Short answer: The Duetact label lists upper respiratory infection, accidental injury and swelling as its most common side effects. In a 24-week trial of pioglitazone with a sulfonylurea, low blood sugar affected 13.4% on 30 mg and 15.7% on 45 mg, weight gain 9.1% and 13.4%, and leg swelling 5.7% and 12.3%. Duetact has a boxed warning for congestive heart failure from its pioglitazone part.
What Duetact is approved for: Duetact combines pioglitazone, a thiazolidinedione, with glimepiride, a sulfonylurea. It is approved, along with diet and exercise, to improve blood sugar control in adults with type 2 diabetes who already take a thiazolidinedione and a sulfonylurea, or whose blood sugar is not controlled on one of them alone (section 1). It is not for type 1 diabetes or diabetic ketoacidosis.
Source
DUETACT (pioglitazone and glimepiride) tablets, for oral use, prescribing information and Medication Guide. Takeda Pharmaceuticals America. DailyMed, version published April 9, 2025. DailyMed setid f8b0c917-3fdd-4a28-a47d-6225b8195458
WARNING: CONGESTIVE HEART FAILURE
Thiazolidinediones, including the pioglitazone in Duetact, cause or worsen congestive heart failure in some people. After starting and after dose increases, people are watched closely for fast weight gain, shortness of breath or swelling, and stopping it or lowering the dose must be considered if heart failure develops. Duetact is not recommended with symptomatic heart failure, and starting it is contraindicated in NYHA Class III or IV heart failure.
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 Duetact.
| Adverse Event | Pioglitazone 30 mg + Sulfonylurea N=351 n (%) | Pioglitazone 45 mg + Sulfonylurea N=351 n (%) |
|---|---|---|
| Hypoglycemia | 47 (13.4) | 55 (15.7) |
| Upper Respiratory Tract Infection | 43 (12.3) | 52 (14.8) |
| Weight Increased | 32 (9.1) | 47 (13.4) |
| Edema Lower Limb | 20 (5.7) | 43 (12.3) |
| Headache | 25 (7.1) | 14 (4.0) |
| Urinary Tract Infection | 20 (5.7) | 24 (6.8) |
| Diarrhea | 21 (6.0) | 15 (4.3) |
| Nausea | 18 (5.1) | 14 (4.0) |
| Pain in Limb | 19 (5.4) | 14 (4.0) |
Number of patients with the percent in brackets. Pioglitazone was given with a sulfonylurea; there was no placebo group. Study stopping for side effects was 6% on 30 mg and 9.7% on 45 mg.
| Adverse event | Placebo N=2633 | Pioglitazone 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 |
% of patients; mean follow-up 34.5 months in people with type 2 diabetes and blood vessel disease.
| Group | Placebo | Pioglitazone 15 mg | Pioglitazone 30 mg | Pioglitazone 45 mg |
|---|---|---|---|---|
| Combined Therapy (16 to 24 weeks): Sulfonylurea | 4 (2.1%) N=187 | 3 (1.6%) N=184 | 61 (11.3%) N=540 | 81 (23.1%) N=351 |
Number of patients (%). Edema combines leg swelling, general swelling, pitting swelling and fluid retention. Only the sulfonylurea row of the table is shown.
In 16-week trials of pioglitazone 15 mg and 30 mg added to a sulfonylurea vs placebo plus a sulfonylurea: upper respiratory infection 16.6% vs 15.5%, accidental injury 3.5% vs 8.6%, and swelling 7.2% vs 2.1%.
Pioglitazone alone vs placebo (Table 2): upper respiratory infection 13.2% vs 8.5%, headache 9.1% vs 6.9%, sinusitis 6.3% vs 4.6%, muscle pain 5.4% vs 2.7%, and sore throat 5.1% vs 0.8%.
Heart failure with pioglitazone added to a sulfonylurea (Table 4): 1.7% on 45 mg and 0.3% on 30 mg over 24 weeks; none were fatal. In people who already had NYHA Class II or early Class III heart failure, overnight hospital stays for worse heart failure were 9.9% on pioglitazone vs 4.7% on glyburide.
Low blood sugar with pioglitazone added to a sulfonylurea: 3.7% on 30 mg vs 0.5% on placebo over 16 weeks. Glimepiride alone: possible low blood sugar 19.7% vs 3.2% on placebo over 22 weeks.
Glimepiride alone vs placebo, other than low blood sugar: headache 8.2% vs 7.8%, accidental injury 5.8% vs 3.4%, flu syndrome 5.4% vs 4.4%, nausea 5.0% vs 3.4%, and dizziness 5.0% vs 2.4%. Allergic skin reactions occurred in less than 1%.
Weight change with pioglitazone plus a sulfonylurea over 16 to 24 weeks (Table 8): a median gain of 2.0 kg on 15 mg, 3.1 kg on 30 mg and 4.1 kg on 45 mg, vs a 0.5 kg loss on placebo.
Reported after approval: worse diabetic macular edema, fatal and nonfatal liver failure, heart failure and unusually fast weight gain with pioglitazone; and with glimepiride, serious allergic reactions, hemolytic anemia, liver problems, sun sensitivity, low blood counts, porphyria reactions, disulfiram-like reactions and low sodium.
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. The boxed-warning risk. Pioglitazone can cause dose-related fluid retention, most often with insulin, which can cause or worsen heart failure. People are watched for symptoms, and stopping or lowering the dose of Duetact must be considered if heart failure develops.
Hypoglycemia. Glimepiride, like all sulfonylureas, can cause severe low blood sugar, which can lead to unconsciousness, seizures, temporary or permanent harm to brain function, or death and can affect driving. Risk is higher in older people, with kidney problems, other diabetes medicines, skipped meals, hard exercise or alcohol.
Hypersensitivity reactions. Serious allergic reactions to glimepiride, including anaphylaxis, angioedema and Stevens-Johnson syndrome, have been reported. Duetact is stopped promptly if one is suspected.
Potential increased risk of cardiovascular mortality with sulfonylureas. In an older long-term study, tolbutamide, another sulfonylurea, was linked to heart-related death about 2.5 times that of diet alone. The label applies this warning to the whole class.
Hepatic effects. Fatal and non-fatal liver failure has been reported with pioglitazone after approval. Liver tests are taken before starting and checked promptly if symptoms appear; Duetact is interrupted if ALT is above three times normal.
Urinary bladder tumors. Pioglitazone may be linked to bladder tumors. In PROactive, bladder cancer was 0.54% on pioglitazone vs 0.19% on placebo, though rates did not differ over 13 years of follow-up. Duetact is not used with active bladder cancer.
Edema. Swelling was more frequent on pioglitazone than placebo and is dose-related. Duetact is used with caution in people with swelling or at risk of heart failure.
Fractures. In PROactive, fractures in women were 5.1% on pioglitazone vs 2.5% on placebo, mostly of the lower limb and lower arm, with no increase in men.
Hemolytic anemia. Sulfonylureas can break down red blood cells in people with G6PD deficiency, and this has also been reported with glimepiride in people without it.
Macular edema. Swelling at the back of the eye has been reported with pioglitazone, sometimes with blurred vision. Regular eye exams are advised, and visual symptoms are referred to an eye doctor.
Macrovascular outcomes. No study has shown that Duetact lowers the risk of heart attack, stroke or other large blood vessel disease.
From the Medication Guide that comes with Duetact:
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.