Xigduo XR is a once-daily fixed-dose oral tablet combining dapagliflozin (an SGLT2 inhibitor) with extended-release metformin (a biguanide) for adults with type 2 diabetes. It delivers combined A1C reduction of approximately 1.5 to 2.5 percent, modest weight loss, blood pressure reduction, and the cardiovascular and kidney benefits demonstrated by dapagliflozin in the DAPA-HF and DAPA-CKD trials.
What Xigduo XR Contains
Xigduo XR is manufactured by AstraZeneca. Each tablet contains two active ingredients:
- Dapagliflozin — an SGLT2 inhibitor that blocks glucose reabsorption in the proximal tubule of the kidney, allowing approximately 50 to 80 grams of excess glucose to be excreted in urine daily. It lowers blood sugar independently of insulin and provides weight loss, blood pressure reduction, and cardiovascular and kidney protection.
- Metformin hydrochloride extended-release — a biguanide that decreases hepatic glucose production, modestly improves insulin sensitivity in peripheral tissues, and slows intestinal glucose absorption. The extended-release formulation reduces gastrointestinal side effects compared with immediate-release metformin.
Because the two drugs work through different mechanisms — renal glucose excretion and hepatic glucose suppression — their effects add together for greater glucose lowering than either alone.
Available Strengths
| Strength | Dapagliflozin | Metformin XR | Typical Patient |
|---|---|---|---|
| 5/500 mg | 5 mg | 500 mg | Starting strength, metformin-naive |
| 5/1000 mg | 5 mg | 1,000 mg | Adequate dapagliflozin, higher metformin need |
| 10/500 mg | 10 mg | 500 mg | Need maximum SGLT2 effect, low metformin tolerance |
| 10/1000 mg | 10 mg | 1,000 mg | Maximum daily dose |
Maximum daily dose is dapagliflozin 10 mg plus metformin XR 2,000 mg, achieved by taking two of the 5/1000 mg tablets together with the evening meal, or one 10/1000 mg tablet plus an additional 1,000 mg metformin XR with another meal.
Dosing Instructions
- Take once daily with the evening meal to minimize GI side effects.
- Swallow whole — do not crush, split, or chew (the metformin XR matrix must remain intact).
- If a dose is missed, take it with food as soon as remembered the same day. Skip if it is close to the next scheduled dose.
- Maintain adequate hydration throughout the day.
Who Xigduo XR Is For
Xigduo XR is approved for adults with type 2 diabetes as an adjunct to diet and exercise. Common scenarios:
- A1C remains above goal on metformin monotherapy
- Already taking dapagliflozin and metformin separately and want to consolidate
- Heart failure with reduced or preserved ejection fraction (DAPA-HF benefit)
- Chronic kidney disease (DAPA-CKD benefit)
- Cardiovascular disease or elevated risk
- Desire for weight loss alongside glycemic control
It is not approved for type 1 diabetes, diabetic ketoacidosis, or pediatric patients.
How Well Xigduo XR Works
Clinical data from the component drugs and combination studies show:
- A1C reduction: approximately 1.5 to 2.5 percent in patients with poorly controlled type 2 diabetes.
- Weight loss: 2 to 4 kg over 24 to 52 weeks, primarily from the dapagliflozin component.
- Blood pressure: systolic reduction of 3 to 5 mmHg.
- Heart failure: DAPA-HF showed dapagliflozin reduced cardiovascular death or heart failure hospitalization by 26 percent in patients with heart failure with reduced ejection fraction, regardless of diabetes status. DELIVER trial showed similar benefit in heart failure with preserved ejection fraction.
- Kidney protection: DAPA-CKD trial showed a 39 percent reduction in kidney disease progression or death in chronic kidney disease patients, regardless of diabetes status.
For context on what these A1C reductions mean clinically, see our guide on A1C levels and treatment targets.
Side Effects
| Side Effect | Source | Approximate Frequency |
|---|---|---|
| Genital yeast infections | Dapagliflozin | 4 to 12 percent (higher in women) |
| Urinary tract infections | Dapagliflozin | 5 to 8 percent |
| Increased urination, thirst | Dapagliflozin | 3 to 5 percent |
| Nausea, diarrhea, abdominal discomfort | Metformin XR | 5 to 15 percent (often improves with time) |
| Metallic taste | Metformin | 3 percent |
| Vitamin B12 deficiency | Metformin (long-term use) | 5 to 10 percent at 5+ years |
| Dehydration, hypotension | Dapagliflozin | 1 to 3 percent |
| Euglycemic DKA | Dapagliflozin | Rare (less than 0.1 percent) |
| Lactic acidosis | Metformin | Very rare (3 to 10 per 100,000) |
| Acute kidney injury | Both | Rare |
| Fournier’s gangrene (perineal necrotizing fasciitis) | SGLT2 class | Extremely rare |
Contraindications and Warnings
- eGFR less than 30 mL/min/1.73 m squared: contraindicated due to metformin lactic acidosis risk.
- eGFR 30 to 45: existing users may continue cautiously; do not initiate.
- Active diabetic ketoacidosis: contraindicated.
- Severe hepatic impairment, acute or chronic metabolic acidosis, or chronic alcoholism: increase lactic acidosis risk.
- History of recurrent urinary or genital infections: use cautiously.
- Iodinated contrast imaging: hold Xigduo XR 48 hours before and after.
- Surgery and prolonged fasting: hold for 3 to 4 days perioperatively.
- Pregnancy: not recommended in second or third trimester.
Drug Interactions
- Loop and thiazide diuretics: additive volume depletion — monitor blood pressure and renal function.
- Insulin and sulfonylureas: increase hypoglycemia risk; dose reductions may be needed.
- Cationic drugs (cimetidine, dolutegravir, ranolazine): can elevate metformin levels.
- Iodinated contrast: see above.
- Alcohol: increases lactic acidosis and hypoglycemia risk.
- Lithium: SGLT2 inhibitors can alter lithium clearance.
Cost and Insurance
Xigduo XR typically retails for $550 to $700 per month without insurance. AstraZeneca offers a manufacturer savings card that reduces eligible commercially insured patients’ copays to as little as $0 to $20 per month, with annual maximums. Medicare and Medicaid patients are not eligible for the savings card but may qualify for AstraZeneca’s patient assistance program based on income. Some patients find the regimen cheaper by taking generic metformin XR (about $15 per month) plus brand Farxiga separately, especially if Farxiga has lower copays on their formulary than Xigduo XR.
Storage
- Store at controlled room temperature 68 to 77 degrees F.
- Keep in original blister or bottle until use.
- Protect from moisture and heat.
- Do not crush, split, or chew tablets.
Xigduo XR vs Components Taken Separately
| Approach | Daily Pills | Approx Cost (no insurance) | Convenience |
|---|---|---|---|
| Xigduo XR (one tablet) | 1 pill once daily | $550 to $700 | Highest |
| Farxiga + generic metformin XR (separate) | 2 pills daily | $550 to $620 | Lower (2 bottles) |
| Generic metformin alone | 1 to 2 pills daily | $10 to $25 | Highest cost-efficiency |
Combining into Xigduo XR is convenient but rarely cheaper than separate components, because generic metformin is inexpensive while brand dapagliflozin makes up most of the cost either way.
Xigduo XR vs Synjardy and Invokamet
All three combine an SGLT2 inhibitor with metformin and are largely interchangeable from a pharmacologic standpoint. Synjardy uses empagliflozin and has the EMPA-REG cardiovascular outcome data. Invokamet uses canagliflozin and has the CANVAS and CREDENCE data, but is less prescribed due to historical amputation and fracture signals. Xigduo XR uses dapagliflozin with strong heart failure and kidney disease evidence. The choice often depends on insurance formulary preference more than clinical differences.
Place in Modern Type 2 Diabetes Care
ADA Standards of Care 2024 recommend SGLT2 inhibitors as preferred second-line agents for patients with type 2 diabetes plus atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease — regardless of A1C. Adding metformin (or continuing it) is also recommended for most patients. Xigduo XR delivers both in one tablet, simplifying adherence. For an overview of where SGLT2 inhibitors fit, see our treatment options page.
Practical Tips
- Drink at least 8 glasses of water daily — dehydration is the most common preventable side effect.
- Practice good genital hygiene; uncircumcised men should clean the foreskin daily to reduce yeast infection risk.
- Inform any clinician about Xigduo XR before scheduled surgery or contrast imaging.
- Monitor for ketoacidosis signs (severe nausea, vomiting, fruity breath, rapid breathing, abdominal pain) even when blood sugar is normal — this is the unusual presentation of euglycemic DKA.
- Check kidney function (eGFR) at least annually and after any acute illness.
- Stop and seek emergency care for any sudden severe pain, swelling, or discoloration in the genital or perineal area — Fournier’s gangrene is extremely rare but emergent.
Xigduo XR and Weight Loss
Patients can expect to lose 2 to 4 kg (4 to 9 pounds) over the first 6 to 12 months, primarily from the dapagliflozin component’s caloric losses through urinary glucose excretion. Weight loss tends to plateau after a year. For larger weight loss, GLP-1 receptor agonists like semaglutide or tirzepatide produce greater effects. See our pieces on Wegovy vs Ozempic and Mounjaro vs Ozempic for context on alternative approaches.
The Bottom Line
Xigduo XR combines dapagliflozin and extended-release metformin in a once-daily tablet for adults with type 2 diabetes. Four strengths allow flexible titration, delivering combined A1C reduction of 1.5 to 2.5 percent, modest weight loss, blood pressure reduction, and the heart failure and kidney protection benefits of dapagliflozin demonstrated in DAPA-HF and DAPA-CKD. Common side effects are genital yeast infections, urinary tract infections, and mild gastrointestinal symptoms. It is contraindicated below eGFR 30 and should be held around contrast imaging and surgery. Cost is similar to brand Farxiga alone, and manufacturer copay cards make it accessible for most commercially insured patients. Talk to your clinician about whether Xigduo XR fits your kidney function, cardiovascular risk profile, and adherence preferences.
