What the large trials and four FDA approvals show for blood pressure, the heart, sleep apnea, the liver and diabetes prevention, and how tirzepatide compares with semaglutide when the two are tested head to head.
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Tirzepatide is best known as the weight-loss drug that outperformed semaglutide. But the more interesting story is what happened in the trials that measured something other than the scale: blood pressure, heart-failure hospitalizations, breathing during sleep, liver inflammation and new cases of diabetes.
This article walks through that evidence trial by trial, with the actual numbers. It covers what earned an FDA approval, what is still at an earlier stage, what didn’t go as planned, and what none of these trials can tell you about a product they didn’t test. It’s a companion to our article Semaglutide, beyond the scale, and the two are compared side by side at the end.
After a meal, the gut releases two hormones that tell the pancreas to release insulin and tell the brain you’ve eaten: GLP-1 and GIP. Semaglutide mimics GLP-1 only. Tirzepatide is a single 39-amino-acid peptide engineered to activate both receptors, which is why it’s often called a dual agonist.
Like semaglutide, it carries a fatty-acid side chain that lets it bind to albumin in the blood, slowing its clearance enough for once-weekly dosing. Why adding GIP produces more weight loss is still being worked out; the trials below show that it does, not exactly how. We’ll look at the chemistry of the two molecules, and why both are demanding to manufacture, in a follow-up article.
| Approved | Use | Brand and key trials |
|---|---|---|
| May 2022 | Blood-sugar control in type 2 diabetes, later extended to children 10 and older | Mounjaro · SURPASS program |
| Nov 2023 | Chronic weight management in adults with obesity, or overweight plus a weight-related condition | Zepbound · SURMOUNT program |
| Dec 2024 | Moderate-to-severe obstructive sleep apnea in adults with obesity | Zepbound · SURMOUNT-OSA |
| Aug 2026 | Lowering the risk of heart attack, stroke or cardiovascular death in adults with type 2 diabetes | Mounjaro · SURPASS-CVOT |
The sleep apnea and cardiovascular approvals matter because they rest on outcome trials, not just weight or blood-sugar numbers.6,8,10
Average change in body weight from the start of the trial.
As with every drug in this class, these are averages: some people lost far more and some lost little. The effect also depends on staying on treatment. In SURMOUNT-4, everyone took tirzepatide for 36 weeks and was then randomly assigned to continue or switch to placebo. Over the next year, those who switched regained 14.0% of their body weight, while those who continued lost another 5.5%.1,2
High blood pressure and high triglycerides are two of the main reasons excess weight raises heart risk, so SURMOUNT-1 tracked both.
Share of people with normal blood pressure at week 72.
Systolic pressure fell 6.8 mmHg more than on placebo, and diastolic pressure 4.2 mmHg more. Most of the drop came in the first 24 weeks and then held steady, and it was seen across starting blood-pressure levels. An analysis estimated that weight loss explained about two-thirds of the effect.3
Triglycerides, the blood fats most tied to excess weight and insulin resistance, fell by about 27% across the tirzepatide doses versus about 6% on placebo.1 In the SURPASS-2 diabetes trial, the 15 mg dose lowered triglycerides by 24.8%.13
Share of people who had a heart attack, stroke or cardiovascular death. Hazard ratio 0.92, an 8% lower risk.
This trial needs careful reading. Dulaglutide (Trulicity) is itself a GLP-1 drug with proven heart protection, so a placebo comparison would have been unethical in this high-risk group. The trial’s goal was to show tirzepatide was at least as good, and it met that goal. The 8% edge was not statistically significant on its own. Deaths from any cause were 16% lower with tirzepatide, but that wasn’t one of the outcomes the trial was designed to test, so it’s a signal rather than proof.4
On the strength of these results, the FDA approved Mounjaro in August 2026 to reduce the risk of heart attack, stroke and cardiovascular death in adults with type 2 diabetes.10 A separate outcome trial in people with obesity but without diabetes, SURMOUNT-MMO, is still running.
HFpEF is the form of heart failure most tied to obesity: the heart pumps normally but is stiff, leaving people breathless and exhausted. Nearly 60% of people with HFpEF in the U.S. also have obesity.
Share of people with cardiovascular death or a worsening heart-failure event (hospitalization, urgent visit or a step-up in diuretics). Hazard ratio 0.62, a 38% lower risk.
Heart-failure hospitalizations specifically fell 56% (3.3% versus 7.1%). Symptom scores on the Kansas City Cardiomyopathy Questionnaire improved by about 25 points with tirzepatide versus about 15 with placebo, and weight fell 15.7% versus 2.2%.5 The benefit came from fewer heart-failure events; the trial was too small to say anything about deaths. As covered below, this result has not become a U.S. approval.
In obstructive sleep apnea, the airway repeatedly collapses during sleep, cutting off breathing. It’s measured by the apnea-hypopnea index (AHI), the number of breathing pauses or shallow-breathing episodes per hour. Thirty or more is severe. Excess weight around the neck and upper airway is one of its main causes.
Change in breathing events per hour of sleep, from a starting average of about 50.
Tirzepatide also reduced oxygen drops during sleep, systolic blood pressure and C-reactive protein (a marker of inflammation), and people reported less sleep disturbance.6 In December 2024 it became the first medicine FDA-approved for sleep apnea in adults with obesity. It doesn’t replace CPAP for everyone; the trial in CPAP users shows the two can be used together.
Metabolic dysfunction-associated steatohepatitis, or MASH (formerly NASH), is fat buildup in the liver that has progressed to inflammation and scarring. It’s common with obesity and diabetes and can lead to cirrhosis, liver cancer and transplant.
Share of people whose liver inflammation resolved without the scarring getting worse.
About half of the people on tirzepatide also saw their scarring improve by at least one stage without the inflammation worsening, versus 30% on placebo.7 These are strong numbers, but this was a mid-sized phase 2 trial over one year. Tirzepatide is not approved for MASH. A large phase 3 trial, SYNERGY-Outcomes, is testing whether it prevents cirrhosis and other liver events, with results expected around 2030. Semaglutide is further along here: it received accelerated FDA approval for MASH in 2025 based on a phase 3 trial.
Average change in body weight after three years.
Over three years, tirzepatide lowered the risk of prediabetes progressing to type 2 diabetes by 94% compared with placebo; only 9 of the 762 people on tirzepatide developed diabetes. After treatment stopped, weight began to come back and some people did progress, though risk was still 88% lower than placebo at the end of the off-treatment period.8 Diabetes prevention is not an approved use.
Kidneys. Semaglutide has a completed kidney outcome trial (FLOW) and an approval for kidney disease in type 2 diabetes. Tirzepatide doesn’t yet. Its dedicated kidney study, TREASURE-CKD, is a phase 2 trial, and a phase 3 trial would still be needed before any approval. SURPASS-CVOT reported better kidney measures than dulaglutide, but as a secondary finding.
Psoriasis and psoriatic arthritis. Lilly is testing tirzepatide alongside its psoriasis drug Taltz (ixekizumab) in people who also have obesity. In TOGETHER-PsO, complete skin clearance at 36 weeks was reached by 40.6% of people on the combination versus 29.0% on Taltz alone, and the combined goal of clear skin plus at least 10% weight loss by 27.1% versus 5.8%. The companion psoriatic arthritis trial showed similar advantages, and both held up at one year.9 These were open-label studies of the combination, not evidence that tirzepatide treats psoriasis on its own.
Type 1 diabetes and several smaller investigator-led uses are also in trials, with no results that should guide treatment yet.
The clearest example is heart failure. Despite SUMMIT’s positive result, Lilly withdrew its U.S. application for HFpEF in 2025 after the FDA said one more confirmatory trial was needed. Regulators in other countries reviewed the data separately.11 The same thing happened earlier with semaglutide’s HFpEF application, so this reflects how much evidence the FDA wants for a heart-failure claim rather than a safety concern.
SURPASS-CVOT is the other point to read carefully. Tirzepatide matched an established heart-protective drug but didn’t prove superior to it. Anyone describing it as “better for your heart than” a GLP-1 is going beyond the data.
Two randomized trials have compared tirzepatide directly with semaglutide. These are the only comparisons on this page where the same kind of patients were randomly assigned to one drug or the other.
Average change in body weight.
Waist size fell 18.4 cm with tirzepatide versus 13.0 cm with semaglutide. About a third of people on tirzepatide (31.6%) lost at least a quarter of their body weight, versus 16.1% on semaglutide. Stopping because of side effects was slightly less common with tirzepatide (6.1% versus 8.0%).12
Change in A1C, the three-month average of blood sugar.
Weight fell 11.2 kg with tirzepatide 15 mg versus 5.7 kg with semaglutide.13 One caveat: SURPASS-2 used semaglutide 1 mg, below the 2 mg diabetes dose available today, so it likely understates semaglutide.
For heart, kidney and liver outcomes, no head-to-head trial exists. Comparing those requires putting separate trials side by side, which is what the next table does, with that limitation spelled out.
| Area | Tirzepatide | Semaglutide | How they were compared |
|---|---|---|---|
| Weight (obesity) | −20.2% | −13.7% | Head to head, SURMOUNT-5 |
| A1C (type 2 diabetes) | −2.30 points | −1.86 points (1 mg) | Head to head, SURPASS-2 |
| Heart attack, stroke, CV death | 8% lower vs dulaglutide, in diabetes with heart disease; approved | 20% lower vs placebo, in heart disease without diabetes; approved | Separate trials, different patients and comparators |
| Heart failure (HFpEF) | 38% fewer events; U.S. filing withdrawn | Better symptoms and walking distance | Separate trials |
| Sleep apnea | About 25–29 fewer events per hour; approved | Not approved for sleep apnea | Tirzepatide only |
| Kidneys | Phase 2 trial underway | 24% fewer major kidney events; approved | Semaglutide only |
| Liver (MASH) | Resolved in 62% vs 10% (phase 2) | Resolved in 62.9% vs 34.3% (phase 3); approved | Separate trials |
Semaglutide figures are from our semaglutide article. Placebo response rates, patient groups and trial lengths all differ between separate trials, so similar-looking numbers can’t be read as equal effects, and a bigger number in one trial doesn’t mean a bigger effect.
Every trial above used FDA-approved tirzepatide made by the manufacturer, at 5 to 15 mg weekly. Compounded tirzepatide is prepared by licensed pharmacies for individual prescriptions. It is not FDA-approved and has not been evaluated by the FDA for safety, effectiveness or quality, and none of these trials studied it.
Lower “microdose” regimens are a separate question. There are no published outcome data for sub-therapeutic doses, and none of the results above should be attributed to them.
They apply to the people studied. SURPASS-CVOT enrolled people with diabetes and existing heart disease. SUMMIT enrolled people with heart failure. SURMOUNT-OSA required moderate-to-severe sleep apnea, and SYNERGY-NASH required biopsy-proven liver disease. A result in one of those groups doesn’t automatically carry over to a healthy adult.
The benefits last only while treatment continues. SURMOUNT-4 and the three-year diabetes-prevention data both showed weight and risk returning after the drug stopped.
Side effects are real. Nausea, diarrhea, vomiting and constipation are common, especially while the dose is increasing, and are the most frequent reason people stop. Less common but serious risks include pancreatitis, gallbladder disease, low blood sugar when combined with insulin or sulfonylureas, and kidney injury from dehydration. Tirzepatide can make birth-control pills less reliable after starting and after each dose increase. It carries a boxed warning about thyroid C-cell tumors seen in rodents and shouldn’t be used by people with a personal or family history of medullary thyroid cancer or MEN 2. Only a licensed clinician who knows your history can weigh these for you.
Compare compounded tirzepatide and semaglutide options and start a provider evaluation.
join.ajpeptide.comThe companion article on semaglutide’s heart, kidney, liver and joint trials.
Semaglutide, beyond the scalePrescription required. Provider evaluation at no charge. A licensed clinician determines eligibility, dosing and monitoring for every patient. Individual results vary. This article is for education and is not medical advice. Mounjaro, Zepbound, Trulicity and Taltz are registered trademarks of Eli Lilly and Company; Wegovy and Ozempic are registered trademarks of Novo Nordisk A/S. AJ Peptide is not affiliated with either company.
