Table 3.

Health care use outcomes for prospective randomized controlled trials comparing metformin with placebo in individuals with COVID-19

	Need for ED visit	Need for hospitalization	Viral laboratory tests
COVID-OUT (immediate-release metformin with a 6-day titration to 1,500 mg daily)
ITT	NNT = 69	NNT = 53	Not yet reported
	OR 0.67	OR 0.438
mITT	NNT = 60	NNT = 66	Not yet reported
	OR 0.636	OR 0.446
TOGETHER Trial (extended-release metformin initiated at 750 mg twice daily)
ITT	NNT = 61 OR 0.67	NNT = 152 OR 0.94	Time to viral clearance OR 0.99, P = 0.85
Per protocol	NNT = 72	NNT = 33	Time to viral clearance OR 0.98,
	OR 0.73	OR 0.61	P = 0.76
	Need for oxygen†	Duration of hospitalization	Viral laboratory tests
Ventura-López et al.  (metformin glycinate 620 mg twice daily)*	Metformin 5.9 ± 4.6, placebo 10.6 ± 6.2, P = 0.03	Metformin 8.8 ± 6.1 days, placebo 9.8 ± 5.4 days, P = 0.352	Percent reduction in viral load: metformin 93.2 ± 15.4, placebo 78.3 ± 62.7, P = 0.013; days to negative viral load: metformin 3.3 ± 2.16, placebo 5.6 ± 0.89, P = 0.029; percent with negative viral load <3.3 days: metformin 40%, placebo 0, P = 0.043
Health care use (ED visit, hospitalization, or death)
	Overall	Symptom onset to drug initiation <4 days	Symptom onset to drug initiation ≥4 days
COVID-OUT (mITT)	OR 0.58, 95% CI 0.35–0.94	OR 0.45, 95% CI 0.22–0.93	OR 0.75, 95% CI 0.38–1.47
TOGETHER Trial
ITT	OR 1.14, 95% BCI 0.73–1.81	OR 1.36, 95% CI 0.56–3.31	OR 1.62, 95% CI 0.67–3.92
Per protocol	Not reported	Not reported	Not reported
Ventura-López et al.	Not reported	Not reported	Not reported

Data are means ± SD unless otherwise indicated. BCI, Bayesian credible interval.

^*All treated patients: patients who received at least one dose of the study drug and had both basal and later data recorded.

^†Oxygen need point scale. See Ventura-López et al. (28) for details on how this was calculated.