Metformin, ivermectin and fluvoxamine may have antiviral activity by inhibiting protein synthesis. To find out whether these drugs can prevent a severe course of Covid-19 infection, researchers conducted a multicenter RCT among overweight or obese adult patients from several US hospitals (N Engl J Med. 2022;387:599- 610). The researchers defined a ‘severe course of covid-19’ as a home oxygen saturation ≤ 93%, presentation to the emergency department, hospitalization or death within 2 weeks of onset of symptoms. They randomized patients within 3 days of proven Covid-19 infection according to a factorial 2-by-3 design between metformin, ivermectin and fluvoxamine. The researchers adjusted for vaccination status and use of other study medications in the analyzes.
The researchers analyzed data from 1431 patients (median age: 46 years; 56% female; 82% white). Neither metformin (adjusted odds ratio (aOR): 0.84; 95% CI: 0.66-1.09) nor ivermectin (aOR: 1.05; 95% CI: 0.76-1.45 ) or fluvoxamine (aOR: 0.94; 95% CI: 0.76-1.45) had an effect on the occurrence of a serious course.
Marloes Dankers, pharmacist at the Institute for Responsible Medicine Use, says in a response: ‘This RCT provides relevant insights about 3 available drugs and their effectiveness in the early phase of a covid-19 infection. The study confirms the lack of efficacy of ivermectin, as previously concluded in a Cochrane Review based on 11 RCTs. Little other research is available for metformin, but the results of the current study give little reason to expect an effect of this drug in a covid-19 infection. Of the 3 substances studied, fluvoxamine is probably the one with the most potency. In a previous systematic review and meta-analysis based on 3 RCTs, a possible effect on the prevention of hospital admissions was found. The dose of fluvoxamine used in these RCTs was higher than in this study. More research into fluvoxamine as a treatment option in the early phase of a covid-19 infection is therefore recommended, both into the mechanism of action and into the clinical effects.’