How a cheap diabetes pill could impact sales of Pfizer's COVID antiviral Paxlovid

With Pfizer saying in January that it expects a huge decline in revenue for its COVID-19 antiviral pill Paxlovid, sales could be impacted in the future by an unlikely medicine: metformin, the long-used drug for diabetes.

While combinations of drugs have long been used in clinical practice to produce better efficacy through synergistic results, metformin, one of the first medicines doctors turn to for diabetes, may be a headscratcher. But it shouldn't necessarily be.

That's because mounting research indicates that Paxlovid and metformin could improve outcomes related to Long COVID, a chronic illness that could potentially fell millions of those who have gotten COVID.

Metformin might also spur use of Paxlovid -- especially if its found to have synergistic effects -- since many individuals are unwilling to take it due to reports of side effects and a COVID rebound effect, though it's unclear if metformin mitigates the rebound.

Given its cheap price especially compared to Paxlovid, metformin could eventually become a COVID treatment, even without being taken with Paxlovid. Although research on metformin for COVID looks promising, a great deal more research on the diabetes drug for this indication is needed.

Repurposing Drugs

If metformin eventually achieves wide use as a COVID treatment, it would not be unusual. Many drugs, even after initial approval, are investigated for other purposes, often for conditions completely unrelated to the initial indication, in a process known as repurposing.

A good example is finasteride. While the drug was initially approved for overactive bladder under the name Proscar, it later won approval in a different dosage strength as Propecia for hair loss.

Before Paxlovid, other antivirals, or monoclonal antibodies were authorized by the US FDA to treat COVID, scientists were feverishly working with a plethora of existing meds to see if any might work against COVID. Among the more notable ones were the antiparastic drug ivermectin and the antidepressant fluvoxamine. Neither has shown conclusive evidence of effectiveness against COVID.

Paxlovid is already under investigation in a federal government-funded study of treatments for Long COVID.

The Evidence for Metformin

Although metformin was first discovered in 1922, it wasn't used as a medicine until 1957 in France. Its use in the US didn't begin until 1995. The drug is the most widely used oral therapy for diabetes in the world and the third most prescribed drug in the US, as of 2020.

As to why metformin might be effective against COVID, researchers at Northwestern University say that the drug reduces high blood glucose levels, which are linked to poorer COVID; the drug might also decrease the viral cycle of COVID-19; and it might be able to make it more difficult for SARS-CoV-2, the virus that causes COVID, to enter cells.

The researchers also noted that metformin was used as a flu treatment in the 1940s and 1950s.

The evidence for metformin in COVID so far is promising, but by no means conclusive. A pre-print study in The Lancet published earlier in March headed by researchers at University of Minnesota found that those in the metformin group has a 42% relative decline in the incidence of Long COVID compared to those in the control group. It's important to note, however, that this study has yet to be peer reviewed.

The study, which enrolled just over 1.1K people who were overweight or obese, also examined the use of ivermectin and fluvoxamine in preventing long COVID. It did not.

"Future research is needed to understand optimal dosing regimens for preventing Long Covid, whether extended release is effective in persons who have side effects from immediate release metformin, and whether metformin could be used as a treatment for Long Covid," the researchers wrote. "Future research could also assess whether metformin is effective if started during an emergency department visit or hospitalization for Covid-19."

The same Minnesota researchers previously looked at the three drugs in a similar demographic, those these patients had early symptoms of COVID and weren't hospitalized. Their study, published in the New England Journal of Medicine in August 2022, found that none of the meds led to a decline in emergency department visits, hospitalization, or death compared to a control group. However, those in the metformin group did show possible reduction in a composite endpoint of emergency department visit, hospitalization, or death.

Another study that just came out in JAMA Internal Medicine examined nirmatrelvir, one of the two antiviral meds in Paxlovid (the other is ritonavir), in preventing Long COVID symptoms. Researchers took a look at healthcare databases from the US Veterans Administration to find those who had a positive COVID test result and had a least one risk factor to progress to severe disease.

Results indicated that nirmatrelvir treatment led to a reduced risk of developing Long COVID symptoms, regardless of vaccination status or history of prior infection, compared to the control group.

"When thinking about whether to use Paxlovid or not, we should be thinking about effectiveness in the acute phase but also effectiveness in reducing the long-term complications from COVID infection," co-author Ziyad Al-Aly, chief of research and development at the VA St. Louis Health Care System, told CNN.

Despite the promise of Paxlovid and metformin in treating Long COVID, there are still no study results of taking the two drugs together.

Pfizer's Concerns

In its Q4 and full-year 2022 earnings report released in January, Pfizer (NYSE:PFE) said that Paxlovid generated ~$19B in sales for the year. However, it warned that in 2023, that figure would decline 58% to $8B.

During its earnings call, CEO Albert Bourla conceded that the US government still has an inventory build-up of Paxlovid that will be used up sometime in 2023. In addition, Pfizer (PFE) will likely raise the price of Paxlovid once the COVID public health emergency ends in May.

Bourla painted a more optimistic picture for Paxlovid after 2023, however. "We expect in years 2024 and beyond that the courses sold and used will align closely together within every year."

While the exec said he sees increased utilization of Paxlovid this year due to more infections, the company has not included any new major non-US or non-China contracts in its Paxlovid sales projections.