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Association Between Prevalent Metformin Use and the Incidence of Long COVID in Adults With Type 2 Diabetes
TAKE-HOME MESSAGE
- This retrospective cohort analysis evaluated the association between prevalent metformin use prior to SARS-CoV-2 infection and the incidence of its postacute sequelae in adults with type 2 diabetes. Prevalent metformin use was associated with a lower incidence of death or postacute sequelae of SARS-CoV-2 infection within 180 days after SARS-CoV-2 infection than the use of other diabetes medications.
- There may be a beneficial role for metformin use in adults with type 2 diabetes following SARS-CoV-2 infection.
abstract
This abstract is available on the publisher's site.
Access this abstract nowOBJECTIVE
Studies show metformin use before and during SARS-CoV-2 infection reduces severe COVID-19 and postacute sequelae of SARS-CoV-2 (PASC) in adults. Our objective was to describe the incidence of PASC and possible associations with prevalent metformin use in adults with type 2 diabetes mellitus (T2DM).
RESEARCH DESIGN AND METHODS
This is a retrospective cohort analysis using the National COVID Cohort Collaborative (N3C) and Patient-Centered Clinical Research Network (PCORnet) electronic health record (EHR) databases with an active comparator design that examined metformin-exposed individuals versus nonmetformin-exposed individuals who were taking other diabetes medications. T2DM was defined by HbA1c ≥6.5 or T2DM EHR diagnosis code. The outcome was death or PASC within 6 months, defined by EHR code or computable phenotype.
RESULTS
In the N3C, the hazard ratio (HR) for death or PASC with a U09.9 diagnosis code (PASC-U09.0) was 0.79 (95% CI 0.71-0.88; P < 0.001), and for death or N3C computable phenotype PASC (PASC-N3C) was 0.85 (95% CI 0.78-0.92; P < 0.001). In PCORnet, the HR for death or PASC-U09.9 was 0.87 (95% CI 0.66-1.14; P = 0.08), and for death or PCORnet computable phenotype PASC (PASC-PCORnet) was 1.04 (95% CI 0.97-1.11; P = 0.58). Incident PASC by diagnosis code was 1.6% metformin vs. 2.0% comparator in the N3C, and 2.1% metformin vs. 2.5% comparator in PCORnet. By computable phenotype, incidence was 4.8% metformin and 5.2% comparator in the N3C and 24.7% metformin vs. 26.1% comparator in PCORnet.
CONCLUSIONS
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 associated with favorable outcomes after SARS-CoV-2 infection in adults with T2DM.
Additional Info
Prevalent Metformin Use in Adults With Diabetes and the Incidence of Long COVID: An EHR-Based Cohort Study From the RECOVER Program
Diabetes Care 2024 Nov 01;47(11)1930-1940, SG Johnson, S Abedian, T Stürmer, JD Huling, C Lewis V, JB Buse, SB Brosnahan, PC Mudumbi, KM Erlandson, GA McComsey, J Arnold, TD Wiggen, R Wong, S Murphy, C Rosen, R Kaushal, MG Weiner, C BramanteFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The postacute sequelae of SARS-CoV-2 infection (PASC), also called long COVID, is an important consequence of COVID-19 that can impair the quality of life and clinical health of patients. Type 2 diabetes (T2D) is associated with an increased risk of developing PASC; however, to date, there is no specific therapy for this condition.
The aim of this retrospective cohort analysis was to evaluate the effect of metformin use versus the use of other diabetes medications prior to SARS-CoV-2 infection in patients with T2D on the incidence of PASC. The investigators used data from two large electronic health record (EHR)–based research networks: the National COVID Cohort Collaborative (N3C) and the National Patient-Centered Clinical Research Network (PCORnet). The cohort included adults aged 21 years or older who were diagnosed with T2D prior to their first diagnosis of COVID-19 and received diabetes treatment within the previous 12 months. The outcome of interest was the diagnosis of PASC or death within 180 days of the diagnosis of COVID-19 because death precludes a diagnosis of PASC. In conclusion, adults with T2D who were treated with metformin had a lower risk of death or developing PASC within 180 days after SARS-CoV-2 infection than those treated with other diabetes medications.
These findings are consistent with other studies that showed the protective effects of metformin use against adverse COVID-19 outcomes, probably because of its pleiotropic effects against SARS-CoV-2. Therefore, metformin can inhibit mTOR, thereby reducing viral translation during acute SARS-CoV-2 infection and mitigating the inflammatory cascade that leads to PASC.
However, this study has several limitations. For example, it is impossible to know whether the observed effect is dose-dependent, or to assess patients' compliance with their prescribed medication regimen. Moreover, the two databases used different algorithms to determine the probability of PASC. Overall, metformin use can slightly lower the incidence of death or PASC in individuals with T2D.