Metformin Shows Mixed Results Across Diabetes, Longevity, and Long COVID Studies
Recent studies reveal metformin's varied effects: it may extend lifespan in older women with diabetes by 30 percent, but failed to improve long COVID symptoms when given after infection developed.
The diabetes drug metformin demonstrated divergent outcomes across three recent studies examining its effects on longevity, long COVID treatment, and cellular mechanisms related to metabolic disease.
A study published in the Journal of Gerontology: Medical Sciences found that women with type 2 diabetes who took metformin had a 30 percent lower risk of dying before age 90 compared to those taking sulfonylurea, a different diabetes medication. The research analyzed data from 438 postmenopausal women in a long-term US study, with half taking metformin and half taking sulfonylurea. The average follow-up period was 14 to 15 years.
Metformin has been shown to target multiple pathways of aging and is considered a gerotherapeutic drug able to slow down various aging processes in the body. It has been shown to limit DNA damage and promote gene activity associated with long life. Previous studies have shown that metformin can put the brakes on wear and tear in the brain and even reduce the risk of long COVID.
In contrast, a randomized clinical trial published in Annals of Internal Medicine found that a two-week course of metformin did not meaningfully improve recovery from long COVID symptoms. Researchers from Asan Medical Center and Hallym University Kangnam Sacred Heart Hospital in Seoul randomly assigned 396 adults with persistent symptoms to receive metformin, ursodeoxycholic acid (UDCA), or placebo for two weeks in a double-blind trial conducted at two hospitals in South Korea between July 2024 to January 2025, with follow-up completed in April 2025. After eight weeks, recovery rates and symptom improvements were similar across all three groups.
The trial tested whether short-term treatment with metformin, a common diabetes drug shown to reduce the incidence of long COVID by 41 percent, or UDCA, a liver medication with potential antiviral and immunomodulatory effects, could ease long COVID symptoms months after infection. The findings indicate neither drug helped patients recover faster or more completely than placebo when given after symptoms have already developed.
Separate research at the Fralin Biomedical Research Institute at VTC is investigating how exercise-triggered stress reshapes cellular energy systems and whether those mechanisms could help counter metabolic disease. The research focuses on how the body adjusts to stress caused by physical activity and examines these changes to better understand how exercise affects metabolic disorders such as diabetes.
The research examines AMP-activated protein kinase, or AMPK, a key enzyme that helps regulate how cells manage energy. It influences gene activity and cellular signaling pathways to inform mitochondria when more energy is needed. In 2021, findings published in the Proceedings of the National Academy of Sciences revealed AMPK can be found specifically within the mitochondrial reticulum. This distinct AMPK pool, named mitoAMPK after its location in the cell, may allow the enzyme to transmit clearer signals to mitochondria.
In Type 2 diabetes, cells become resistant to insulin, the hormone responsible for aiding in glucose uptake. This creates a cellular environment in which normal energy-sensing mechanisms become overwhelmed and, ultimately, dysfunctional. Because of excess nutrition, skeletal muscle can become overexposed to glucose and therefore become desensitized to its anabolic effects.
The longevity study noted several caveats: participants weren't randomly assigned to treatments but were following professional advice, there wasn't a placebo group that received no treatment, and the overall sample size wasn't particularly large. However, a key advantage was the long follow-up period after treatment initiation enabled by examination of a cohort with extensive follow-up from midlife to ages 90 and older, which is not feasible in typical randomized controlled trials.
The geroscience hypothesis posits that biological aging is malleable and that slowing biological aging may delay or prevent the onset of multiple age-related diseases and disability. A key goal of geroscience is to identify novel therapeutic and preventive interventions that slow biological aging.