Duetact

Duetact is a prescription medication used to treat Type 2 Diabetes. It is used in combination with diet and exercise. It is available as a single product containing 2 medications—pioglitazone and glimepiride. 

Pioglitazone belongs to a class of drugs called thiazolidinediones. It helps the body control blood sugar levels by making the body more sensitive to insulin. Glimepiride is in a different class of drugs called sulfonylureas. It causes the pancreas to make more insulin and helps the body to use insulin more efficiently. This helps to control blood sugar. 

Duetact is available as a tablet and is taken once daily, with the first meal of the day.

Common side effects of Duetact include hypoglycemia, upper respiratory tract infection, increased weight, and lower limb swelling. 

Duetact may cause low blood sugar, also known as hypoglycemia. This can reduce your ability to concentrate or react. Do not drive or operate heavy machinery until you know how Duetact affects you, or if you are having any signs or symptoms of hypoglycemia.

Serious side effects have been reported with Duetact. See the Duetact "Precautions" section for more information.

Common side effects of Duetact include the following:

• Low blood sugar
• Infection of the upper airways
• Weight increase
• Swelling of the lower limbs
• Headache
• Urinary tract infection
• Diarrhea
• Nausea

This is not a complete list of Duetact side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Duetact, there are no specific foods that you must exclude from your diet when receiving this medication.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. A glimepiride and pioglitazone overdose can cause life-threatening hypoglycemia. Symptoms of severe hypoglycemia include extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, and seizure (convulsions).

In the U.S.

• Duetact

Available Dosage Forms:

• Tablet

Therapeutic Class: Antidiabetic

Chemical Class: 2nd Generation Sulfonylurea

• It is used to lower blood sugar in patients with high blood sugar (diabetes).

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Change in eyesight.
• Pain when passing urine or blood in urine.
• Passing urine more often.
• Bone pain.
• Trouble swallowing.
• Feeling very tired or weak.
• Very bad dizziness or passing out.
• A fast heartbeat.
• A heartbeat that does not feel normal.
• Period (menstrual) changes.
• Low blood sugar may occur. Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call the doctor right away if any of these signs occur. Follow what you have been told to do if low blood sugar occurs. This may include taking glucose tablets, liquid glucose, or some fruit juices.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• Very bad and sometimes deadly liver problems have happened with Duetact (pioglitazone and glimepiride). Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Recommendations for All Patients

Duetact should be taken once daily with the first main meal.

Duetact tablets are available as a 30 mg pioglitazone plus 2 mg glimepiride or a 30 mg pioglitazone plus 4 mg glimepiride tablet. If therapy with a combination tablet containing pioglitazone and glimepiride is considered appropriate the recommended starting dose is:

• 30 mg/2 mg or 30 mg/4 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability, • for patients inadequately controlled on glimepiride monotherapy: 30 mg/2 mg or 30 mg/4 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability, • for patients inadequately controlled on pioglitazone monotherapy: 30 mg/2 mg once daily and gradually titrated, as needed, after assessing adequacy of therapeutic response and tolerability, • for patients who are changing from combination therapy of pioglitazone plus glimepiride as separate tablets: Duetact should be taken at doses that are as close as possible to the dose of pioglitazone and glimepiride already being taken, • for patients currently on a different sulfonylurea monotherapy or switching from combination therapy of pioglitazone plus a different sulfonylurea (e.g., glyburide, glipizide, chlorpropamide, tolbutamide, acetohexamide): 30 mg/2 mg once daily and adjusted after assessing adequacy of therapeutic response. Observe for hypoglycemia for one to two weeks due to the potential overlapping drug effect. • for patients with systolic dysfunction, the lowest approved dose of Duetact should be prescribed only after titration from 15 mg to 30 mg of pioglitazone has been safely tolerated.

After initiation of Duetact or with dose increase, monitor patients carefully for hypoglycemia and adverse reactions related to fluid retention such as weight gain, edema, and signs and symptoms of congestive heart failure [see Boxed Warning and Warnings and Precautions (5.7)].

Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating Duetact. Routine periodic monitoring of liver tests during treatment with Duetact is not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of Duetact or who are found to have abnormal liver tests while taking Duetact should be managed as described under Warnings and Precautions [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)].

Concomitant Use with an Insulin Secretagogue or Insulin

If hypoglycemia occurs in a patient coadministered Duetact and an insulin secretagogue, the dose of the insulin secretagogue should be reduced.

If hypoglycemia occurs in a patient coadministered Duetact and insulin, the dose of insulin should be decreased by 10% to 25%. Further adjustments to the insulin dose should be individualized based on glycemic response.

Concomitant Use with Strong CYP2C8 Inhibitors

Coadministration of pioglitazone and gemfibrozil, a strong CYP2C8 inhibitor, increases pioglitazone exposure approximately 3-fold. Therefore, the maximum recommended dose of pioglitazone is 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors. If gemfibrozil or other CYP2C8 inhibitors need to co-administered, patients should switch to individual components of Duetact because the minimum dose of pioglitazone in Duetact exceeds 15 mg [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Concomitant Use with Colesevelam

When colesevelam is coadministered with glimepiride, maximum plasma concentration and total exposure to glimepiride is reduced. Therefore, Duetact should be administered at least four hours prior to colesevelam [see Drug Interactions (7.6) and Clinical Pharmacology (12.3)].

There have been no clinical efficacy studies conducted with Duetact. However, the efficacy and safety of the separate components have been previously established. The coadministration of pioglitazone and a sulfonylurea, including glimepiride, has been evaluated for efficacy and safety in two clinical studies. These clinical studies established an added benefit of pioglitazone in glycemic control of patients with inadequately controlled type 2 diabetes while on sulfonylurea therapy. Bioequivalence of Duetact with coadministered pioglitazone and glimepiride tablets was demonstrated at the 30 mg/2 mg and 30 mg/4 mg dosage strengths [see Clinical Pharmacology (12.3)].

Two clinical trials were conducted with pioglitazone in combination with a sulfonylurea. Both studies included patients with type 2 diabetes on any dose of a sulfonylurea, either alone or in combination with another antidiabetic agent. All other antidiabetic agents were withdrawn at least three weeks prior to starting study treatment.

In the first study, 560 patients were randomized to receive 15 mg or 30 mg of pioglitazone or placebo once daily for 16 weeks in addition to their current sulfonylurea regimen. Treatment with pioglitazone as add-on to sulfonylurea produced statistically significant improvements in HbA1c and FGP at endpoint compared to placebo add-on to sulfonylurea (Table 15).

Table 15. Glycemic Parameters in a 16-Week Placebo-Controlled, Add-on to Sulfonylurea Trial
	Placebo + Sulfonylurea	Pioglitazone 15 mg + Sulfonylurea	Pioglitazone 30 mg + Sulfonylurea
Total Population
HbA1c (%)	N=181	N=176	N=182
Baseline (mean)	9.9	10.0	9.9
Change from baseline (adjusted mean*)	0.1	-0.8	-1.2
Difference from placebo + sulfonylurea (adjusted mean*) 95% Confidence Interval		-0.9† (-1.2, -0.6)	-1.3† (-1.6, -1.0)
Fasting Plasma Glucose (mg/dL)	N=182	N=179	N=186
Baseline (mean)	236	247	239
Change from baseline (adjusted mean*)	6	-34	-52
Difference from placebo + sulfonylurea (adjusted mean*) 95% Confidence Interval		-39† (-52, -27)	-58† (-70, -46)
*Adjusted for baseline, pooled center, and pooled center by treatment interaction †p ≤0.05 versus placebo + sulfonylurea

In the second trial, 702 patients were randomized to receive 30 mg or 45 mg of pioglitazone once daily for 24 weeks in addition to their current sulfonylurea regimen. The mean reduction from baseline at Week 24 in HbA1c was 1.6% for the 30 mg dose and 1.7% for the 45 mg dose (see Table 16). The mean reduction from baseline at Week 24 in FPG was 52 mg/dL for the 30 mg dose and 56 mg/dL for the 45 mg dose.

The therapeutic effect of pioglitazone in combination with sulfonylurea was observed in patients regardless of the sulfonylurea dose.

Table 16. Glycemic Parameters in a 24-Week Add-on to Sulfonylurea Trial
	Pioglitazone 30 mg + Sulfonylurea	Pioglitazone 45 mg + Sulfonylurea
Total Population
HbA1c (%)	N=340	N=332
Baseline (mean)	9.8	9.9
Change from baseline (adjusted mean*)	-1.6	-1.7
Difference from 30 mg daily pioglitazone + sulfonylurea (adjusted mean*) (95% CI)		-0.1 (-0.4, 0.1)
Fasting Plasma Glucose (mg/dL)	N=338	N=329
Baseline (mean)	214	217
Change from baseline (adjusted mean*)	-52	-56
Difference from 30 mg daily pioglitazone + sulfonylurea (adjusted mean*) (95% CI)		-5 (-12, 3)
95% CI = 95% confidence interval *Adjusted for baseline, pooled center, and pooled center by treatment interaction

You should not use Duetact if you are allergic to glimepiride or pioglitazone, or sulfa drugs, or if you have:

• severe or advanced heart failure;

• active bladder cancer; or

• diabetic ketoacidosis (call your doctor for treatment with insulin).

To make sure Duetact is safe for you, tell your doctor if you have:

• congestive heart failure or heart disease;

• fluid retention;

• a history of bladder cancer;

• liver disease;

• kidney disease;

• a genetic enzyme deficiency called glucose-6-phosphate dehydrogenase (G6PD) deficiency;

• eye problems caused by diabetes; or

• a history of heart attack or stroke.

This medication may increase your risk of developing bladder cancer. Talk with your doctor about your specific risk.

Taking Duetact may increase your risk of serious heart problems. However, not treating your diabetes can damage your heart and other organs. Talk to your doctor about the risks and benefits of treating your diabetes with this medicine.

Follow your doctor's instructions about using this medicine if you are pregnant. Blood sugar control is very important during pregnancy, and your dose needs may be different during each trimester of pregnancy.

Some women using Duetact have started having menstrual periods, even after not having a period for a long time due to a medical condition. You may be able to get pregnant if your periods restart. Talk with your doctor about the need for birth control.

Women may be more likely than men to have bone fractures in the upper arm, hand, or foot while taking medicine that contains pioglitazone. Talk with your doctor if you are concerned about this possibility.

It is not known whether glimepiride and pioglitazone passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using Duetact.