Short answer: In pooled placebo-controlled trials of Actos alone, the most common side effects were upper respiratory infection (13.2% vs 8.5% on placebo), headache (9.1% vs 6.9%), sinusitis, muscle pain (5.4% vs 2.7%) and sore throat. Swelling and weight gain rose with dose and were highest with insulin. Actos has a boxed warning: it can cause or worsen congestive heart failure.
What Actos is approved for: Actos is a thiazolidinedione approved, along with diet and exercise, to improve blood sugar control in adults with type 2 diabetes (section 1). It works only when the body still makes insulin, so it is not for type 1 diabetes or diabetic ketoacidosis, and it is not recommended for children (section 8.4).
Source
ACTOS (pioglitazone) tablets, for oral use, prescribing information and Medication Guide. Takeda Pharmaceuticals America. DailyMed, version published April 9, 2025. DailyMed setid d2ddc491-88a9-4063-9150-443b4fa4330c
WARNING: CONGESTIVE HEART FAILURE
Thiazolidinediones, including Actos, cause or worsen congestive heart failure in some patients. After starting Actos and after dose increases, patients are watched carefully for signs of heart failure, such as excessive, rapid weight gain, shortness of breath or swelling. If heart failure develops, it is treated by current standards and stopping or lowering Actos must be considered. Actos is not recommended in people with symptomatic heart failure, and starting it in people with established NYHA Class III or IV heart failure is contraindicated.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Actos.
| Adverse event | Placebo (%) N=259 | ACTOS (%) N=606 |
|---|---|---|
| Upper Respiratory Tract Infection | 8.5 | 13.2 |
| Headache | 6.9 | 9.1 |
| Sinusitis | 4.6 | 6.3 |
| Myalgia | 2.7 | 5.4 |
| Pharyngitis | 0.8 | 5.1 |
None of these were related to the Actos dose, the label says. Myalgia means muscle pain; pharyngitis means sore throat.
| Adverse event | Placebo + Insulin (%) N=187 | ACTOS 15 mg + Insulin (%) N=191 | ACTOS 30 mg + Insulin (%) N=188 |
|---|---|---|---|
| Hypoglycemia | 4.8 | 7.9 | 15.4 |
| Edema | 7.0 | 12.6 | 17.6 |
| Upper Respiratory Tract Infection | 9.6 | 8.4 | 14.9 |
| Headache | 3.2 | 3.1 | 6.9 |
| Weight Increased | 0.5 | 5.2 | 6.4 |
| Back Pain | 4.3 | 2.1 | 5.3 |
| Dizziness | 3.7 | 2.6 | 5.3 |
| Flatulence | 1.6 | 3.7 | 5.3 |
Edema combines peripheral, generalized and pitting edema and fluid retention. The 24-week part of Table 4 (30 mg vs 45 mg, no placebo) is summarized below the tables.
| Adverse event | Placebo (%) N=2633 | ACTOS (%) N=2605 |
|---|---|---|
| Hypoglycemia | 18.8 | 27.3 |
| Edema | 15.3 | 26.7 |
| Cardiac Failure | 6.1 | 8.1 |
| Pain in Extremity | 5.7 | 6.4 |
| Back Pain | 5.1 | 5.5 |
| Chest Pain | 5.0 | 5.1 |
People with type 2 diabetes and past large-vessel disease, Actos force-titrated up to 45 mg daily; mean follow-up 34.5 months.
Swelling (edema) rose with dose: alone, 1.2% on placebo vs 2.5%, 4.7% and 6.5% on 15, 30 and 45 mg; with insulin, 7.0% vs 12.6%, 20.5% and 26.1% (Table 12). In PROactive, 27.3% vs 15.9% (Table 13).
Median weight change alone over 16 to 26 weeks: -1.4 kg on placebo vs +0.9, +1.0 and +2.6 kg on 15, 30 and 45 mg. With insulin, +2.3 to +4.1 kg. In PROactive, +3.6 kg vs -0.5 kg (Tables 10 and 11).
Hospitalized heart failure in PROactive: 5.7% on Actos vs 4.1% on placebo; fatal 1.0% vs 0.8% (Table 8). In people with NYHA Class II or III heart failure, overnight hospital stays for worse heart failure were 9.9% on Actos vs 4.7% on glyburide (Table 7).
Bone fractures in women in PROactive: 5.1% on Actos vs 2.5% on placebo, mostly of the lower limb and lower arm. No increase in men (1.7% vs 2.1%).
Bladder cancer in PROactive: 0.54% on Actos vs 0.19% on placebo. Over 13 years of trial plus follow-up, rates did not differ (HR 1.00). Observational studies disagree.
Mean hemoglobin fell 2% to 4% on Actos vs -1% to +1% on placebo, mostly in the first 4 to 12 weeks. CPK rose above 10 times normal in 0.2%.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Congestive heart failure. Actos can cause dose-related fluid retention, most often with insulin, which can lead to or worsen heart failure. People are watched for signs, and stopping or lowering Actos is considered if heart failure develops.
Low blood sugar. With insulin or other diabetes medicines, especially sulfonylureas, low blood sugar can occur, and the dose of the other medicine may need to be lowered.
Liver effects. Fatal and non-fatal liver failure has been reported after approval. Liver tests are done before starting. If ALT is over 3 times normal, Actos is paused; with ALT over 3 times and bilirubin over 2 times normal and no other cause, it is not restarted.
Bladder tumors. Actos may be linked to a higher risk of bladder tumors. It is not used in active bladder cancer, and benefits and unknown risks are weighed in people with past bladder cancer.
Swelling. Edema was more common than on placebo and dose-related. Actos is used with caution in people with edema or at risk of heart failure.
Fractures. More bone fractures were seen in women on Actos, starting after the first year. The label says fracture risk is considered, especially in women, and bone health is assessed.
Macular edema. Swelling in the back of the eye has been reported, sometimes with blurred or reduced vision. Some people improved after stopping. Regular eye exams are part of diabetes care.
Unplanned pregnancy. Actos may cause ovulation in some premenopausal women who do not ovulate, which can lead to an unintended pregnancy.
From the Medication Guide that comes with Actos:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.