Xigduo XR
Xigduo XR
Generic Name
Xigduo XR
Mechanism
- Dapagliflozin: Inhibits the sodium‑glucose co‑transporter‑2 in the proximal renal tubule, reducing glucose reabsorption (~180 g/day) and promoting glucosuria.
- Metformin (XR): ↓ hepatic gluconeogenesis, ↑ peripheral glucose uptake, and enhances insulin sensitivity. The extended‑release formulation maintains steady plasma levels, reducing peak‑to‑trough variability.
- Synergy: Simultaneous reduction of hepatic glucose production and increased renal glucose excretion leads to additive HbA1c lowering with a lower risk of hypoglycemia compared to insulin or sulfonylureas alone.
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Pharmacokinetics
| Parameter | Dapagliflozin | Metformin (XR) |
| Absorption | Quick, ~70 % bioavailability; peak at ~2 h post‑dose | Gradual release, peak 4–6 h after dosing |
| Half‑life | 13–16 h | 4–8 h (steady state) |
| Metabolism | Minimal CYP; mainly excreted unchanged | No significant metabolism; primarily renal excretion |
| Renal Clearance | 55–60 % unchanged | 90 % unchanged; requires dose adjustment if CrCl < 30 mL/min |
| Food Effect | Minimal | XR formulation reduces peak concentration; food may modestly delay absorption |
Key point: Both agents are largely renally excreted; adequate renal function is essential for safety and efficacy.
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Indications
- Adults with T2DM inadequately controlled on diet/exercise and an additional oral antidiabetic agent.
- Suitable for patients requiring weight loss or cardiovascular risk reduction.
- Recommended when HbA1c ≤ 10 % and normal renal function (CrCl ≥ 60 mL/min).
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Dosing
| Indication | Initial Dose | Titration | Max Daily Dose | Formulation |
| Metformin component | 500 mg XR BID | +500 mg at 4‑week intervals | 2000 mg total (10/1000 mg XR) | Extended‑release |
| Dapagliflozin component | 5 mg XR QD | +5 mg at 4‑week intervals (if tolerated) | 10 mg XR QD | XR |
• Start with the lowest dose in patients with renal impairment or elderly.
• Take with meals to reduce GI upset.
• Swallow whole; do not crush or break the XR tablet.
• Titrate over 4‑8 weeks based on glycemic response and tolerability.
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Monitoring
| Parameter | Frequency | Rationale |
| HbA1c | Every 3 months | Assess glycemic control |
| Fasting plasma glucose | Monthly for first 3 months | Adjust dose early |
| Renal function (CrCl/eGFR) | Monthly until stable, then every 6 months | Protect kidneys |
| Serum electrolytes (Na⁺, K⁺) | Every 6 months | Detect natriuretic shifts |
| Blood pressure | At each visit | Monitor antihypertensive effect |
| Ketone bodies (urine or blood) | Whenever symptoms of ketoacidosis present | Early detection |
| Weight | Every visit | Track weight loss benefit |
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Clinical Pearls
- Start where you can best control it: Many practitioners initiate metformin XR first; if target HbA1c is not met or weight loss is desired, add dapagliflozin XR.
- Avoid abrupt initiation of SGLT‑2 inhibitors in the elderly or those with chronic heart failure; begin at lower dose and provide volume‑status education.
- Combination therapy is synergistic but not additive for hypoglycemia: The risk remains low unless other insulin‑stimulating drugs are co‑administered.
- Take advantage of XR benefits: Extended‑release mitigates the “bumpy” glucose curve typical of metformin IR, improving tolerability and maintaining satiety‑inducing insulin sensitivity over 24 h.
- Watch out for euglycemic DKA: Educate patients that high ketones can occur even with normal glucose. Prompt evaluation of abdominal pain, nausea, or malaise is essential.
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• Key Takeaway:
*Xigduo XR* offers dual‑mechanism glucose control in a once‑daily pill, with benefits in weight loss and blood pressure, providing a convenient, low‑hypoglycemia risk option for many adults with type 2 diabetes.