Generic Name

Giazo

Mechanism

Giazo is a selective antagonist of the ghrelin (GHS‑R1a) receptor.
• Competitive inhibition of ghrelin binding prevents downstream activation of the growth hormone secretagogue pathway.
• Reduction in ghrelin signaling → decreased appetite and caloric intake.
• Modest inhibition of ghrelin‑induced stimulation of growth hormone release, contributing to a modest metabolic shift.

Pharmacokinetics

• Route & Absorption: Oral capsule, 95 % bioavailability; Tmax ~2 h.
• Distribution: Moderate plasma protein binding (~65 %).
• Metabolism: Primarily CYP3A4‑mediated N‑dealkylation; minor CYP2D6 pathway.
• Elimination: Renal (approx. 55 %) and biliary (45 %) excretion.
• Half‑life: 12–14 h; steady state achieved within ~4 days.

Indications

• FDA‑approved for chronic weight management in adults with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² with comorbidities.
• Off‑label use: adjunctive therapy for mild‑to‑moderate anxiety disorders (benefits of appetite modulation and neuroendocrine stress relief).

Contraindications

• Contraindications:

* Severe hepatic impairment (Child‑Pugh C).

* Pregnancy and lactation—data on teratogenicity unavailable.

* Concomitant use of potent CYP3A4 inhibitors (e.g., itraconazole).
• Warnings:

* Potential hepatotoxicity—monitor LFTs.

* QT interval prolongation—avoid in patients with congenital long‑QT syndrome or on other QT‑extending agents.

Dosing

• Initial dose: 10 mg once daily (OD) in the morning.
• Titration: Increase by 10 mg every 4 weeks to a maximum of 40 mg OD if tolerated.
• Take with food to enhance absorption.
• Pauses: 24‑hr drug holiday recommended if signs of dizziness or orthostatic hypotension.

Adverse Effects

• Common (≤ 10 %):

* Nausea, vomiting, constipation.

* Headache, mild dizziness.

* Mild transient hypophosphatemia.
• Serious (> 1 %):

* Elevated liver enzymes (≥ 3 × ULN).

* QT prolongation (> 460 ms).

* Severe allergic reactions (rash, angioedema).

* Rare cases of pancreatitis (presenting with epigastric pain and elevated lipase).

Monitoring

• Baseline: LFTs, renal profile, serum electrolytes, ECG.
• Follow‑up:

* LFTs every 3 months (or sooner if symptoms).

* ECG every 6 months if on concurrent QT‑prolonging drugs.

* Weight and BMI every 2 weeks during titration.

* Monitor blood glucose if patient has diabetes mellitus.

Clinical Pearls

• Ghrelin antagonism = appetite suppression without significant appetite‑driven cortisol release—advantage in patients with metabolic syndrome.
• Drug–Drug Interactions: Overlap with CYP3A4 substrates (e.g., statins, oral contraceptives) may alter plasma levels—dose adjustment may be needed.
• Comorbid Depression: Patients may experience transient mood swings; consider integrating CBT during weight‑loss program.
• Education: Reinforce dietary compliance—Giazo reduces appetite but does not replace the need for caloric restriction.
• Contraindication Clue: If a patient presents with elevated transaminases within 2 weeks of therapy, immediately discontinue.

Disclaimer: The data above are synthesized for educational purposes and reflect a hypothetical pharmacologic profile. For actual prescribing, consult peer‑reviewed literature and product labeling.