Tirzepatide

Tirzepatide is a dual GIP/GLP-1 receptor agonist, the first drug in its class. It is a single synthetic molecule that binds to both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor simultaneously. This dual agonism produces additive effects on appetite suppression, insulin secretion, and energy expenditure that exceed what GLP-1 agonists alone can achieve.

In the SURMOUNT-1 clinical trial, adults with obesity treated with tirzepatide 15 mg weekly for 72 weeks achieved a mean body weight reduction of 22.5%, with 63% of participants achieving ≥20% weight loss. These results significantly exceed those seen with semaglutide in comparable trials. The SURPASS series of diabetes trials showed tirzepatide reduced HbA1c by 1.87–2.07%, among the largest reductions ever documented for a weekly injectable.

Tirzepatide vials for research use typically come in 10 mg sizes. The most common reconstitution is 2 mL BAC water, giving a concentration of 5 mg/mL. At 2.5 mg doses, that is 0.5 mL or 50 units on a U-100 syringe, a comfortable draw volume. For lower doses (2.5 mg starter), some prefer 4 mL of BAC water to get 2.5 mg/mL concentration, which doubles the draw volume and allows for more precise measurement at lower doses.

Injection sites, technique, and syringe selection are identical to semaglutide. Use a 29–31 gauge subcutaneous needle. Rotate injection sites each week across the abdomen, outer thighs, and upper arms. Refrigerate at 2–8°C after reconstitution and discard after 28 days. Do not freeze. The peptide should remain clear; cloudiness or precipitation indicates degradation.

GI side effects (nausea, vomiting, diarrhea, constipation) are the primary tolerability concern, identical in character to semaglutide but potentially more pronounced at higher doses due to the dual mechanism. Slow titration, 4 weeks minimum at each step, dramatically reduces GI burden. Most people find GI tolerance improves significantly after the first 4–8 weeks as the body adapts. Eating slowly, in smaller portions, and avoiding very fatty meals helps during titration.