- Long COVID or post-COVID-19 condition is the long-term symptoms that can develop after experiencing COVID-19.
- One study found that starting metformin within three months of SARS-CoV-2 infection diagnosis may decrease the risk of long COVID in people who have obesity or overweight.
- Metformin is a medication used to treat high blood sugar levels caused by type 2 diabetes.
Long COVID, also called
A recent study published in Clinical Infectious Diseases explored a possible intervention that could help with the prevention of long COVID. This research focused on adults in the United Kingdom who have obesity or overweight.
The results of the study indicated that participants who started metformin within three months of being diagnosed with the infection had a decreased risk of long COVID.
This study delved deeper into the potentially protective effects of the medication metformin. Previous data suggested that starting metformin within three days of COVID-19 diagnosis helped decrease the risk of long COVID.
For the current study, researchers utilized primary care data from individuals in England via a database called the Clinical Practice Research Datalink Aurum. They also had access to mortality data and “Hospital Episode Statistics secondary care datasets.”
Researchers included adults who have obesity or overweight and experienced a SARS-CoV-2 infection. Overweight or obesity was defined as having a body mass index of twenty-five or higher. They excluded participants who had used metformin in the year before, participants who had contraindications to taking metformin, as well as those who were taking other medications to lower blood sugar in the year before.
Researchers examined how many participants developed long COVID. They defined long COVID by two specific diagnostic codes or as having one or more of twenty-five symptoms noted by the World Health Organization (WHO) three months to one year after COVID-19 diagnosis. However, participants had to not have a previous history of the noted symptoms in the 180 days before infection.
Researchers followed participants up to one year after infection diagnosis. They accounted for covariates, including components like ethnicity, age, and COVID-19 vaccination. They also did subgroup analyses for some participants based on things like age and diabetes status.
Overall, researchers included 624,308 participants, and of these, around 3,000 started taking metformin within three months following a COVID-19 diagnosis. When comparing metformin users to non-metformin users, a greater percentage of non-metformin users developed long COVID compared to metformin users.
Researchers concluded that starting metformin within 90 days of infection diagnosis decreased the risk for developing long COVID by 64%. The results were similar for subgroup analyses.
This research was able to show the potential benefits of metformin in decreasing risk for long COVID, even when it is started later after diagnosis.
Jimmy Johannes, MD, pulmonologist and critical care medicine specialist at MemorialCare Long Beach Medical Center in Long Beach, CA, who was not involved in the study, noted the following regarding the study’s findings:
“This study appears to add to the evidence suggesting that metformin use after COVID-19 infection may help prevent long COVID syndrome. While this possibility still needs to be verified with a randomized controlled trial to specifically answer this question, the potential for metformin to help prevent Long COVID is intriguing. This drug is already widely available with a good safety record.”
Researchers note several strengths of their research. For example, there is less risk for bias since they used a sequential trial emulation framework. But there are limitations to the research as well.
First, one of the codes researchers used to identify long COVID “was introduced for clinical use in October 2021.” Researchers acknowledge that the code doesn’t capture cases of Long COVID that happened before this. Thus, there is a risk that cases of Long COVID were underestimated. However, researchers attempted to mitigate this by using the symptoms from the WHO.
Researchers note that it is challenging to show the result of COVID-19 and what might be caused by other conditions. Future research can investigate this relationship.
People who started taking metformin were more likely to have off-label or on-label reasons for using metformin than participants who did not start taking metformin. The groups had differences in baseline characteristics, although researchers were somewhat able to adjust for this.
While the risk is lower than with some other studies, there is some risk for residual confounding. This study did not take into account the dose and formulation of the metformin that participants were taking.
Since this research focused on people who have obesity or overweight, it is not clear if the benefits apply to people outside this body mass index range. The research was also primarily conducted on white individuals, so it’s unclear if the results would also apply to other ethnic groups.
Due to the nature of the study and available data, it’s possible that researchers missed relevant information and that researchers had to make some assumptions. For example, it’s possible that participants weren’t taking metformin even though they were filling prescriptions for it.
Since researchers included people who didn’t have diabetes, they did not evaluate glycemic status. However, they did do a subgroup analysis among participants with diabetes. While researchers did exclude participants on the antiviral nirmatrelvir, they didn’t account for other antivirals that could possibly decrease risk for long COVID-19. However, researchers note that these antivirals, including nirmatrelvir, aren’t used often in the U.K. and are limited to people with COVID-19 and those “at risk of severe SARS-CoV-2 infection.”
Finally, researchers admit that this study lacked statistical power for some subgroups, which limits the “ability to draw a conclusion from subgroup analysis results.”
This research emphasizes another potential benefit of the medication metformin and suggests another strategy that could help with the prevention of Long COVID in people who have obesity or overweight. Brian Lake, D.O., Endocrinology, Diabetes, and Metabolism, for Lake Endocrinology and Diabetes, PLLC, who was not involved in the study, noted the following to Medical News Today about the study’s findings:
“The data from this observational study were significant with a 64% decrease in PCC [Post-Covid-19 Condition] if metformin was started early. With further study confirming the data, I would expect metformin to be a mainstay of treatment to prevent PCC in patients [who have obesity or overweight and] with or without current treatments available to curtail the virus effects.”
Caution in looking at the results is also likely warranted, Johannes noted the following:
“If metformin reduces the risk of long COVID syndrome, then we have a tool that is already widely available, low-cost, and reasonably safe to reduce the terrible burden of long COVID syndrome. While this is an exciting possibility, many proposed treatments for COVID-19 have failed to live up to their promise when tested with a randomized controlled trial. As such, the findings of this study warrant due caution.”
— Jimmy Johannes, MD
Future research can also explore the reasons for the potential helpfulness of metformin in decreasing risk for long COVID, as it’s unclear what underlying mechanisms are involved. It can also include participants from more diverse groups and examine the possible “causal relationship between metformin use and its efficacy in treating PCC in overweight/obesity individuals.”
