Xigduo XR Side Effects: What to Expect and When to Call Your Doctor

Starting any new medication raises questions, and Xigduo XR (dapagliflozin/metformin extended-release) is no different. Understanding what side effects to expect — and which ones require immediate medical attention — can help you use this medication more safely and confidently.

Xigduo XR combines two active ingredients, each with its own side effect profile. Dapagliflozin (an SGLT2 inhibitor) and metformin (a biguanide) both contribute to the overall side effect picture.

Most Common Side Effects of Xigduo XR

In clinical trials, the most common side effects (reported in more than 5% of patients) were:

Female genital mycotic infections (yeast infections): This is a hallmark side effect of SGLT2 inhibitors. Extra sugar in the urine can promote yeast growth in the genital area, especially in women. Good hygiene reduces risk; most cases are treatable with over-the-counter antifungals.

Urinary tract infections (UTIs): Dapagliflozin increases glucose in the urinary tract, which can support bacterial growth. UTIs occur in some patients. Staying well-hydrated and urinating after intercourse may help reduce risk.

Nasopharyngitis (common cold symptoms): Reported in clinical trials; generally mild and resolves on its own.

Diarrhea: Primarily from the metformin component. Usually worst when starting the medication. Taking Xigduo XR with food and starting at lower doses can help reduce GI side effects.

Headache: Common and typically mild; often improves over time.

Increased urination: Dapagliflozin works by making your kidneys excrete excess glucose in urine, which increases urine output. This is expected and is part of how the medication works.

Nausea: Again mostly from metformin; usually worse when starting and improves over 2-4 weeks. Always take with food.

Serious Side Effects: When to Call Your Doctor or Seek Emergency Care

While serious side effects are uncommon, they can be life-threatening. Know these warning signs:

Lactic Acidosis (Boxed Warning)

Lactic acidosis is a rare but serious buildup of lactic acid in the blood, caused by the metformin component. It carries a boxed warning — the FDA's most serious warning. Risk is higher in patients with kidney disease, liver disease, chronic alcoholism, or during severe illness.

Call emergency services or go to the ER immediately if you have: unusual muscle pain, difficulty breathing, stomach pain, dizziness, unusual tiredness, feeling cold or blue, or an irregular heartbeat. Lactic acidosis can be fatal — this is a genuine emergency.

Diabetic Ketoacidosis (DKA)

SGLT2 inhibitors can rarely cause diabetic ketoacidosis even at normal blood sugar levels. Signs include nausea, vomiting, stomach pain, tiredness, or fruity-smelling breath. Seek emergency care immediately. Xigduo XR should be held before major surgery or if you are fasting or very sick.

Serious Urinary Tract Infections

Untreated UTIs can progress to serious kidney infections (pyelonephritis) or blood poisoning (urosepsis). Call your doctor right away if you have fever, back or side pain, burning with urination, or cloudy/bloody urine. Don't wait these out at home.

Dehydration and Low Blood Pressure

Dapagliflozin increases urination, which can lead to dehydration and low blood pressure, especially in elderly patients or those on diuretics. Symptoms include dizziness when standing, lightheadedness, and feeling faint. Stay well-hydrated and contact your doctor if you experience persistent dizziness.

Necrotizing Fasciitis (Fournier's Gangrene)

A very rare but severe genital tissue infection has been reported with SGLT2 inhibitors. Seek emergency care if you have severe pain, swelling, redness, or foul smell in the genital or rectal area, along with fever or feeling very unwell. This is an emergency.

Low Blood Sugar (Hypoglycemia)

Xigduo XR does not typically cause low blood sugar on its own. However, if you are also taking insulin or a sulfonylurea, your risk of hypoglycemia increases. Your doctor may need to lower the dose of your other diabetes medication when you start Xigduo XR.

Vitamin B12 Deficiency

Long-term use of metformin can reduce B12 absorption. Your doctor should check your blood B12 levels annually. Symptoms of B12 deficiency include tingling or numbness in hands/feet, fatigue, and anemia. If low, you may need B12 supplements.

Tips to Minimize Side Effects

Always take Xigduo XR with food in the morning to reduce GI side effects

Swallow tablets whole — do not crush, cut, or chew

Drink plenty of water daily to reduce dehydration and UTI risk

Practice good genital hygiene to reduce yeast infection risk

Avoid excessive alcohol, which increases lactic acidosis risk

Tell your doctor if you're planning surgery — Xigduo XR should be held at least 3 days before major procedures

For a complete list of drug interactions with Xigduo XR, see our guide on Xigduo XR drug interactions: what to avoid and what to tell your doctor.

If you're still looking for Xigduo XR at a pharmacy near you, medfinder can help you locate which pharmacies have it in stock.