Does monoclonal antibody treatment for COVID-19 impact short and long-term outcomes in a large generalisable population? A retrospective cohort study in the USA.

OBJECTIVES: To explore whether monoclonal antibodies (MAb) administered to high-risk patients with COVID-19 during the first week of illness prevent postacute sequelae of SARS-CoV-2 infection. DESIGN: Retrospective cohort study. SETTING: USA. PARTICIPANTS: A sample of 3809 individuals who received MAbs and a matched one-to-one comparison group from a set of 327 079 eligible patients who did not receive MAb treatment were selected from a deidentified administrative data set from commercial and Medicare Advantage health plan enrollees in the USA, including claims and outpatient laboratory data. RESULTS: Individuals who received MAb were 28% less likely to be hospitalised (HR=0.72, 95% CI 0.58 to 0.89) and 41% less likely to be admitted to the intensive care unit (HR=0.59, 95% CI 0.38 to 0.89) 30 days from SARS-CoV-2 diagnosis compared with individuals who did not receive MAb. A higher proportion of individuals given MAb therapy received care for clinical sequelae in the postacute phase (p=0.018). CONCLUSIONS: While MAb therapy was associated with benefits in the acute period, the benefit of therapy did not extend into the postacute period and did not reduce risk for clinical sequelae.

Improved Time in Range During 28 Days of Meal Delivery for People With Type 2 Diabetes.

Objective: Nutrition therapy is a cornerstone of care for people with type 2 diabetes, yet starting new, healthy eating behaviors and sustaining them can be challenging. This decentralized, single-arm study assessed the impact of 28 days of home-delivered, pre-portioned meals (three meals per day) on continuous glucose monitoring (CGM)-derived glycemic control and quality of life. Research design and methods: We enrolled 154 people with type 2 diabetes from across the United States. All participants were enrolled in a digital-first type 2 diabetes care center of excellence and had a time in range (TIR) <70% or a glucose management index (GMI) >7%. A total of 102 participants received another set of meals for a household member. Forty-four participants were excluded from CGM-based analysis because of sparse data in the baseline or intervention period. Results: From the baseline through the intervention period, average TIR improved by 6.8% (95% CI 4.0-9.7, P <0.001), average GMI improved by 0.21% (95% CI 0.11-0.32, P <0.001), and participants' odds of achieving ≥70% TIR increased (odds ratio 2.55 [95% CI 0.93-7.80, P = 0.051]). Although average TIR increased rapidly upon initiation of meal delivery, it regressed when the delivery period ended. Conclusion: Home-delivered meals were associated with modest TIR and GMI improvements, but only in the short term. More research is needed to determine whether the effects of nutrition therapy can be extended by providing ongoing meal delivery or additional support such as behavioral intervention.

Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis.

BACKGROUND: Type 2 diabetes and obesity, as states of chronic inflammation, are risk factors for severe COVID-19. Metformin has cytokine-reducing and sex-specific immunomodulatory effects. Our aim was to identify whether metformin reduced COVID-19-related mortality and whether sex-specific interactions exist. METHODS: In this retrospective cohort analysis, we assessed de-identified claims data from UnitedHealth Group (UHG)'s Clinical Discovery Claims Database. Patient data were eligible for inclusion if they were aged 18 years or older; had type 2 diabetes or obesity (defined based on claims); at least 6 months of continuous enrolment in 2019; and admission to hospital for COVID-19 confirmed by PCR, manual chart review by UHG, or reported from the hospital to UHG. The primary outcome was in-hospital mortality from COVID-19. The independent variable of interest was home metformin use, defined as more than 90 days of claims during the year before admission to hospital. Covariates were comorbidities, medications, demographics, and state. Heterogeneity of effect was assessed by sex. For the Cox proportional hazards, censoring was done on the basis of claims made after admission to hospital up to June 7, 2020, with a best outcome approach. Propensity-matched mixed-effects logistic regression was done, stratified by metformin use. FINDINGS: 6256 of the 15 380 individuals with pharmacy claims data from Jan 1 to June 7, 2020 were eligible for inclusion. 3302 (52·8%) of 6256 were women. Metformin use was not associated with significantly decreased mortality in the overall sample of men and women by either Cox proportional hazards stratified model (hazard ratio [HR] 0·887 [95% CI 0·782-1·008]) or propensity matching (odds ratio [OR] 0·912 [95% CI 0·777-1·071], p=0·15). Metformin was associated with decreased mortality in women by Cox proportional hazards (HR 0·785, 95% CI 0·650-0·951) and propensity matching (OR 0·759, 95% CI 0·601-0·960, p=0·021). There was no significant reduction in mortality among men (HR 0·957, 95% CI 0·82-1·14; p=0·689 by Cox proportional hazards). INTERPRETATION: Metformin was significantly associated with reduced mortality in women with obesity or type 2 diabetes who were admitted to hospital for COVID-19. Prospective studies are needed to understand mechanism and causality. If findings are reproducible, metformin could be widely distributed for prevention of COVID-19 mortality, because it is safe and inexpensive. FUNDING: National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Patient-Centered Outcomes Research Institute; Minnesota Learning Health System Mentored Training Program, M Health Fairview Institutional Funds; National Center for Advancing Translational Sciences; and National Cancer Institute.

Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19.

Background Type 2 diabetes (T2DM) and obesity are significant risks for mortality in Covid19. Metformin has been hypothesized as a treatment for COVID19. Metformin has sex specific immunomodulatory effects which may elucidate treatment mechanisms in COVID-19. In this study we sought to identify whether metformin reduced mortality from Covid19 and if sex specific interactions exist. Methods De-identified claims data from UnitedHealth were used to identify persons with at least 6 months continuous coverage who were hospitalized with Covid-19. Persons in the metformin group had at least 90 days of metformin claims in the 12 months before hospitalization. Unadjusted and multivariate models were conducted to assess risk of mortality based on metformin as a home medication in individuals with T2DM and obesity, controlling for pre-morbid conditions, medications, demographics, and state. Heterogeneity of effect was assessed by sex. Results 6,256 persons were included; 52.8% female; mean age 75 years. Metformin was associated with decreased mortality in women by logistic regression, OR 0.792 (0.640, 0.979); mixed effects OR 0.780 (0.631, 0.965); Cox proportional-hazards: HR 0.785 (0.650, 0.951); and propensity matching, OR of 0.759 (0.601, 0.960). TNF-alpha inhibitors were associated with decreased mortality in the 38 persons taking them, by propensity matching, OR 0.19 (0.0378, 0.983). Conclusions Metformin was significantly associated with reduced mortality in women with obesity or T2DM in observational analyses of claims data from individuals hospitalized with Covid-19. This sex-specific finding is consistent with metformin reducing TNF-alpha in females over males, and suggests that metformin conveys protection in Covid-19 through TNF-alpha effects. Prospective studies are needed to understand mechanism and causality.