Metformin is back in the spotlight, and not just for its long track record in managing type 2 diabetes. New research suggests the everyday diabetes drug may be linked to better survival after COVID-19, while experts still urge caution about reading too much into the data.
For years, metformin has been a go-to option for keeping blood sugar in check. Now, a Stanford University analysis points to something more: adults with type 2 diabetes who were taking metformin before getting COVID-19 had a lower risk of dying in the year after infection than people on another diabetes drug.
The study, published in Diabetes, Obesity and Metabolism, looked at more than 53,000 U.S. adults with type 2 diabetes who tested positive for COVID-19 between October 2021 and November 2023. Among them, 50,965 were on metformin and 2,367 were on a DPP-4 inhibitor, a different class of diabetes medication.
Researchers found that the metformin group had a 39% lower risk of death over the following year compared with patients taking the alternative drug. That kind of result turns heads fast, especially because metformin is already one of the most common prescriptions in diabetes care.
The possible explanation goes beyond simple glucose control. High blood sugar can weaken the immune system, and metformin helps the body respond to insulin more effectively, but the researchers also pointed to a biological pathway tied to blood pressure and fluid balance that may play a role in COVID-19 severity.
There are also hints from earlier studies that metformin may calm inflammation and reduce viral levels during active infection. Those ideas are interesting, but they do not automatically prove the drug was the reason for the better outcomes seen in this latest analysis.
Ziyad Al-Aly, M.D., a senior clinical epidemiologist at Washington University in St. Louis who was not part of the research, noted that the comparison is not exactly apples to apples. He explained that metformin is usually the first medication prescribed for type 2 diabetes, while DPP-4 inhibitors often go to older patients or people with kidney disease or other health issues.
“Metformin is the first drug most people with type 2 diabetes are given. DPP-4 inhibitors usually come later, or go to people who cannot take metformin, often because they are older or have kidney disease or other health problems,” Ziyad Al-Aly, M.D., a senior clinical epidemiologist at Washington University in St. Louis, told Fox News Digital.
“Put simply, people on metformin are generally healthier than people on DPP-4 inhibitors,” added Al-Aly, who was not involved in the study.
That matters because the metformin group was a bit younger on average, 60 versus 64, and healthier patients often fare better regardless of the drug they take. The researchers adjusted for age, sex and other variables, but observational studies can only go so far when it comes to separating medication effects from overall health differences.
The data also raised an eyebrow on long COVID. At first, metformin users appeared to have a 13% lower rate of long COVID symptoms, but the signal did not hold up under further statistical testing, so the link was not considered significant.
Even so, the findings line up with other recent work, including research from the University of Minnesota Medical School showing that starting metformin within six days of a COVID-19 diagnosis was tied to a lower risk of death or long COVID. That kind of overlap keeps metformin on researchers’ radar, even if it is not time to call it a miracle drug.
Al-Aly said there may be something worth studying, but he also stressed that bigger randomized trials are still needed. “There is some evidence from the same group that metformin, started early in a COVID infection, may lower the risk of long COVID, [but] that still needs to be confirmed in large, well-designed randomized trials,” he noted.
The Stanford team also made clear that the results do not prove metformin caused the improved survival. Since the study used medical records instead of a clinical trial, factors like age, underlying illness and incomplete vaccination records could all have influenced the outcomes.
That caution is especially important because people taking DPP-4 inhibitors often have more complicated medical profiles. As Al-Aly put it, “This is not enough evidence to change treatment,” and patients should not switch medications based on one study, no matter how attention-grabbing the headline sounds.
“People take a DPP-4 inhibitor because they need it to control their diabetes, usually because metformin was not enough or was not an option for them,” he said. “No doctor is choosing between these two drugs for the same patient. The comparison in this study is not a real choice in any clinic. If you take either drug, do not change it because of this study.”
That leaves metformin in a familiar but newly intriguing place, sitting at the intersection of diabetes care, inflammation research and post-COVID questions. The drug has already earned its reputation in one lane, and scientists are still poking around to see whether it has more to give.
