Semaglutide and tirzepatide copy gut hormones that tell your brain you're full. In big trials people lost 15 to 21% of their body weight, and the benefits reach the heart, kidneys, liver and sleep. But most of the weight returns if you stop, and part of what's lost is muscle.
Strong evidenceUpdated Oct 2026 · 4 new studiesGLP-1 is a hormone your gut releases after eating. It slows stomach emptying, helps the pancreas release insulin when blood sugar is high, and acts on appetite centres in the brain. Your own GLP-1 is broken down within minutes; semaglutide (Wegovy, Ozempic) is built to last a week.
Tirzepatide (Mounjaro, Zepbound) also mimics a second gut hormone, GIP, and is a little more powerful. Pills are arriving: oral semaglutide 25 mg was approved for weight loss in the US in December 2025, and orforglipron is a non-peptide pill in late trials. Retatrutide adds a third hormone, glucagon, and has produced the largest weight losses yet.
The benefits go beyond the scale: fewer heart attacks and strokes (SELECT), slower kidney decline in diabetes (FLOW), healing of fatty liver inflammation (MASH) and less sleep apnoea. The costs: nausea and other gut effects are common, a quarter or more of the weight lost can be lean tissue, and weight comes back after stopping, so for most people these are long-term medicines.
Your gut releases GLP-1 after a meal, but an enzyme breaks it down within about 2 minutes. Semaglutide is built to resist that enzyme and stick to blood proteins, so one weekly dose keeps levels steady. Illustration, not to scale.
The drug acts like your own GLP-1 but lasts for days instead of minutes.
Appetite centres quieten, so food 'noise' and cravings drop.
Food leaves the stomach more slowly, so you feel full for longer.
Blood sugar, blood pressure and liver fat improve along with weight.
In trials, average loss was about 15% with semaglutide 2.4 mg (STEP 1) and 21% with tirzepatide 15 mg (SURMOUNT-1) after 68 to 72 weeks.
2,539 adults with obesity, 72 weeks
Weekly tirzepatide cut body weight by 15% to 20.9% depending on dose, versus 3.1% on placebo. On the top dose, 57% of people lost at least a fifth of their weight.
Read the source ↗17,604 adults with heart disease and overweight, no diabetes
Semaglutide cut heart attacks, strokes and heart deaths by 20%: 6.5% versus 8.0% over about 3 years. Industry funded.
Read the source ↗3,533 people with type 2 diabetes and kidney disease
Semaglutide lowered the risk of major kidney events by 24% and death from any cause by 20% over a median 3.4 years. The trial stopped early for benefit.
Read the source ↗327 adults followed after stopping
People who lost 17.3% of their weight on semaglutide regained 11.6 percentage points, about two-thirds, in the year after stopping. Blood pressure and blood sugar gains also faded.
Read the source ↗469 adults with obesity and sleep apnoea
Tirzepatide cut breathing pauses by 25 to 29 events an hour versus about 5 on placebo over a year, alongside 16 to 17% more weight loss.
Read the source ↗800 adults with fatty liver inflammation (MASH) and scarring
After 72 weeks, liver inflammation cleared in 62.9% on semaglutide versus 34.3% on placebo, and scarring improved in 36.8% versus 22.4%. Long-term outcomes are still being followed.
Read the source ↗The first GLP-1 weight-loss pills have arrived, and a triple-hormone injection, retatrutide, produced around a quarter of body weight lost. But semaglutide failed to slow Alzheimer's disease in two large trials, and the alcohol findings are still early.
Every study added to this page since January 2025. Green rings are the strongest evidence: large trials or meta-analyses.
Wharton et al. (ATTAIN-1), 2025, 3,127 adults without diabetes. Average weight lost after 72 weeks on orforglipron or placebo.
3,127 adults with obesity, no diabetes, 72 weeks
Orforglipron, a once-daily pill that needs no injection or fasting, cut body weight by 11.2% on the top dose versus 2.1% on placebo. That's less than injectable tirzepatide. Industry funded.
3,808 adults aged 55 to 85 with early Alzheimer's, 2 years
Oral semaglutide did not slow memory and thinking decline compared with placebo, despite small shifts in some blood markers. Results were first announced in Nov 2025 and published in full in 2026.
2,339 adults with obesity or overweight, 80 weeks
Retatrutide, a weekly injection that acts on three hormone pathways, cut weight by 19% to 28% depending on dose over 80 weeks. 11.3% on the top dose stopped because of side effects. Company-reported results; full peer-reviewed paper and approval still to come.
48 adults with alcohol use disorder, 9 weeks
Low-dose semaglutide reduced alcohol cravings, the amount drunk in a lab test and drinks per drinking day. Total drinking days did not change. Small and short, so larger trials are needed.
If you take one of these medicines, treat it like blood pressure treatment: the benefit lasts while you take it. Pair it with strength training and protein to protect muscle. A pill may suit people who dislike injections, but expect a little less weight loss, and don't take any of them hoping to prevent dementia.
The drug does the appetite part. Muscle, habits and a long-term plan are up to you.
Strength training helps make sure the weight you lose is mostly fat, not muscle.
Smaller appetites make it easy to undereat protein. Put it first on the plate.
Eating slowly and stopping when full eases nausea. Drink enough to avoid dehydration.
Benefits last while you take the drug. Plan dose and duration with your prescriber.
Online and compounded versions can have the wrong dose or ingredients. Use licensed products from a pharmacy.
Daily activity, fibre-rich food and good sleep are what hold weight off if you ever stop.
✕ MythIt's just a weight-loss jab.
✓ FactSemaglutide also cut heart attacks, strokes and heart deaths by 20% in SELECT and slowed kidney disease in people with diabetes.
✕ MythOnce you reach your goal you can stop and keep the weight off.
✓ FactOn average about two-thirds of the lost weight came back within a year of stopping semaglutide.
✕ MythAll the weight you lose is fat.
✓ FactA quarter or more can be lean tissue, including muscle. Strength training and protein help protect it.
✕ MythGLP-1 drugs protect against Alzheimer's disease.
✓ FactTwo large trials of semaglutide in early Alzheimer's (EVOKE) found no slowing of decline.
In the US, mass compounding was allowed only during shortages, which the FDA declared over in December 2024 (tirzepatide) and February 2025 (semaglutide). Unregulated products may contain the wrong dose or other substances. Use licensed medicines.
A small 9-week trial in 48 adults found semaglutide reduced cravings and some measures of drinking. It's promising but not yet an approved treatment.
Rare risks include pancreatitis, gallstones and, very rarely, sudden optic nerve damage (NAION, up to 1 in 10,000 users per the EMA). They're not advised in pregnancy or with a family history of medullary thyroid cancer.
Read each claim and pick an answer: the card flips to show the verdict and why. Not sure? Use “Just reveal”.
Semaglutide lowers heart attack and stroke risk in people with heart disease and overweight, even without diabetes.
Semaglutide lowers heart attack and stroke risk in people with heart disease and overweight, even without diabetes.
In the SELECT trial of 17,604 adults, major heart events fell by 20% (6.5% vs 8.0%).
Most people keep the weight off after stopping GLP-1 injections.
Most people keep the weight off after stopping GLP-1 injections.
In the STEP 1 extension, people regained about two-thirds of the weight they'd lost within a year of stopping semaglutide.
All the weight you lose on GLP-1 drugs is fat.
All the weight you lose on GLP-1 drugs is fat.
Most is fat, but a quarter or more can be lean tissue. Strength training and enough protein help protect muscle.
Semaglutide slows Alzheimer's disease.
Semaglutide slows Alzheimer's disease.
Two large trials (EVOKE and EVOKE+, 3,808 people) found no slowing of decline compared with placebo.
Tirzepatide can improve obstructive sleep apnoea.
Tirzepatide can improve obstructive sleep apnoea.
In SURMOUNT-OSA, breathing pauses fell by 25 to 29 an hour versus about 5 on placebo.
GLP-1 medicines treat alcohol problems.
GLP-1 medicines treat alcohol problems.
A small 2025 trial found less craving and lower drinking on some measures, but it's not yet a proven or approved treatment.
There's now a GLP-1 pill for weight loss.
There's now a GLP-1 pill for weight loss.
Oral semaglutide was approved in the US in December 2025 after a trial showing 13.6% weight loss versus 2.2% on placebo.
Nausea is the most common side effect.
Nausea is the most common side effect.
Gut effects such as nausea, diarrhoea and constipation are common, especially when the dose is increased, and usually ease over time.
Compounded semaglutide is the same as the brand-name drug.
Compounded semaglutide is the same as the brand-name drug.
Compounded versions aren't approved or checked the same way, and the FDA has warned about products sold online with unverified contents.
Semaglutide can heal inflammation in fatty liver disease.
Semaglutide can heal inflammation in fatty liver disease.
In the ESSENCE trial, liver inflammation cleared in 62.9% on semaglutide versus 34.3% on placebo after 72 weeks.
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