Tirzepatide: The Complete Guide

What is Tirzepatide?

Tirzepatide is a first-in-class dual GIP and GLP-1 receptor agonist developed by Eli Lilly. Unlike semaglutide which only targets the GLP-1 receptor, tirzepatide simultaneously activates both the GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptors — two key incretin hormones involved in blood sugar regulation and appetite.

Approved by the FDA in 2022 for type 2 diabetes (as Mounjaro) and in 2023 for chronic weight management (as Zepbound), tirzepatide has quickly become one of the most sought-after medications in the space, largely due to its superior weight loss results compared to semaglutide.

Two Brand Names, One Molecule

How Tirzepatide Works

Tirzepatide's dual mechanism is what sets it apart from other GLP-1 medications:

• GLP-1 receptor activation — Like semaglutide, it suppresses appetite, slows gastric emptying, and improves insulin secretion.
• GIP receptor activation — The addition of GIP activity enhances fat metabolism, improves insulin sensitivity in adipose tissue, and may contribute to the greater weight loss seen in trials. GIP also appears to help mitigate some of the nausea associated with GLP-1 alone.
• Synergistic effects — The two hormones working together produce metabolic improvements greater than either would alone, including better glucose control, more fat loss, and potentially improved body composition.

Clinical Trial Results

SURMOUNT Trials (Weight Management)

The SURMOUNT program studied tirzepatide for weight management, and the results were unprecedented:

• SURMOUNT-1: At the highest dose (15 mg), participants lost an average of 22.5% of body weight over 72 weeks — with over a third losing 25% or more.
• SURMOUNT-2 (in patients with type 2 diabetes): Average weight loss of 14.7% at the highest dose.
• SURMOUNT-3 (after intensive lifestyle intervention): Average weight loss of 26.6% — the highest ever recorded for a non-surgical intervention.
• SURMOUNT-4 (withdrawal study): Patients who continued tirzepatide maintained their weight loss, while those switched to placebo regained significant weight — reinforcing the need for continued treatment.

SURPASS Trials (Diabetes)

The SURPASS program studied tirzepatide for type 2 diabetes and showed superior A1C reduction compared to semaglutide, insulin, and other diabetes treatments, with up to 2.4% A1C reduction from baseline.

Dosing Schedule

Like semaglutide, tirzepatide uses gradual dose escalation. The steps are larger and the titration period is longer.

Not all patients need to reach 15 mg. Many achieve their goals at 10 or 12.5 mg. Your provider will help determine the right maintenance dose based on your response and tolerability.

Side Effects

Tirzepatide's side effect profile is similar to semaglutide, though some evidence suggests the GIP component may slightly reduce the severity of nausea.

Very Common (>10%)

• Nausea (~29%) — generally milder than semaglutide in some trials
• Diarrhea (~23%)
• Decreased appetite (~20%)
• Vomiting (~12%)
• Constipation (~11%)

Serious (Rare)

• Pancreatitis
• Gallbladder disease
• Thyroid C-cell tumors (same boxed warning as semaglutide)
• Hypoglycemia (primarily when combined with insulin or sulfonylureas)

Cost & Insurance

• Mounjaro: ~$1,000–$1,100/month (list price)
• Zepbound: ~$1,000–$1,100/month (list price)

Eli Lilly has been aggressive with savings programs. The Zepbound savings card can bring costs down to $550/month for cash-pay patients and as low as $25/month for commercially insured patients. Lilly also launched LillyDirect, a direct-to-patient platform offering competitive pricing.

Compounded tirzepatide became available when the drug was on the FDA shortage list, though availability through this channel may change as supply normalizes.

Tirzepatide vs. Semaglutide

This is the most common comparison patients ask about. Here's how they stack up: