Tirzepatide

Tirzepatide (dual GLP-1/GIP agonist)

Dual GLP-1 + GIP receptor agonist · most effective weight-loss peptide approved

FDA Status

FDA-approved · Mounjaro (T2D) 2022 · Zepbound (obesity) 2023

Class

Dual incretin agonist · 39 amino acids · pegylated

Sequence

Modified GLP-1 backbone with GIP-targeting substitutions

Half-life

~5 days · once-weekly subcutaneous

Mechanism of action

• Simultaneous activation of GLP-1 and GIP receptors
• GIP-mediated adipocyte function modulation
• Insulinotropic effect amplified vs single-receptor agonists
• Direct hypothalamic appetite suppression

Research areas

• Obesity: SURMOUNT-1 trial showed up to 22.5% body weight reduction at 15 mg
• Type 2 diabetes: SURPASS trials, ~2.4% HbA1c reduction
• NASH and metabolic-associated fatty liver disease
• Cardiovascular outcome trials (SURMOUNT-MMO ongoing)

Evidence and clinical data

Head-to-head superior to semaglutide in SURPASS-2 (greater HbA1c and weight reduction at all doses). Strongest weight-loss data of any approved drug class to date.

Safety profile

Similar safety profile to semaglutide. GI effects predominate. Long-term cardiovascular safety being established in ongoing trials.