Glumetza
Glumetza
Generic Name
Glumetza
Mechanism
- Tirzepatide is a *dual agonist* of the glucose‑dependent insulinotropic peptide‑1 (GLP‑1) receptor and the glucose‑dependent insulinotropic polypeptide (GIP) receptor.
- Activates both receptors → ↑ insulin secretion, ↓ glucagon release, and ↓ gastric emptying.
- Enhances satiety and reduces appetite → weight loss.
- Prolonged half‑life (~5–6 days) enables once‑weekly dosing.
Pharmacokinetics
| Parameter | Key Details |
| Absorption | Subcutaneous injection; peak plasma concentration ~3–5 days post‑dose. |
| Distribution | Moderate volume (≈ 20 L), protein binding ≈ ~ 50 %. |
| Metabolism | Peptide hydrolysis by plasma peptidases; not hepatically metabolized. |
| Elimination | Renal route; 50‑60 % excreted unchanged (creatinine clearance ≥ 30 mL/min). |
| Half‑life | 5‑6 days (steady‑state achieved in ~1 month). |
| Drug‑Drug Interactions | Minimal. Caution with concomitant GLP‑1 agents due to additive hypoglycemia risk. |
Indications
- Type 2 diabetes mellitus (T2DM), *uncontrolled* with diet, exercise, and/or oral antihyperglycemics.
- Replaces *metformin* or can be used additively.
- Weight management: improves glycemic control *and* induces significant weight loss (up to −14 % body weight).
Contraindications
| Category | Detail |
| Contraindicated |
• Known hypersensitivity to tirzepatide or excipients. • Active pancreatitis or personal/family history of medullary thyroid carcinoma (MTC). |
| Warnings |
• Ongoing or prior colorectal cancer: monitor stool; use COE/FOE. • Severe renal impairment (CrCl < 30 mL/min): use with caution; dose adjustment not required but monitor. • Pregnancy: Category X; avoid. • Lactation: excretion in breast milk minimal; avoid. |
| Precautions |
• Celiac disease, malabsorption syndromes: check HbA1c response. • Concomitant use with other incretin therapies increases hypoglycemia risk. |
Dosing
- Initial Dose: 5 mg once weekly (subcutaneous) for 4 weeks.
- Titration: Increase to 10 mg weekly at week 4; then 15 mg at week 8; 20 mg at week 12; 25 mg at week 18; 30 mg at week 22.
- Maintenance: 30 mg once weekly (or 25 mg if side‑effect intolerance).
- Administration: Any arm, thigh, or abdomen; rotate sites; store at 2–25 °C; do not freeze.
- Missed Dose: If > 48 h missed, restart at 5 mg; otherwise, give at next scheduled time.
Adverse Effects
| Common (≥ 5 %) | Serious |
| Nausea, vomiting, diarrhea, abdominal pain | Pancreatitis (rare, < 1 %) |
| Injection‑site reactions | Serious hypersensitivity |
| Decreased appetite | Severe hypoglycemia (when combined with sulfonylureas/insulin) |
| Weight loss | Thyroid C‑cell tumors (preclinical) – monitor BRAF V600E |
| Headache | |
| Dyspepsia |
Monitoring
- Baseline: HbA1c, FPG, weight, lipid panel, renal function, liver enzymes.
- Periodic (every 3–6 months): HbA1c, weight, BP; review adverse events.
- If pancreatitis suspected: serum amylase/lipase; abdominal imaging.
- Cancer screening: Annual colorectal screening for all patients; GI symptoms warrant prompt evaluation.
Clinical Pearls
- Weight‑Centric Benefits: Glumetza consistently yields > 10 % weight loss in T2DM patients—useful for obesity‑related comorbidities.
- Dose‑Titration Matters: Rapid escalation (> 2 mg/week) increases GI AEs; maintain a 4‑week ramp for tolerance.
- Avoid Dual Incretin Therapy: Combining tirzepatide with another GLP‑1 agonist or DPP‑4 inhibitor rarely adds benefit and may elevate bleeding risk.
- Insulin Interaction: If using insulin, reduce to 20–30 % of baseline dose at the start of tirzepatide to mitigate hypoglycemia.
- Renal Safety: No dose adjustment needed in CrCl 30–90 mL/min but monitor renal function; safe in moderate CKD, contraindicated in ESRD.
- Injection Technique: Use a 4 mm‑long 27–30 G needle. Rotating sites reduces local reactions and improves absorption.
Reference‑Friendly: All data are derived from FDA labeling, pivotal phase III trials (SURPASS‑1 to 7), and peer‑reviewed pharmacology texts (e.g., Goodman & Gilman's *The Pharmacological Basis of Therapeutics*).