Metformin on Risk of Post-Covid Disease 2019 Condition Among Overweight Individuals or Obese: A Population-based Retrospective, 2025, Chaichana et al

[Mij]

Abstract​

Background
A subgroup analysis of the COVID-OUT trial's long-term outcome found that starting metformin within 3 days of coronavirus disease 2019 (COVID-19) diagnosis reduced post–COVID-19 condition (PCC) incidence by 63% in overweight or obese individuals. However, its generalizability remains uncertain.

Objectives
To evaluate the effectiveness of metformin in preventing PCC in adults with overweight or obesity who had a recent COVID-19 infection.

Design
A retrospective cohort study using a sequential target trial emulation framework.

Data Sources
The United Kingdom primary care data from the Clinical Practice Research Datalink Aurum database from March 2020 to July 2023.

Participants
Adults with overweight or obesity (body mass index ≥ 25 kg/m²) and a record of severe acute respiratory syndrome coronavirus 2 infection were included. Exclusions included metformin use in the prior year or metformin contraindications.

Measurements
The outcome was PCC, defined by a PCC diagnostic code or at least 1 World Health Organization–listed symptoms between 90 and 365 days after diagnosis, with no prior history of the symptom within 180 days before infection. The pooled hazard ratio and risk difference for the incidence of PCC were adjust for baseline characteristics.

Results
Among 624 308 patients, 2976 initiated metformin within 90 days of COVID-19 diagnosis. The 1-year risk difference for PCC in the intention-to-treat analysis was −12.58% (hazard ratio 0.36; 95% CI, 0.32–0.41), with consistent results in subgroup analyses.
LINK

 

[Yann04]

This is the study being replicated:

Trial Report Thread 'Outpatient treatment of Covid-19 and the development of Long Covid..., 2023, Bramante et al'

Dec 25, 2022

Edit: Paper now published
Post with abstract here.

Outpatient Treatment of COVID-19 and the Development of Long COVID Over 10 Months: A Multi-Center, Quadruple-Blind, Parallel Group Randomized Phase 3 Trial
Link (Open access to full paper)


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Preprint abstract

Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up

Spoiler: Authors: University of Minnesota and other US centres

Carolyn T Bramante, John B Buse, David Liebovitz, Jacinda Nicklas, Michael A Puskarich, Ken Cohen, Hrishikesh Belani...

• SNT Gatchaman
• fluvoxamine glucose ivermectin long covid metabolism metformin obesity platelets
• Replies: 35
• Forum: Long Covid research

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[Yann04]

I wonder how much this retrospective analysis stands. Given that those who took metformin is likely not random and more those at higher risk or more aware of LC. Though I guess that would push towards a smaller not bigger effect. I guess this data has a lot more confounders than the original study.

Second, to evaluate the influence of unmeasured confounding, we performed a negative control outcome analysis using cancer diagnoses occurring 90–365 days after COVID-19 diagnosis as the outcome. A recent systematic review and meta-analysis of randomized controlled trials found that metformin did not significantly reduce cancer incidence in individuals with overweight/obesity, prediabetes, or diabetes [28], aligning with our study population characteristics. Additionally, a previous target trial emulation study reported no association between metformin use and reduced cancer risk [29]. Given the lack of strong evidence linking metformin to cancer incidence, we selected cancer as a negative control outcome to detect potential biases. Because metformin is unlikely to influence cancer development within the study period, any observed effects on PCC can be more confidently attributed to metformin rather than residual confounding or metabolic effects.

Additionally, we replicated the study using a traditional cohort design, initiating follow-up at 90 days after SARS-CoV-2 diagnosis to validate our results. Our study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies [30]. All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, North Carolina).

 

[Yann04]

We don’t have a S4ME thread for this but this is another study finding Metformin associated with lower PCC prevalence (retrospective)

Prevalent Metformin Use in Adults With Diabetes and the Incidence of Long COVID: An EHR-Based Cohort Study From the RECOVER Program - PubMed

Prevalent metformin use is associated with a slightly lower incidence of death or PASC after SARS-CoV-2 infection. PASC incidence by computable phenotype is higher than by EHR code, especially in PCORnet. These data are consistent with other observational analyses showing prevalent metformin is...

pubmed.ncbi.nlm.nih.gov