GLP-1 Agonists Weight Loss Dual GIP/GLP-1 Agonists Multiple Incretin Agonists Gastrointestinal Peptides Peptide Hormones Approved

Tirzepatida

Also known as: Mounjaro, Zepbound, LY3298176

Tirzepatide is a synthetic dual GIP (gastric inhibitory polypeptide) and GLP-1 receptor agonist approved by the FDA in 2022. It represents the next generation of metabolic therapies, surpassing selective GLP-1 agonists (semaglutide) in weight loss efficacy. Manufactured by Eli Lilly.

Mechanism of action

First clinically approved "twincretin" molecule. Its dual mechanism integrates:

GIP: Stimulates insulin (beta cells), inhibits glucagon, improves insulin sensitivity in adipose tissue and promotes lipolysis. GIP also acts centrally in weight regulation
GLP-1: Same effects as semaglutide. Gastric emptying delay and central appetite reduction

Uses & indications

Type 2 diabetes mellitus (Mounjaro®, FDA 2022)
Obesity and overweight (Zepbound®, FDA 2023)
Heart failure with preserved ejection fraction (HFpEF) in obese patients (FDA 2024)
Obstructive sleep apnea (FDA 2024)

Effects

Beneficial effects: Weight reduction of 20–22.5% of body weight (SURMOUNT-1, 15 mg dose), superior to semaglutide 2.4 mg (~15%). HbA1c reduction of 1.87–2.07%. 38% reduction in CV events in HFpEF (SUMMIT).

Adverse effects: Similar to GLP-1 agonists: nausea, vomiting, diarrhea, constipation. Same precautions as semaglutide.

Considerations & contraindications

Same contraindications as semaglutide (MTC, MEN2)
Do not use during pregnancy (discontinue ≥1 month before conception)
Limited data in severe renal/hepatic impairment
May reduce absorption of oral contraceptives

Regulatory approval

FDA approved: Mounjaro® (T2D, May 2022), Zepbound® (obesity, November 2023), HFpEF with obesity (2024), Obstructive sleep apnea (2024). EMA approved with equivalent indications.

Dosage

T2D: start 2.5 mg/week × 4 weeks → escalation every 4 weeks (5 → 7.5 → 10 → 12.5 → 15 mg). Obesity: same protocol up to 15 mg.

Storage

Prefilled pens: 2–8°C. Once opened, ≤30°C up to 21 days.

Technical data

Regulatory status Approved

Molecular weight 4813.47 Da

Half-life ~5 días

Administration routes Subcutánea semanal