Zepbound
Zepbound
Generic Name
Zepbound
Mechanism
- Dual Incretin Mimetic
- GLP‑1 Receptor Activation → ↑ insulin secretion, ↓ glucagon release, delayed gastric emptying, reduced appetite.
- GIP Receptor Activation → synergistic insulinotropic effect and modulation of adipocyte metabolism.
- Combined activity leads to:
- Improved glycaemic control.
- Significant satiety induction → reduced caloric intake.
- Enhanced energy expenditure via adipose tissue browning.
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Pharmacokinetics
| Parameter | Details |
| Route | Subcutaneous injection (once weekly) |
| Absorption | Peak plasma concentration 24–48 h post‑dose; ~90 % bioavailability relative to intramuscular route. |
| Distribution | Protein‑binding 54‑65%; mean volume of distribution ~20 L. |
| Metabolism | Mainly proteolytic degradation; no major CYP involvement. |
| Elimination | Half‑life ~5 days; elimination is primarily renal/urinary. |
| Dose‑Response | Linear up to 15 mg; receptor occupancy 70‑80 % at therapeutic dose. |
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Indications
| Indication | Recommended Dose | Typical Weight Loss | Typical HbA1c ↓ |
| Obesity | Start 5 mg SC weekly → titrate dose weekly to 10 mg (after 4 wk) and 15 mg (after an additional 8 wk) | 25 % ±5 % body‑weight loss at 68 wk | N/A |
| Type 2 Diabetes | Start 2.5 mg SC weekly → titrate to 15 mg over 14 wk | 4‑5 % body‑weight loss | 1.3‑1.5 % HbA1c reduction |
*Note*: Product monograph should be consulted for regulatory specificities per jurisdiction.
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Contraindications
- Contraindications
- Known hypersensitivity to tirzepatide or any excipients.
- Concurrent use of insulin‑promoting agents in uncontrolled diabetes (risk of hypoglycaemia).
- Pregnancy (data insufficient).
- Warnings
- Pancreatitis: Rare but serious; discontinue if acute pancreatitis occurs or if serum lipase ↑ ≥4× ULN.
- Thyroid C‑cell Tumors: Data from rodent studies suggest dose‑dependent tumorigenesis; avoid in patients with a history of medullary thyroid carcinoma or MEN 2 syndromes.
- Eye Disorders: Monitor for changes in vision; avoid in patients with ocular diseases requiring frequent eye exams.
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Dosing
- Obesity (Zepbound)
1. Weeks 1–4: 5 mg once weekly.
2. Weeks 5–12: 10 mg once weekly.
3. Weeks 13+: 15 mg once weekly (maintain).
• T2DM (tirzepatide)
1. Weeks 1–4: 2.5 mg once weekly.
2. Weeks 5–8: 5 mg once weekly.
3. Weeks 9–12: 7.5 mg once weekly.
4. Weeks 13+: 10 mg, then 12.5 mg, then 15 mg, as tolerated.
_Administration_:
• Rotate injection sites (abdomen, thigh, upper arm).
• Advise patient on technique and precaution for injection‑site reactions.
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Adverse Effects
| Category | Common (≥10 %) | Less Common (1–10 %) | Serious (≥0.1 %) |
| Gastro‑intestinal | Nausea, vomiting, diarrhoea, abdominal pain | Dysphagia, constipation | Pancreatitis, gallbladder disease |
| Injection‐site | Erythema, pruritus, edema | Lipoatrophy | Rare allergic reaction |
| Metabolic | Hypoglycaemia (co‑administered agents) | Hyper‑ or hypoglycaemia with non‑insulin drugs | Severe hypoglycaemia requiring assistance |
| Endocrine | Weight loss (desired) | Thyroid hormone alterations | Thyroid C‑cell tumour (reported in rodents) |
| Neurological | Headache | Dizziness | Severe central nervous system disturbance (none reported) |
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Monitoring
| Parameter | Frequency | Rationale |
| Baseline labs | HbA1c, fasting plasma glucose, serum lipase, total TSH, serum thyroglobulin (if risk factors) | Establish gravity, rule out baseline pancreatitis or thyroid disease |
| During therapy | HbA1c every 12 wk (for T2DM) | Efficacy and adjustment |
| Weight | Every visit | Weight‑loss efficacy and side‑effect correlation |
| Pancreatic enzymes | Every 12 wk, or if symptoms | Detect subclinical pancreatitis |
| Vital signs & AEs | At each visit | General safety |
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Clinical Pearls
1. Dual‑Incretin Advantage – Tirzepatide’s GIP component improves insulin sensitivity in peripheral tissue, complementing GLP‑1’s incretin effect, which may account for superior efficacy versus GLP‑1 alone.
2. Obesity‑Specific Dosing – Obesity dosing (5/10/15 mg) begins at a higher initial dose than T2DM dosing, yielding faster satiety and early weight loss, vital for patient motivation.
3. Pancreatitis Vigilance – The signal is rare but serious; only 1 in 10,000 patients experienced pancreatitis in pivotal trials. Patients should report new abdominal pain promptly.
4. Teratogenicity – Not studied in pregnant women; advise effective contraception for patients of childbearing potential.
5. Injection‑Site Reactions – Use systematic rotating sites and apply mild pressure post‑injection to reduce lipoma/lipoatrophy risk; this can improve adherence.
6. Weight‑Loss Monitoring – Targeting ≥5 % weight loss at 12 months meets the *clinical significance* threshold; focus on caloric intake, not overt lifestyle extremes.
7. Comorbidity Consideration – In patients with heart failure, tirzepatide may improve cardiovascular risk markers, but data are limited; monitor ejection fraction if using concomitant cardioprotectants.
8. Abdominal Symptoms – Distinguishing late‑onset, mild nausea from pancreatitis requires correlation with lipase; early CT imaging can be considered if suspicion is high.
9. Medication Interaction – Symptom overlap with other GI agents (e.g., metoclopramide) may mask nausea; consider opioid‑induced GI side‑effects separately.
10. Combination Therapy – Tirzepatide is frequently combined with SGLT‑2 inhibitors for synergistic glycaemic control; clinicians should be aware of potential additive weight loss and polyuria.
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• Key Takeaway: Safely harness the potent dual‑incretin action of Zepbound by following structured titration, vigilant monitoring for pancreatitis, and proactive management of injection‑site reactions, thereby unlocking superior weight‑loss and glycaemic outcomes for patients with obesity and type 2 diabetes.