Why Actos May Be Reemerging in the Diabetes Landscape
By: Beverly Thomassian
In the ever-evolving world of diabetes care, medications come in and out of favor based on new research, shifting safety data, and patient needs. Actos (pioglitazone), once a go-to medication for improving insulin sensitivity, fell out of favor due to concerns about side effects. Now, it’s gaining renewed interest—especially in specific populations who may benefit from its unique profile.
What is Actos?
Actos is part of the thiazolidinedione (TZD) class of medications that work by enhancing insulin sensitivity, primarily through activation of PPAR-γ receptors in adipose and muscle tissue. It was widely used in the early 2000s before being overshadowed by newer classes like GLP-1 receptor agonists and SGLT2 inhibitors.
Why the Renewed Interest?
1. Cardiovascular and Metabolic Benefits
The IRIS trial demonstrated that pioglitazone reduced the risk of stroke and myocardial infarction in insulin-resistant patients with a history of cerebrovascular events (Kernan et al., 2016). This benefit is being re-evaluated in the context of cardiometabolic risk, especially in patients with atherosclerotic disease or metabolic syndrome.
2. Role in NAFLD and NASH
Pioglitazone has shown promise in improving liver histology in patients with non-alcoholic steatohepatitis (NASH), making it one of the few medications with such benefits (Cusi et al., 2016). It improves hepatic insulin sensitivity, reduces liver fat, and may slow fibrosis progression.
3. Potent Insulin Sensitization
Compared to other oral agents, pioglitazone remains one of the most effective insulin sensitizers, especially useful in patients with significant insulin resistance, such as those with central obesity or polycystic ovary syndrome (PCOS).
4. Re-Evaluating Safety Concerns
Initial concerns about bladder cancer risk stemmed from observational studies, but more recent analyses suggest the risk is low or not statistically significant (Lewis et al., 2015). Furthermore, thoughtful prescribing—avoiding use in patients with heart failure or active bladder cancer risk—helps mitigate potential harm.
Comparative Benefits of Diabetes Medications
Here is a visual summary comparing relative effects of Actos versus other common medications:
Clinical Considerations
When considering Actos, providers should carefully assess:
- Cardiovascular history (benefit in atherosclerosis; caution in heart failure)
- Weight profile (tends to cause weight gain and fluid retention)
- Bladder cancer history
- Liver function and history of NAFLD/NASH
Pioglitazone may also be especially helpful in combination with agents like metformin or GLP-1 receptor agonists, balancing out each other’s side effects and mechanisms of action.
Conclusion
Actos may never regain its former status as a front-line diabetes treatment, but it has a clear and valuable role in today’s therapeutic landscape. For select patients—especially those with insulin resistance, cardiovascular risk, or fatty liver disease—pioglitazone offers an underutilized tool backed by strong evidence and decades of experience.
In diabetes care, what’s old can be new again—especially when paired with clinical wisdom and patient-centered decision-making.
📚 References
- Kernan WN, et al. (2016). Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. NEJM. https://www.nejm.org/doi/full/10.1056/NEJMoa1506930
- Cusi K, et al. (2016). Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes. Ann Intern Med. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327223/
Lewis JD, et al. (2015). Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes. JAMA. https://jamanetwork.com/journals/jama/fullarticle/2281735
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