not known.

Methods: Using longitudinal data from January 2019 to June 2023 collected by the US National Institute for Health's National COVID Cohort Collaborative (N3C), children (age 2-18 years) with positive COVID-19 test results (n=11,474, 53% male, mean [SD] age 5.

Impact of COVID-19 Diagnosis on Weight Trajectories of Children in the US National COVID Cohort Collaborative.

The COVID-19 pandemic has exacerbated the obesity epidemic, with both adults and children demonstrating rapid weight gain during the pandemic. However, the impact of having a COVID-19 diagnosis on this trend is not known. Using longitudinal data from January 2019 to June 2023 collected by the US National Institute for Health's National COVID Cohort Collaborative (N3C), children (age 2-18 years) with positive COVID-19 test results { = 11,474, 53% male, mean [standard deviation (SD)] age 5.

Opportunities for General Internal Medicine to Promote Equity in Obesity Care.

The number and complexity of obesity treatments has increased rapidly in recent years. This is driven by the approval of new anti-obesity medications (AOMs) that produce larger degrees of weight loss than previously approved AOMs. Unfortunately, access to these highly effective therapies and to integrated team-based obesity care is limited by intra-/interpersonal patient, institutional/practitioner, community, and policy factors.

SARS-CoV-2 infection is associated with intestinal permeability, systemic inflammation, and microbial dysbiosis in hospitalized patients.

Coronavirus disease 2019 (COVID-19) and its associated severity have been linked to uncontrolled inflammation and may be associated with changes in the microbiome of mucosal sites including the gastrointestinal tract and oral cavity. These sites play an important role in host-microbe homeostasis, and disruption of epithelial barrier integrity during COVID-19 may potentially lead to exacerbated inflammation and immune dysfunction. Outcomes in COVID-19 are highly disparate, ranging from asymptomatic to fatal, and the impact of microbial dysbiosis on disease severity is unclear.

Effect of SARS-CoV-2 Infection on Incident Diabetes by Viral Variant: Findings From the National COVID Cohort Collaborative (N3C).

Objective: The coronavirus 2019 (COVID-19) pandemic has evolved over time by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, disease severity, treatment, and prevention. There is evidence of an elevated risk of incident diabetes after COVID-19; our objective was to evaluate whether this association is consistent across time and with contemporary viral variants.

Research Design And Methods: We conducted a retrospective cohort study using National COVID Cohort Collaborative (N3C) data to evaluate incident diabetes risk among COVID-positive adults compared with COVID-negative patients or control patients with acute respiratory illness (ARI).

Financial Incentives and Treatment Outcomes in Adolescents With Severe Obesity: A Randomized Clinical Trial.

Importance: Adolescent severe obesity is usually not effectively treated with traditional lifestyle modification therapy. Meal replacement therapy (MRT) shows short-term efficacy for body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) reduction in adolescents, and financial incentives (FIs) may be an appropriate adjunct intervention to enhance long-term efficacy.

Objective: To evaluate the effect of MRT plus FIs vs MRT alone on BMI, body fat, and cardiometabolic risk factors in adolescents with severe obesity.

Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications.

Background: Observed activity of metformin in reducing the risk of severe COVID-19 suggests a potential use of the anti-hyperglycemic in the prevention of post-acute sequelae of SARS-CoV-2 infection (PASC). We assessed the 3-month and 6-month risk of PASC among patients with type 2 diabetes mellitus (T2DM) comparing metformin users to sulfonylureas (SU) or dipeptidyl peptidase-4 inhibitors (DPP4i) users.

Methods: We used de-identified patient level electronic health record data from the National Covid Cohort Collaborative (N3C) between October 2021 and April 2023.

Framework of the strengths and challenges of clinically integrated trials: An expert panel report.

The limitations of the explanatory clinical trial framework include the high expense of implementing explanatory trials, restrictive entry criteria for participants, and redundant logistical processes. These limitations can result in slow evidence generation that is not responsive to population health needs, yielding evidence that is not generalizable. Clinically integrated trials, which integrate clinical research into routine care, represent a potential solution to this challenge and an opportunity to support learning health systems.

SMART use of medications for the treatment of adolescent severe obesity: A sequential multiple assignment randomized trial protocol.

Background: Severe obesity is a complex, chronic disease affecting nearly 9% of adolescents in the U.S. Although the current mainstay of treatment is lifestyle therapy, pediatric clinical practice guidelines recommend the addition of adjunct anti-obesity medication (AOM), such as phentermine and topiramate.

Strategies used for the COVID-OUT decentralized trial of outpatient treatment of SARS-CoV-2.

The COVID-19 pandemic accelerated the development of decentralized clinical trials (DCT). DCT's are an important and pragmatic method for assessing health outcomes yet comprise only a minority of clinical trials, and few published methodologies exist. In this report, we detail the operational components of COVID-OUT, a decentralized, multicenter, quadruple-blinded, randomized trial that rapidly delivered study drugs nation-wide.

Obesity Management in Adults: A Review.

Importance: Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiovascular disease, sleep disorders, osteoarthritis, and premature death.

Observations: A body mass index (BMI) of 25 or greater is commonly used to define overweight, and a BMI of 30 or greater to define obesity, with lower thresholds for Asian populations (BMI ≥25-27.5), although use of BMI alone is not recommended to determine individual risk.

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain.

Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.

Design, Setting, And Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19.

Metformin for Treatment of Acute COVID-19: Systematic Review of Clinical Trial Data Against SARS-CoV-2.

Background: Observational and preclinical data suggest metformin may prevent severe coronavirus disease 2019 (COVID-19) outcomes.

Purpose: We conducted a systematic review of randomized, placebo-controlled clinical trials of metformin treatment for COVID-19 to determine whether metformin affects clinical or laboratory outcomes in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and present a structured summary of preclinical data.

Study Selection: Two independent reviewers searched PubMed, Scopus, Cochrane COVID-19 Study Register, and ClinicalTrials.

Metformin reduces SARS-CoV-2 in a Phase 3 Randomized Placebo Controlled Clinical Trial.

Current antiviral treatment options for SARS-CoV-2 infections are not available globally, cannot be used with many medications, and are limited to virus-specific targets. Biophysical modeling of SARS-CoV-2 replication predicted that protein translation is an especially attractive target for antiviral therapy. Literature review identified metformin, widely known as a treatment for diabetes, as a potential suppressor of protein translation via targeting of the host mTor pathway.

Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial.

Background: Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID.

Methods: We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA.