Wegovy
Wegovy®
Generic Name
Wegovy®
Mechanism
- GLP‑1 receptor activation: Mimics endogenous GLP‑1 → stimulates pancreatic β‑cell insulin secretion (glucose‑dependent) and inhibits glucagon release.
- Central suppression of appetite: Acts on the arcuate nucleus of the hypothalamus via CNO1 and POMC pathways → reduces food intake and early satiety.
- Slows gastric emptying: Prolongs meal duration, enhancing satiation.
- Energy expenditure: Shown to modestly increase resting metabolic rate.
The combination of peripheral and central effects lowers caloric intake and improves glycemic control, leading to sustained weight loss (~15‑20 % of body weight in trials).
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Pharmacokinetics
| Parameter | Details (Semaglutide) |
| Absorption | Subcutaneous; peak serum concentration ~4 days post‑dose. |
| Volume of Distribution | ~0.5 L/kg. |
| Metabolism | Proteolytic degradation (peptidases) and hydrolysis; not reliant on hepatic CYP450 enzymes. |
| Half‑life | ~7 days (supports once‑weekly dosing). |
| Route of Elimination | Urinary excretion mostly metabolite; <1 % unchanged drug. |
*Note: Renal impairment does not require dose adjustment.*
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Indications
- Adults (≥18 yr) with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² + at least one weight‑associated comorbidity (e.g., hypertension, type 2 diabetes mellitus, dyslipidemia).
- Provided the patient is concurrently on a non‑restrictive diet and increasing physical activity.
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Contraindications
- Contraindications:
- Personal or family history of medullary thyroid carcinoma (MTC).
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Warnings:
- Hypoglycemia (especially when combined with insulin or sulfonylureas).
- Pancreatitis: Monitor symptoms; discontinue if suspected.
- Gallbladder disease: Assess risk as GLP‑1 RAs may precipitate gallstones.
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Dosing
| Step | Dose (weekly) | Duration | Titration Notes |
| 0 | 0.25 mg | 4 weeks | Initiate low dose to reduce GI AEs. |
| 1 | 0.5 mg | 4 weeks | Continue if tolerated. |
| 2 | 1.0 mg | 4 weeks | Standard maintenance dose. |
| 3 | 1.7 mg | 4 weeks | Most patients reach this final dose; 2.4 mg is alternative for weight loss research. |
• Form: Pre‑filled pen; inject SC in abdomen, thigh, or upper arm.
• Timing: Same day of week; at any time of day regardless of meals.
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Adverse Effects
Common (≥ 10 %)
• Nausea, vomiting, diarrhea
• Anorexia, abdominal pain
• Headache, dizziness
• Injection‑site reactions (erythema, induration)
Serious (≤ 1 %)
• Pancreatitis
• Thyroid C‑cell tumors (rare in humans; animal data)
• Acute kidney injury (due to volume depletion)
• Severe hypoglycemia (when used with other antihyperglycemics)
*Management*: Gradual uptitration, antiemetics, hydration, and routine labs.
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Monitoring
| Parameter | Frequency | Purpose |
| Weight | Every 4 weeks | Assess efficacy; adjust therapy. |
| HbA1c / FPG | Every 12 weeks (or sooner if on diabetes meds) | Gauge glycemic impact. |
| Renal function (CrCl) | Baseline, then every 6 months | Semaglutide not renally cleared, but monitor for volume status. |
| Liver enzymes | Baseline, then annually | No known hepatotoxicity but monitor GP. |
| Thyroid C‑cell markers (TSH, Tg) | Baseline, then yearly | Screen for malignancy. |
| GI tolerance | Every visit | Address nausea, vomiting. |
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Clinical Pearls
- “First‑step forget‑point”: The 0.25 mg priming dose dramatically reduces early GI side‑effects; skip it only if the patient is highly tolerant, but cost constraints often limit usage.
- Diet synergy: Pairing Wegovy with a moderate‑calorie (~1200–1500 kcal) diet amplifies weight loss; however, over‑restrictive diets counteract appetite suppression and may trigger hyperphagia.
- Cardiovascular benefit: In the STEP trials, 26% of patients achieved ≥ 15 % weight loss and a 30% reduction in composite cardiovascular events, supporting its role beyond BMI reduction.
- Insulin users: Proactively lower insulin doses within 2–4 weeks to avoid hypoglycemia; monitor plasma glucose every 2–3 days during titration.
- Screen for gallbladder disease: Baseline abdominal ultrasound recommended for patients > 45 yr or with prior gallstone history, as GLP‑1 RAs can slow gallbladder motility.
- Persistent nausea: If nausea persists after 6 weeks at 1.0 mg, consider adding ondansetron 4 mg PO TID; if ineffective, revert to 0.5 mg and reassess.
- Injection technique: Rotate sites to prevent lipodystrophy; volumes never exceed the pen’s full capacity.
- Pregnancy: Semaglutide is Category B; use only if benefits outweigh potential fetal risks—prefer alternative OTC options.
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• *Wegovy offers a potent, safe option for obesity management when combined with lifestyle modification. Adherence to titration protocols and systematic monitoring optimizes efficacy and minimizes adverse events.*