Glucophage XR
Glucophage XR
Generic Name
Glucophage XR
Mechanism
Glucophage XR (extended‑release metformin) primarily lowers blood glucose by:
• Activating AMP‑activated protein kinase (AMPK) in hepatocytes → ↓ hepatic gluconeogenesis and ↓ hepatic glucose output.
• Increasing insulin‑mediated glucose uptake in skeletal muscle and adipose tissue.
• Modifying intestinal glucose absorption and enhancing peripheral glucose utilization.
• Sparing pancreatic β‑cell function by reducing glucotoxicity.
The extended‑release delivery sustains therapeutic plasma concentrations, minimizes peak‑to‑trough variability, and reduces gastrointestinal (GI) adverse effects compared with immediate‑release formulations.
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Pharmacokinetics
| Parameter | Typical Value | Comments |
| Absorption | ~40 % bioavailability; absorbed in the small intestine, peak plasma ~4‑6 h after dose. | XR formulation releases drug gradually over ~12 h. |
| Distribution | Volume of distribution ~63 L kg⁻¹. | No significant protein binding. |
| Metabolism | None → unchanged. | Lacks hepatic metabolism, making it safer in mild hepatic impairment. |
| Excretion | Renal elimination unchanged (≈100 %), half‑life 4.5–5 h (steady‑state ~10 h). | Clearance directly proportional to GFR; dose adjustments required in renal dysfunction. |
| Drug Interactions | Inhibits organic cation transporter 2 (OCT‑2) → ↑ plasma concentrations of other metformin, cimetidine, trimethoprim. | Avoid concurrent use with drugs that markedly reduce GFR (e.g., NSAIDs, ACE inhibitors). |
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Indications
- Type 2 diabetes mellitus (T2DM) – first‑line or adjunct to diet & exercise.
- Metabolic syndrome – improvement of insulin sensitivity.
- Polycystic ovary syndrome (PCOS) – insulin sensitization, ovulation support (off‑label).
- Weight management in obese T2DM patients – modest caloric reduction.
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Contraindications
| Category | Reason / Precautions |
| Contraindicated | *Renal impairment* (eGFR < 30 ml min⁻¹ 1.73 m²), *severe hepatic disease*, *active alcoholism*, *hypoxia, ischemia,* or conditions predisposing to lactic acidosis. |
| Warnings | *Pregnancy* (Category C – potential risks to fetus in early trimesters); *lactation* (data suggest minimal transfer, but caution advised). |
| Precautions | *Cardiovascular disease* (monitor for lactic acidosis), *renal dysfunction* (monitor eGFR and serum creatinine), *NSAID therapy* (reduce renal clearance), *contrast imaging* (stop 48 h before IV contrast). |
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Dosing
| Situation | Starting Dose | Titration | Max Dose | Comments |
| Normal renal function | 500 mg PO BID with meals | Increase 500 mg BID every 1–2 weeks (if tolerated) | 2000 mg/day (1000 mg BID) | XR may be taken once‑daily if GI tolerated. |
| Mild–moderate renal impairment (eGFR 30–60 ml min⁻¹ 1.73 m²) | 500 mg PO BID | Increment as above, but cap at 1500 mg/day (750 mg BID) | 1500 mg/day | Monitor creatinine every 3 months. |
| Patients 65 + (renal screening) | 500 mg PO BID | Same titration | As above | Initiate low dose and titrate slowly. |
| Renal failure or lactic acidosis risk | Hold | – | – | Reinitiate only after eGFR > 45 ml min⁻¹ 1.73 m². |
Take with food to diminish GI irritation. Avoid alcohol to reduce lactic‑acid risk.
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Monitoring
- Blood glucose/HbA1c every 4–12 weeks until stable.
- Renal function (serum creatinine, eGFR) at baseline, every 3 months for the first year, then every 6 months.
- Liver enzymes annually if hepatic disease suspected.
- Vitamin B12 yearly (especially > 2 years therapy).
- Signs of lactic acidosis – dyspnea, fatigue, abdominal pain, hypotension (patient education).
- Weight – monitor for weight loss or gain.
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Clinical Pearls
1. XR for GI tolerance: Extended‑release formulation reduces peak drug exposure, markedly lowering nausea and diarrhea relative to immediate release.
2. Once‑daily dosing possible: If the patient tolerates a 1000 mg dose, consider a single 1000 mg XR dose nightly to improve adherence.
3. Stop before contrast studies: Discontinue ≥48 h before IV contrast‑enhanced imaging to avoid contrast‑induced nephropathy.
4. Renal adjustment algorithm: Use eGFR ≥ 45 ml min⁻¹ 1.73 m² for full dosing; ≥ 30 but < 45 ml min⁻¹ 1.73 m² reduce dose to 1500 mg/day; < 30 → hold.
5. NSAID caution: Concurrent NSAIDs or ACE inhibitors can further impair renal clearance; review medication list before initiating.
6. Pregnancy safety: While Category C, meta‑analyses show no increased teratogenicity; many obstetricians continue therapy with close monitoring.
7. Vitamin B12 screening: Metformin inhibits B12 absorption; baseline and yearly checks prevent pernicious anemia.
8. Weight benefits: Up to 5 kg weight loss reported in 50 % of overweight patients—advantageous in obesity‑linked T2DM.
9. Patient education: Teach patients to recognize early lactic acidosis symptoms and to report them immediately.
10. Use with caution in heart failure: Metformin may worsen acidosis risk; consider alternative agents in decompensated HF.
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• *(All information is current as of 2026. Consult the latest prescribing information and guidelines for updates.)*