Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)
2,539 adults with obesity or overweight, no diabetes
Average weight change at 72 weeks was -15.0% (5 mg), -19.5% (10 mg) and -20.9% (15 mg) vs -3.1% on placebo.
Read the studyA once-weekly GIP and GLP-1 dual agonist approved for type 2 diabetes, heart risk in diabetes, obesity and sleep apnea.
Also called Mounjaro, Zepbound, LY3298176
Tirzepatide is a single 39-amino-acid peptide that switches on two gut hormone receptors at once: GIP and GLP-1. It is built on the GIP backbone, carries a fatty acid tail that binds albumin, and lasts about 5 days in the blood, so it is injected once a week. Eli Lilly sells it as Mounjaro for type 2 diabetes and Zepbound for weight management and obstructive sleep apnea.
It produces more weight loss than semaglutide 2.4 mg. In SURMOUNT-1, 2,539 adults without diabetes lost an average of 20.9% of body weight over 72 weeks on 15 mg, against 3.1% on placebo. In SURMOUNT-5, a head-to-head trial in 751 adults, it averaged -20.2% versus -13.7% for semaglutide. In people with prediabetes, 3 years on tirzepatide cut new type 2 diabetes from 13.3% to 1.3%. SUMMIT showed fewer heart failure events in HFpEF with obesity, and in SURPASS-CVOT it matched dulaglutide on heart attacks, strokes and cardiovascular deaths in type 2 diabetes; in August 2026 FDA added a Mounjaro indication to lower that risk in adults with type 2 diabetes at high cardiovascular risk.
Side effects mirror semaglutide: nausea, diarrhea, vomiting and constipation, mostly while the dose goes up, plus gallbladder disease and rare pancreatitis. Weight returns after stopping: in SURMOUNT-4, people switched to placebo regained 14% of their weight over a year while those who stayed on it kept losing. Tirzepatide is an approved prescription drug, not a research compound.
What it binds to, and what happens inside the body after that, step by step.
Tirzepatide activates the GIP receptor with roughly native-hormone strength and the GLP-1 receptor somewhat more weakly than native GLP-1. Together these raise glucose-dependent insulin release, lower glucagon, slow stomach emptying and cut appetite through receptors in the brain. Why adding GIP gives more weight loss than GLP-1 alone is still debated; animal work points to GIP acting in appetite centers and on fat tissue.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
The SURPASS (diabetes) and SURMOUNT (obesity) programs include more than 20 randomized trials. They show about 20% average weight loss at the top dose, larger glucose and weight effects than semaglutide in direct comparisons, prevention of type 2 diabetes in prediabetes, improvement in sleep apnea and fewer heart failure events in HFpEF. A dedicated cardiovascular outcomes trial in obesity without diabetes (SURMOUNT-MMO) had not reported as of October 2026.
2,539 adults with obesity or overweight, no diabetes
Average weight change at 72 weeks was -15.0% (5 mg), -19.5% (10 mg) and -20.9% (15 mg) vs -3.1% on placebo.
Read the study751 adults with obesity, no diabetes
Weight change at 72 weeks was -20.2% on tirzepatide vs -13.7% on semaglutide; waist shrank 18.4 cm vs 13.0 cm.
Read the study1,032 adults with obesity and prediabetes
Over 176 weeks, 1.3% on tirzepatide vs 13.3% on placebo developed type 2 diabetes (hazard ratio 0.07).
Read the study469 adults with moderate to severe sleep apnea and obesity, two trials
Breathing interruptions fell by 25.3 to 29.3 events per hour vs about 5 on placebo at 52 weeks, from a baseline near 50.
Read the study731 adults with HFpEF and obesity
Cardiovascular death or worsening heart failure occurred in 9.9% vs 15.3% on placebo (hazard ratio 0.62).
Read the study1,879 adults with type 2 diabetes on metformin
HbA1c fell 2.01 to 2.30 points vs 1.86 on semaglutide 1 mg, with 1.9 to 5.5 kg more weight loss.
Read the study670 adults who lost 20.9% in a 36-week lead-in
Over the next 52 weeks, those kept on tirzepatide lost 5.5% more while those switched to placebo regained 14.0%.
Read the study13,165 adults with type 2 diabetes and atherosclerotic heart disease
Major cardiovascular events occurred in 12.2% vs 13.1% on dulaglutide (hazard ratio 0.92): noninferior, not proven superior.
Read the studyNo preclinical studies are listed as key studies here. The human data above carries the evidence.
These are questions the published research has not answered.
Prescription-only. Not on the WADA Prohibited List; WADA added tirzepatide markers to its Monitoring Program from January 1, 2026. The Zepbound label no longer lists a suicidal behavior and ideation warning (removed in 2026). Zepbound is also sold in single-dose vials and a multi-dose KwikPen. Mounjaro gained a US indication in August 2026 to lower the risk of major cardiovascular events in adults with type 2 diabetes at high cardiovascular risk. Not approved for heart failure as of October 2026 despite positive SUMMIT results.
How much of Tirzepatide is left after a single dose
Simple first-order model from the published half-life. Real clearance varies with dose, route, kidney and liver function and formulation. This is not a dosing schedule.
This table records the doses that trials and approved labels used, with the source for each row. It is a record of research, not a recommendation, and it is open to free members.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
Tap a claim to see what the studies found.
It produces more weight loss than semaglutide 2.4 mg (20.2% vs 13.7% in SURMOUNT-5) but it is a different molecule that also activates the GIP receptor. Semaglutide has proven heart, kidney and liver outcome data that tirzepatide does not yet have in people without diabetes.
In the SURMOUNT-1 body-scan subgroup, fat mass fell about three times more than lean mass in percentage terms, a ratio similar to diet-induced weight loss. Lean mass also includes water and organs.
Only Mounjaro and Zepbound are FDA-reviewed for identity, strength and sterility. Compounding copies stopped being permitted in 2025 after the shortage ended, and products sold as research chemicals have no quality oversight.
The label says it may reduce oral contraceptive effect because of slower stomach emptying, mostly after the first dose and dose increases. It advises a backup or non-oral method for 4 weeks after starting and after each increase.
In SURMOUNT-4, people switched to placebo after 36 weeks regained 14% of their weight over the next year, and fewer than 1 in 5 kept at least 80% of their loss.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
Discussed online as an amylin add-on to tirzepatide, by analogy with CagriSema.
EvidenceNot studied together in published human trials. All amylin plus incretin human data come from cagrilintide plus semaglutide.
Sometimes proposed to push weight loss further.
EvidenceNever studied together. The Zepbound label says not to combine it with any GLP-1 receptor agonist.
Not applicable: approved tirzepatide is supplied as a ready-to-use solution in pens, vials or a multi-dose KwikPen.
Refrigerate at 36 to 46 F (2 to 8 C), do not freeze. Single-dose pens and vials can stay unrefrigerated up to 86 F (30 C) for up to 21 days and should not go back in the fridge. Multi-dose vials and KwikPens are discarded 30 days after first use or after 4 weekly doses.
One email when a trial reads out, a label changes or the FDA acts on a peptide. Free, no selling of peptides, unsubscribe any time.