A newly published study on pioglitazone in inclusion body myositis gives reason for cautious optimism, although the study was small and preliminary. The main goal was not to learn whether pioglitazone is effective in treating IBM, but to see if it could shift important energy-related processes inside IBM muscle in a favorable direction.
Why Researchers Studied Pioglitazone in IBM
Researchers noted that endurance exercise can improve muscle function in IBM, and they argued that this benefit is at least partly related to improved mitochondrial function. Mitochondria are the energy-producing structures inside cells. The investigators speculated that they could stimulate some of these same favorable effects with pioglitazone, an FDA-approved drug used to treat diabetes. Endurance exercise and pioglitazone both activate PGC-1α, a protein that helps regulate mitochondrial function and energy production. Pioglitazone has also been shown in other settings to enhance mitochondrial function and mitochondrial biogenesis, meaning it can help cells build and maintain healthier mitochondria.
The researchers compared muscle biopsy and blood samples from people with IBM and from control participants, looking at chemicals involved in the cell’s metabolic pathways. In the IBM group, samples were taken before and after pioglitazone.
What “Metabolism” Means in This Study
People often use “metabolism” to mean how fast the body burns calories, especially in conversations about weight gain or weight loss. For example, someone who eats a lot without gaining weight may be said to have a “fast metabolism.” In biology, the meaning of metabolism is broader, referring to the chemical processes inside your cells that turn food and fuel into energy, while also supplying the raw materials cells need to maintain and repair themselves.
Cells carry this out through metabolic pathways, which are step-by-step chemical routes. At each step, one substance is converted into another, with enzymes helping the process move efficiently and in the proper sequence.
These pathways connect and branch. Some mainly produce energy, while others divert materials toward building, repair, or other essential tasks. So, when a study says a drug “changes metabolism,” it usually means the drug is changing how efficiently these pathways operate, which pathways the cell depends on, or how well the cell can produce energy and maintain itself.
Key Findings
What the Researchers Found in IBM Muscle Before Treatment
In this study, the initial muscle samples from people with IBM showed specific signs that the cells’ usual energy system was under strain. Some chemicals involved in supplying and processing fuel were lower than normal. At the same time, one chemical from the middle of the cell’s main energy cycle built up, while several later ones tended to be lower. Fuel did not seem to be moving smoothly through the muscle cell’s normal energy-producing system. The muscle also showed signs of extra chemical wear and tear. The paper also ties these abnormalities to disturbed mitochondrial function.
What Changed After Pioglitazone
After pioglitazone, some of these changes moved in the right direction. Chemicals that had been lower than normal increased, and the overall findings suggested that fuel was moving somewhat more normally through the muscle cell’s usual energy-producing system. There were also signs of less chemical wear and tear. However, the study’s main endpoint, which was tied to PGC-1α, a key regulator of mitochondrial function, did not reach conventional statistical significance. The study was small and ended early because of the COVID-19 pandemic, which likely made it harder to detect anything but a fairly large effect.
The drug’s effects were not limited to metabolites. Pioglitazone was also associated with broader changes in gene activity inside muscle. After treatment, genes involved in the TCA cycle, oxidative phosphorylation, PPAR signaling, and AMPK signaling were upregulated. The study also found a shift away from inflammatory pathway activity and toward a more metabolically active state. In other words, pioglitazone appeared to affect not only how muscle cells were processing fuel, but also some of the genetic programs linked to mitochondrial function and inflammation.
Only a few participants showed this more favorable metabolic response, and it seemed most prominent in those with milder disease. Among the participants whose metabolic findings improved, decline also appeared to be slower on measures of physical function, such as the IBM Functional Rating Scale.
What Is Pioglitazone?
Pioglitazone, an oral medication, was approved by the FDA in 1999 for the treatment of diabetes. Originally sold under the brand name Actos, it is now available as an inexpensive generic medication. Rather than directly lowering blood sugar, it works by increasing sensitivity to the body’s existing insulin, and it therefore generally lowers blood sugar only when levels are elevated. People who do not have diabetes can take it without significant risk of low blood sugar.
Pioglitazone was once used much more commonly in diabetes care, but its use has declined with the arrival of newer drugs and because of important side effects. These include weight gain, fluid retention, worsening heart failure, and increased bone fracture risk.
Should People With IBM Ask About Pioglitazone Now?
Many readers will naturally wonder whether pioglitazone is something they should ask their doctor about now. That is understandable, especially because IBM is progressive and there are still no established drug treatments. But this was a small preliminary study, and it did not show a clear overall clinical benefit. Its main goal was not to prove that pioglitazone improves strength or daily function in IBM, and the primary metabolic endpoint was not met. Pioglitazone is also not a risk-free drug. For that reason, this study should not be taken as a general recommendation that people with IBM should start asking for pioglitazone prescriptions. Any off-label use would require a careful discussion with a physician who understands the person’s overall medical situation.
What This Study Really Means
Overall, this study was too small and too short to show whether pioglitazone can help people with IBM. But it does suggest that some of the abnormal changes inside IBM muscle may be open to treatment. It also points to effects beyond metabolism alone, including possible effects on mitochondrial function, gene activity, and inflammation inside muscle. That does not make pioglitazone an established therapy, but it does make this general treatment strategy worthy of attention.
Published study: “Modifying muscle metabolic dysregulation in inclusion body myositis with pioglitazone: a single-arm trial.” A PDF of the full article is available for download.
Learn more: Medications for inclusion body myositis
Learn more: Clinical trials for inclusion body myositis
by Kevin Dooley, MD
March 18, 2026