Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial
et al., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2021.100142 (date from earlier preprint), TOGETHER, NCT04727424 (history)
, Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with.., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2021.100142 (date from earlier preprint), TOGETHER, NCT04727424
See also
report 34 events for ER/hospitalization.RCT with 215 patients treated with metformin and 203 controls, showing no significant difference with treatment.For multiple major issues with this trial see [doyourownresearch.substack.com, doyourownresearch.substack.com (B)].The hospitalization risk for off-protocol patients was several times higher in both arms, resulting in Simpson's paradox when combining per-protocol and off-protocol patients [twitter.com].750mg twice daily for 10 days.Although the 27% lower mortality is not statistically significant, it is consistent with the significant 32% lower mortality [27‑37%] from meta analysis of the 49 mortality results to date.
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risk of death, 26.6% lower, RR 0.73, p = 0.53, treatment 7 of 215 (3.3%), control 9 of 203 (4.4%), NNT 85, day 28.
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risk of hospitalization, 5.6% lower, RR 0.94, p = 0.88, treatment 24 of 215 (11.2%), control 24 of 203 (11.8%), NNT 152, ITT.
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risk of hospitalization, 39.1% lower, RR 0.61, p = 0.28, treatment 8 of 168 (4.8%), control 14 of 179 (7.8%), NNT 33, PP.
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risk of extended ER observation or hospitalization, 14.0% higher, RR 1.14, p = 0.58, treatment 34 of 215 (15.8%), control 28 of 203 (13.8%), ITT, primary outcome.
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risk of extended ER observation or hospitalization, 12.0% lower, RR 0.88, p = 0.72, treatment 14 of 168 (8.3%), control 17 of 179 (9.5%), NNT 86, PP.
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risk of ER visit, 31.0% lower, RR 0.69, p = 0.48, treatment 8 of 216 (3.7%), control 11 of 205 (5.4%), NNT 60, ITT.
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risk of ER visit, 25.9% lower, RR 0.74, p = 0.62, treatment 7 of 171 (4.1%), control 10 of 181 (5.5%), NNT 70, PP.
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risk of no viral clearance, 1.0% lower, RR 0.99, p = 0.85, treatment 215, control 203, adjusted per study.
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| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Reis et al., 31 Aug 2021, Double Blind Randomized Controlled Trial, Brazil, peer-reviewed, 23 authors, impossible data, see notes, trial NCT04727424 (history) (TOGETHER).
Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial
doi:10.17605/OSF.IO/EG37X)
Background Observational studies have postulated a therapeutic role of metformin in treating COVID-19. We conducted an adaptive platform clinical trial to determine whether metformin is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting. Methods The TOGETHER Trial is a placebo-controled, randomized, platform clinical trial conducted in Brazil. Eligible participants were symptomatic adults with a positive antigen test for SARS-CoV-2. We enroled eligible patients over the age of 50 years or with a known risk factor for disease severity. Patients were randomly assigned to receive either placebo or metformin (750 mg twice daily for 10 days or placebo, twice daily for 10 days). The primary outcome was hospitalization defined as either retention in a COVID-19 emergency setting for > 6 h or transfer to tertiary hospital due to COVID-19 at 28 days post randomization. Secondary outcomes included viral clearance at day 7, time to hospitalization, mortality, and adverse drug reactions. We used a Bayesian framework to determine probability of success of the intervention compared to placebo.
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j. lana.2021.100142.
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