Xultophy
Xultophy
Generic Name
Xultophy
Mechanism
Xultophy works synergistically through two pharmacologic pathways:
• Semaglutide – a GLP‑1 receptor agonist that stimulates glucose‑dependent insulin secretion, suppresses glucagon release, delays gastric emptying, and reduces appetite, leading to weight loss.
• Insulin degludec – a long‑acting basal insulin analogue that provides steady basal insulin coverage, lowering fasting plasma glucose and post‑prandial glucagon levels.
The combination allows once‑weekly GLP‑1 action with stable basal insulin, reducing the need for multiple daily injections.
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Pharmacokinetics
| Parameter | Semaglutide | Insulin degludec |
| Onset | 1–2 h after injection | 1–3 h (fast‑acting) |
| Peak | 4–8 h | No peak (steady) |
| Elimination | Hepatic clearance, t½ ≈ 160 h | Renal exclusion; t½ ≈ 25 h |
| Metabolism | Peptidase‑mediated; not dose‑dependent | Non‑renal; unaffected by CKD |
| Food interaction | Minimal | No significant effect |
• Same duration (≈ 7 days) facilitates weekly dosing.
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Indications
- Adults with T2DM who remain ≥ 0.5 % above HbA1c goal while on basal insulin ≥ 10 U or a GLP‑1 RA alone.
- Preferred when weight loss or appetite control is desired and to reduce the injection burden.
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Contraindications
| Contraindication | Warning | |
| Hypersensitivity to semaglutide, insulin degludec, or any excipients | Severe or uncontrolled hypoglycemia – dose adjustment prior to introduction | |
| History of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2) | Pregnancy and lactation – not recommended | |
| Active pancreatitis | Renal impairment (CrCl 50 U/day – consider alternative | Dizziness/lightheadedness during dose escalation – monitor fasting glucose |
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Dosing
- Initial dose: 0.25 mg semaglutide (pre‑filled syringe), 10 U insulin degludec.
- Step‑up schedule (if HbA1c > 7.5 %):
1. 1 week: 0.25 mg + 10 U
2. 3 weeks: 0.5 mg + 10 U
3. 6 weeks: 1.0 mg + 10 U
4. 9 weeks: 1.5 mg + 10 U (max).
• Insulin dose titration: adjust based on fasting glucose targets; usually ± 2 U weekly.
• Injection: subcutaneously into thigh, abdomen, or upper arm; rotate sites.
• Pin‑point: 9 cm from injection site to avoid penetration of insulin‑rich vein or fatty tissue.
Storage: −30 °C to +8 °C; keep in the refrigerator until the first use. Once opened, store at 2–8 °C and use within 24 h.
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Adverse Effects
| Category | Common | Serious |
| Gastro‑intestinal | Nausea, vomiting, diarrhea, constipation, abdominal pain | Severe nausea/vomiting → dehydration |
| Endocrine | Hypoglycemia (especially when added to other glucose‑lowering agents) | Hypoglycemia unawareness, severe hypoglycemia |
| Others | Injection site reactions (pain, erythema, edema) | Pancreatitis, thyroid C‑cell hyperplasia (rare) |
| Weight | Weight loss (≈ 1–3 kg over 6 mo) | Weight gain (due to insulin) |
• *Monitor glucagon‑like symptoms and report persistent GI upset.*
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Monitoring
- Baseline: HbA1c, fasting glucose, weight, renal function (eGFR), liver enzymes, thyroid profile in high‑risk populations.
- Periodic:
- HbA1c every 3 months.
- Fasting glucose 2–3 times/week during titration, then weekly.
- Weight every visit.
- Check for pancreatitis symptoms (abdominal pain, CT if needed).
- In patients > 65 y or those with renal impairment, increase frequency of hypoglycemia checks.
- Patient‑reported: Injection site changes, GI symptoms, dizziness.
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Clinical Pearls
- Weight Management Tool – Semaglutide’s appetite‑suppression effect makes Xultophy effective for weight loss in overweight T2DM patients; counsel patients that insulin may blunt weight loss slightly.
- Simplified Regimen – A single weekly pen reduces injection fatigue and improves adherence versus multiple daily basal+prandial insulin or GLP‑1 RA schedules.
- Start Low, Go Slow – Initiate with the lowest semaglutide dose (0.25 mg) and titrate weekly; this mitigates GI distress and early hypoglycemia.
- Renal Considerations – Insulin degludec is not renally cleared; no dose adjustment needed for CKD, but monitor for hypoglycemia due to decreased hepatic clearance.
- Pregnancy – Xultophy is contraindicated; switch to basal insulin alone if conception is intended.
- Beta‑Blocker Overlap – If on beta‑blockers, hypoglycemia may be masked; advise glucometer checking prior to bedtime and during titration.
- Education – Reinforce proper syringe handling: detach pen ink, re‑prime, ensuring single‑use; re‑introduce injection sites to avoid lipohypertrophy.
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• Key Takeaway: Xultophy harnesses the complementary glucose‑lowering profile of a GLP‑1 RA and basal insulin within one weekly pen, offering clinicians a streamlined, weight‑friendly option for adults with T2DM who need more robust glycaemic control.