Dual GLP-1/GIP Receptor Agonist
FDA Approved

Tirzepatide

Mounjaro / Zepbound

Manufactured by Eli Lilly · Subcutaneous injection

Avg Weight Loss

~22

Dosing

Once weekly

Brand Cost

$1,000-1,200

Compounded

$200-500

How It Works

Tirzepatide is a first-in-class dual incretin agonist that activates both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. GLP-1 activation stimulates insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite. GIP activation enhances insulin sensitivity and may improve fat metabolism. The dual mechanism produces greater weight loss and glycemic control than GLP-1 agonists alone.

Mounjaro (Type 2 Diabetes) Zepbound (Weight Management)

Dosing & Titration

Tirzepatide

2.5mg 5mg 7.5mg 10mg 12.5mg 15mg

Titration Protocol

Start at 2.5mg weekly for 4 weeks (initiation dose, not therapeutic), increase to 5mg weekly. May increase by 2.5mg increments every 4 weeks based on response and tolerability. Maximum dose: 15mg weekly.

Common Side Effects

Common Nausea Common Diarrhea Common Decreased appetite Common Vomiting Common Constipation Common Dyspepsia Common Abdominal pain Common Injection site reactions

Serious Risks

Pancreatitis (rare)

Thyroid C-cell tumors (observed in rodent studies; relevance to humans unknown)

Gallbladder disease

Hypoglycemia (when used with insulin or sulfonylureas)

Acute kidney injury (from dehydration due to GI effects)

Severe allergic reactions including anaphylaxis

Cost Comparison

Brand Name

$1,000-1,200

per month

Compounded

$200-500

per month

Pharmacy Options

Brand (retail), Compounded 503A, Compounded 503B

Insurance Coverage

Covered by many commercial plans for Type 2 Diabetes (Mounjaro). Zepbound coverage for weight management is expanding but remains inconsistent. Prior authorization typically required. Eli Lilly offers savings cards for eligible commercial patients.

Pros & Cons

Advantages

  • Dual GLP-1/GIP mechanism produces greater weight loss than GLP-1 alone
  • Industry-leading weight loss results among approved medications (~22.5%)
  • Once-weekly dosing
  • Superior glycemic control vs semaglutide in head-to-head trials
  • Wide dose range allows individualized titration

Disadvantages

  • GI side effects during titration
  • Injection only (no oral formulation yet)
  • Supply shortages (though improving)
  • High cost without insurance
  • Less long-term safety data than semaglutide

Clinical Evidence

Clinical Trial Programs

SURMOUNT program (weight management: SURMOUNT-1 through SURMOUNT-4, MMO cardiovascular outcomes trial ongoing), SURPASS program (Type 2 Diabetes: SURPASS 1-5, SURPASS-CVOT)

surmount1

22.5% mean weight loss at 15mg vs 2.4% placebo over 72 weeks. 63% of participants achieved >=20% weight loss.

surpass2

Superior A1C reduction vs semaglutide 1mg (-2.5% vs -1.9%)

Contraindications

  • Personal or family history of medullary thyroid carcinoma (MTC)
  • Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
  • Known serious hypersensitivity to tirzepatide or any excipients

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