Xigduo XR

Blood Sugar Management

Xigduo XR is primarily used to improve glycemic control in adults with type 2 diabetes. It contains two different medications that work in combination with a healthy diet and regular physical activity to help lower blood sugar levels.

Heart Failure Risk Reduction

This medication is also indicated to reduce the risk of hospitalization for heart failure in adults who have both type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors.

Important Limitations

• Xigduo XR is not used for the treatment of type 1 diabetes.
• It should not be used to treat diabetic ketoacidosis, a serious condition that involves high levels of ketones in the blood or urine.
• It is intended for patients for whom treatment with both dapagliflozin and metformin is appropriate.

How the Ingredients Work

Xigduo XR contains two active medicines, dapagliflozin and metformin, which use different methods to control blood glucose (sugar) levels.

Dapagliflozin

Dapagliflozin belongs to a class of drugs called sodium-glucose cotransporter 2 (SGLT2) inhibitors. It works primarily in the kidneys. Under normal conditions, the kidneys filter sugar out of the blood and then reabsorb it back into the bloodstream. Dapagliflozin blocks this reabsorption process, which allows the kidneys to remove excess sugar from the body through urination.

Metformin

Metformin is a biguanide that helps lower blood sugar in three specific ways:

• Liver production: It decreases the amount of glucose that the liver produces and releases into the blood.
• Intestinal absorption: It lowers the amount of sugar the body absorbs from the food you eat.
• Insulin sensitivity: It helps the body's cells respond more effectively to insulin, the natural hormone that moves sugar from the blood into the cells to be used for energy.

By combining these two mechanisms, Xigduo XR provides a multi-pronged approach to managing blood sugar levels throughout the day.

Common Side Effects

Many people using this medication experience mild side effects. These may include:

• Nausea, vomiting, or diarrhea
• Headache
• Sore throat or runny nose
• Back pain
• Genital yeast infections in both men and women
• Urinary tract infections

Serious Side Effects

While less common, some side effects can be severe. Contact a healthcare provider immediately if you notice symptoms of the following conditions:

• Lactic acidosis: A rare but serious buildup of lactic acid in the blood, which can cause extreme tiredness, muscle pain, trouble breathing, or feeling cold.
• Ketoacidosis: High levels of acids called ketones in the blood or urine, which may cause stomach pain, confusion, nausea, or vomiting.
• Dehydration: Loss of too much body water, which can lead to dizziness, lightheadedness, or fainting, especially when standing up.
• Serious infections: This includes severe urinary tract infections or a rare, life-threatening bacterial infection of the skin under the genital area known as Fournier's gangrene.
• Low blood sugar (hypoglycemia): This is more likely if Xigduo XR is taken with other diabetes medicines like insulin or sulfonylureas.
• Kidney problems: Symptoms may include changes in how often you urinate or swelling in the legs and feet.
• Vitamin B12 deficiency: Long-term use of metformin may lower vitamin B12 levels in the blood.

Lactic Acidosis

Metformin, a component of Xigduo XR, has a boxed warning for lactic acidosis, a rare but serious buildup of lactic acid in the blood. This condition is a medical emergency that can be fatal. The risk is higher in people with kidney impairment, liver disease, or congestive heart failure, and in those who consume excessive alcohol. It may also occur during major surgery or certain radiologic tests using contrast dye.

Ketoacidosis

Dapagliflozin can increase the risk of ketoacidosis, a serious condition where the body produces high levels of blood acids called ketones. This can occur even if blood sugar levels are not high. Symptoms such as nausea, vomiting, abdominal pain, and difficulty breathing require immediate medical evaluation.

Kidney Health and Dehydration

This medication can cause the body to lose water and salt, leading to dehydration. This may result in a sudden drop in blood pressure or acute kidney injury. Healthcare providers typically check kidney function before starting treatment and periodically thereafter. Individuals with existing kidney problems or those taking diuretics may be at increased risk.

Serious Infections

• Genital Infections: Both men and women may develop yeast infections while taking this medication.
• Urinary Tract Infections: There is a risk of severe urinary tract infections, including infections that spread to the kidneys or bloodstream.
• Fournier's Gangrene: A rare but life-threatening bacterial infection of the tissues under the skin in the genital area has been reported with SGLT2 inhibitors like dapagliflozin.

Contraindications and Other Precautions

Xigduo XR should not be used by people with severe kidney disease, end-stage renal disease, or those on dialysis. It is also contraindicated for individuals with metabolic acidosis or diabetic ketoacidosis. Long-term use of metformin may lead to low vitamin B12 levels, which may require monitoring by a healthcare professional.

Pregnancy

The use of Xigduo XR is generally not recommended during the second and third trimesters of pregnancy. This is because one of its active ingredients, dapagliflozin, may affect the development of the baby's kidneys during these stages. If you become pregnant while taking this medication, you should contact your healthcare provider immediately to discuss your treatment plan.

Managing blood sugar levels is essential during pregnancy to prevent complications such as birth defects, pregnancy-induced hypertension, or other risks to both the parent and the baby. Your doctor will determine the best way to control your diabetes during this time, which may involve switching to a different medication, such as insulin.

Breastfeeding

It is generally advised not to breastfeed while taking Xigduo XR. While metformin can pass into breast milk in small amounts, it is not known if dapagliflozin passes into human milk. Animal studies have shown that exposure to dapagliflozin during the period corresponding to human breastfeeding can lead to adverse effects on kidney development in the offspring. To avoid potential risks to the nursing infant, healthcare providers usually recommend either stopping the medication or avoiding breastfeeding while using this drug.

Dosage Forms

Xigduo XR is available in the following form:

• Extended-release oral tablet: This formulation is designed to release the medication slowly into the body over time.

The tablets are film-coated and are intended to be swallowed whole. They should not be crushed, chewed, or broken, as this can damage the extended-release properties of the medication.

FDA Approval and Indications

Xigduo XR is approved by the U.S. Food and Drug Administration (FDA) to improve blood sugar control in adults with type 2 diabetes mellitus, when used in combination with diet and exercise. It is a combination of two medications: dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and metformin hydrochloride, a biguanide. It is not indicated for the treatment of type 1 diabetes or diabetic ketoacidosis.

Boxed Warning

This medication carries a boxed warning for lactic acidosis, a rare but serious metabolic complication that can occur due to metformin accumulation. Lactic acidosis is a medical emergency that requires immediate hospitalization. The risk is increased in patients with kidney impairment, heart failure, or those who consume excessive amounts of alcohol.

Regulatory Safety Communications

The FDA has issued several safety updates and communications regarding the components of Xigduo XR:

• Kidney Function: In 2016, the FDA revised the warnings for metformin-containing products to allow their use in patients with mild to moderate kidney impairment, though they remain contraindicated in patients with severe kidney disease.
• Serious Infections: The FDA has identified potential signals of serious risks, such as necrotizing fasciitis of the perineum (Fournier’s gangrene), associated with the SGLT2 inhibitor class of drugs, which includes dapagliflozin.
• Ketoacidosis: Regulatory reviews have also addressed the risk of ketoacidosis, a serious condition where the body produces high levels of blood acids, which has been reported in patients taking SGLT2 inhibitors.

How Xigduo XR Affects Weight

Xigduo XR contains two active ingredients, dapagliflozin and metformin, both of which are associated with weight changes in patients with type 2 diabetes.

Dapagliflozin and Calorie Loss

Dapagliflozin belongs to a class of drugs called SGLT2 inhibitors. It works by preventing the kidneys from reabsorbing glucose back into the blood. Instead, the excess sugar is removed from the body through urine. Because glucose contains calories, this process results in a loss of calories, which can lead to a decrease in body weight.

Metformin and Weight Management

Metformin is generally considered weight-neutral or may lead to modest weight loss. It works by improving how the body responds to insulin and decreasing the amount of sugar the liver produces. Some people may also experience a slight decrease in appetite while taking metformin.

Important Considerations

• Not a weight-loss drug: Xigduo XR is specifically indicated for the treatment of type 2 diabetes alongside diet and exercise. It is not intended to be used solely for weight management.
• Individual results: The amount of weight lost can vary significantly between individuals and is often influenced by lifestyle factors such as diet and physical activity.
• Side effects: While weight loss is often viewed as a benefit, it is technically a side effect of the medication's primary function of lowering blood sugar.