Short answer: In a pool of 8 placebo-controlled trials of dapagliflozin with metformin, the most common side effects were female genital yeast infections (9.3% on 10 mg vs 1.5% on placebo with metformin), stuffy or runny nose (5.2% vs 5.9%) and urinary tract infections (5.5% vs 3.6%). Extended-release metformin alone caused diarrhea in 9.6% vs 2.6%. Xigduo XR has a boxed warning for lactic acidosis from its metformin part.
What Xigduo XR is approved for: Xigduo XR combines dapagliflozin, an SGLT2 inhibitor, with extended-release metformin. Along with diet and exercise it is approved to improve blood sugar control in adults and children 10 years and older with type 2 diabetes (section 1). In adults with type 2 diabetes the dapagliflozin part also lowers the risk of kidney decline and heart events in chronic kidney disease, heart death and heart failure events in heart failure, and heart failure hospital stays in people with heart disease or several heart risk factors. It is not recommended for type 1 diabetes.
Source
XIGDUO XR (dapagliflozin and metformin HCl extended-release) tablets, for oral use, prescribing information and Medication Guide. AstraZeneca. DailyMed, version published August 26, 2026. DailyMed setid ac8a0f7b-9f69-4495-abbc-3a47cd75a859
WARNING: LACTIC ACIDOSIS
Cases of metformin-associated lactic acidosis reported after approval have resulted in death, low body temperature, low blood pressure and slow heart rhythms that resist treatment. It often starts subtly, with only vague symptoms such as feeling unwell, muscle aches, trouble breathing, sleepiness and abdominal pain. It was marked by blood lactate above 5 mmol/L, anion gap acidosis without ketones, a raised lactate to pyruvate ratio, and metformin levels generally above 5 mcg/mL. Risk factors include kidney impairment, certain drugs (for example carbonic anhydrase inhibitors such as topiramate), age 65 or older, a radiology study with contrast, surgery and other procedures, low-oxygen states such as acute heart failure, heavy alcohol use, liver impairment and mitochondrial diseases. If it is suspected, Xigduo XR is stopped immediately and supportive care is started in a hospital; prompt hemodialysis is recommended.
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 Xigduo XR.
| Adverse reaction | Placebo and Metformin HCl (N=1185) | Dapagliflozin 5 mg and Metformin HCl (N=410) | Dapagliflozin 10 mg and Metformin HCl (N=983) |
|---|---|---|---|
| Female genital mycotic infections | 1.5 | 9.4 | 9.3 |
| Nasopharyngitis | 5.9 | 6.3 | 5.2 |
| Urinary tract infections | 3.6 | 6.1 | 5.5 |
| Diarrhea | 5.6 | 5.9 | 4.2 |
| Headache | 2.8 | 5.4 | 3.3 |
| Male genital mycotic infections | 0 | 4.3 | 3.6 |
| Influenza | 2.4 | 4.1 | 2.6 |
| Nausea | 2.0 | 3.9 | 2.6 |
| Back pain | 3.2 | 3.4 | 2.5 |
| Dizziness | 2.2 | 3.2 | 1.8 |
| Cough | 1.9 | 3.2 | 1.4 |
| Constipation | 1.6 | 2.9 | 1.9 |
| Dyslipidemia | 1.4 | 2.7 | 1.5 |
| Pharyngitis | 1.1 | 2.7 | 1.5 |
| Increased urination | 1.4 | 2.4 | 2.6 |
| Discomfort with urination | 1.1 | 2.2 | 1.6 |
Percent of patients in a pool of 8 placebo-controlled trials, mean exposure 23 weeks; everyone took metformin. Female and male genital yeast infection rates use the number of women or men in each group. Nasopharyngitis means a stuffy or runny nose with sore throat.
In placebo-controlled trials of extended-release metformin alone, diarrhea was 9.6% vs 2.6% on placebo and nausea or vomiting 6.5% vs 1.5%. Diarrhea led 0.6% to stop.
In the 8-trial pool, any side effect was reported by 60.3% on dapagliflozin 10 mg with metformin vs 58.2% on placebo with metformin. Stopping for side effects was 4% vs 3.3%.
Fluid-loss side effects such as dehydration or low blood pressure in the 12-trial pool: 0.4% on placebo, 0.6% on 5 mg and 0.8% on 10 mg. In the DECLARE trial: 2.4% vs 2.5%.
Low blood sugar was more frequent when dapagliflozin was added to a sulfonylurea or insulin. Added to metformin for 24 weeks, there were no severe episodes and none below 54 mg/dL in any group.
In the DECLARE trial, diabetic ketoacidosis was reported in 27 of 8,574 people on dapagliflozin and 12 of 8,569 on placebo.
Reported after approval, with frequency unknown: Fournier's gangrene, urosepsis and kidney infection; ketoacidosis; acute kidney injury; rash; and, for metformin, liver injury.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Lactic acidosis. The boxed-warning risk. Xigduo XR is not used with an eGFR below 30, and starting it at 30 to 45 is not recommended. It is stopped around some iodinated contrast scans, paused while food and fluids are restricted, stopped in shock, heart attack, sepsis or acute heart failure with low oxygen, and avoided with liver disease.
Ketoacidosis. Ketoacidosis, which can be fatal, can happen even with blood sugar below 250 mg/dL. It is checked for whatever the blood sugar, and Xigduo XR is stopped if it is suspected. It is not recommended in type 1 diabetes.
Volume depletion. Dapagliflozin can cause fluid loss, low blood pressure and acute kidney injury, especially with kidney problems, in older people, with low blood pressure or with loop diuretics. Fluid status is checked before starting.
Urinary and genital infections, including Fournier's gangrene. Serious urinary infections, kidney infections, genital yeast infections and a rare serious genital-area infection (Fournier's gangrene) have been reported. Pain, redness or swelling in the genital area with fever is checked right away.
Low blood sugar with insulin or a sulfonylurea. Low blood sugar risk rises with insulin or a medicine that makes the body release insulin, so a lower dose of those may be needed.
Vitamin B12 deficiency. Metformin may lower vitamin B12. Blood counts are measured yearly and vitamin B12 every 2 to 3 years.
From the Medication Guide that comes with Xigduo XR:
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.