Tirzepatide

Mounjaro · Zepbound · S-tier (Dr. Alex Tatem) · Strong evidence

The most effective weight-loss drug you can get legally with a prescription today. It beat semaglutide head to head.

Dr. Tatem’s take

S-tier. He puts it there for its historic impact even though retatrutide is stronger. On Diary of a CEO he said it “produces more weight loss per milligram than any other product” and that he personally takes “a small dose”.

In Dr. Tatem’s tier list

• History: semaglutide (Wegovy/Ozempic) exploded in the late 2010s, but its benefit comes mainly from eating less — basal metabolic rate barely changes.
• Tirzepatide added the GIP receptor (gastric inhibitory peptide), which helps insulin secretion and changes fat metabolism, so it “finally started to move the needle” on metabolism and visceral (belly) fat.
• As of now it’s the best GLP-1 you can get from a regular pharmacy, and far safer than any old-school fat burner.
• Retatrutide will be stronger, but he gives tirzepatide the same S tier for what it did and the drive it sparked in the industry.

History & background

Tirzepatide was developed by Eli Lilly as a single molecule that activates both GIP and GLP-1 receptors. FDA approved it as Mounjaro for type 2 diabetes in May 2022 and as Zepbound for chronic weight management in November 2023, then for obstructive sleep apnea with obesity in December 2024.

In the head-to-head SURMOUNT-5 trial it produced 20.2% weight loss versus 13.7% for semaglutide. Shortages in 2022–2024 drove a boom in compounded versions; the shortage officially ended in December 2024.

Benefits

• Average weight loss of 15–21% at 72 weeks, depending on dose (SURMOUNT-1).
• More weight loss than semaglutide head to head: 20.2% vs 13.7% (SURMOUNT-5).
• Better blood-sugar control than semaglutide 1 mg (SURPASS-2).
• Approved for obstructive sleep apnea with obesity.

Risks

• Boxed warning for thyroid C-cell tumors. Don’t use it with a personal or family history of medullary thyroid cancer or MEN2.
• Pancreatitis, gallbladder disease, dehydration-related kidney injury.
• Nausea, diarrhea, constipation, especially while stepping up the dose.
• Aspiration risk under anesthesia because the stomach empties slowly. Tell your anesthesiologist.
• May make oral contraceptives less effective.
• Weight tends to come back after stopping.

Dosing protocols (informational, labeled by evidence)

• Clinical trial / label: FDA label (Zepbound/Mounjaro) — Start 2.5 mg/wk × 4 wk, then +2.5 mg every ≥4 wk; maintenance 5, 10 or 15 mg, SubQ, Weekly, Chronic
• Clinical trial / label: SURMOUNT-1 — 5, 10 or 15 mg/wk, SubQ, Weekly, 72 wk
• Community (bro science): 'Microdosing' — Commonly circulated ~1–2.5 mg/wk or less, sometimes split, SubQ, Weekly or split, Ongoing

Status: FDA-approved: Mounjaro (type 2 diabetes) and Zepbound (weight management; obstructive sleep apnea with obesity). The shortage has ended, so compounded versions are now restricted.

Grade and commentary: Dr. Alex Tatem. Watch: Truth About Popular Peptides Tier List (What Works, What’s Overhyped) | Pt. 3, Peptide Expert: What Do Peptides Actually Do? (EXPLAINED) - Dr Alex Tatem. Subscribe: @DrAlexTatem.