Semaglutide dosage and evidence

What is Semaglutide?

How does Semaglutide work?

It switches on the GLP-1 receptor, a switch on cells that normally answers a gut hormone after you eat. That makes the body release insulin when blood sugar is high. It holds back glucagon, a hormone that raises blood sugar. It slows how fast the stomach empties. It also acts on the part of the brain that runs hunger, so people eat less.

What have studies in people found about Semaglutide?

Semaglutide has a huge record of human trials. Four big trials tracked heart attacks, strokes, kidney failure and deaths in 34,084 people. The weight-loss trials added several thousand more. The maker also published the trials that failed. Two Alzheimer's trials in 3,808 people found the pill did not slow memory loss.

• Heart trial in people without diabetes: 17,604 adults who already had heart disease and a body mass index of 27 or more were followed for about 39.8 months. Heart attacks, strokes and heart deaths hit 6.5% of the drug group and 8.0% of the dummy-shot group.
• Pill heart trial in type 2 diabetes: 9,650 people at high risk took a daily 14 mg pill or a dummy pill for about 47.5 months. Heart attacks, strokes and heart deaths hit 12.0% on the pill and 13.8% on the dummy. The kidney results and the other follow-up checks came out about the same in both groups.
• Alzheimer's: two trials gave the pill to 3,808 people with early Alzheimer's, confirmed by tests for the protein build-up, at 566 sites. After 104 weeks it did not slow their decline. Both trials were stopped because the drug did not work.
• Kidney trial: 3,533 people with type 2 diabetes and kidney disease. Major kidney problems hit 331 people on the drug and 410 on the dummy shot. Fewer people died of any cause on the drug too. The trial was stopped early, at a planned check, because the benefit was already clear.
• Heart safety in type 2 diabetes: 3,297 people were followed for 104 weeks. Heart attacks, strokes and heart deaths hit 6.6% on the drug and 8.9% on the dummy shot. Eye damage from diabetes went the other way: serious problems hit 3.0% on the drug and 1.8% on the dummy.
• Weight loss without diabetes: 1,961 adults on the 2.4 mg weekly shot lost 14.9% of their body weight in 68 weeks. People on the dummy shot lost 2.4%. 86.4% of the drug group lost at least 5%.
• A higher dose: 1,407 adults were tested on 7.2 mg. After 72 weeks they had lost 18.7%, against 15.6% on the usual 2.4 mg and 3.9% on a dummy shot. 22.9% on 7.2 mg had odd skin sensations.
• Weight loss with type 2 diabetes: 1,210 adults lost 9.6% on 2.4 mg over 68 weeks, against 3.4% on a dummy shot, a gap of 6.2 points. Stomach and gut side effects hit 63.5% on the drug and 34.3% on the dummy.
• Fatty liver disease with inflammation and scarring (called MASH): liver samples were checked at 72 weeks in the first 800 of 1,197 patients. The inflammation cleared, without the scarring getting worse, in 62.9% on the drug and 34.3% on the dummy shot. Scarring improved in 36.8% against 22.4%. Weight fell 10.5% against 2.0%. Pain scores did not differ. This is a look taken partway through the trial.
• Stopping the drug: 902 people spent 20 weeks building up to the full dose and lost 10.6% on average. The 803 who reached 2.4 mg were then split: two thirds kept going and one third switched to a dummy shot. From week 20 to week 68, those who kept going lost another 7.9%. Those who switched gained back 6.9%. That is a gap of 14.8 points, from stopping alone.
• Clogged leg arteries: 792 people with type 2 diabetes and leg artery disease took 1.0 mg or a dummy shot for 52 weeks. The furthest they could walk on a treadmill rose by a ratio of 1.21 on the drug and 1.08 on the dummy. That leaves the drug about 13% ahead.
• A year after stopping: 327 people were followed after all treatment ended. They had lost 17.3% by week 68. By week 120 they had regained 11.6 points of that, leaving them 5.6% lighter than at the start. Most gains in blood pressure, blood sugar and blood fats drifted back toward where they started.
• Pill for weight loss: 307 adults took a daily 25 mg pill or a dummy pill. After 64 weeks they had lost 13.6%, against 2.2%. Stomach and gut side effects hit 74.0% against 42.2%.

What this does not tell you: No trial has run longer than about four years, so nobody knows what happens after that. The big heart and kidney trials only took people who were already sick with heart disease, diabetes or kidney disease. They do not tell a healthy adult in their forties what to expect, and nobody has tested that. Two trials show the weight comes back when people stop. So the weight-loss numbers describe people still taking the drug. None of these trials was built mainly to measure body fat, bone strength or muscle. And every number here came from the maker's own product, started low and raised step by step. A vial from a compounding pharmacy or a 'research' seller is not the same thing.

What do people who took Semaglutide report?

This is what real people say happened to them, good and bad. Nobody measured it. A report cannot tell a real effect from the lift people get just from expecting it to work, from a diet or training change made at the same time, or from what was really in the vial. We still put it near the top. It is the next best thing to a study in people: what happens when real people use it, including what goes wrong.

• As with tirzepatide, a large share of discussion is simply people working out that two differently branded products are the same molecule approved for different things at very different prices, and that a third similar drug is a different molecule again.
• The effect people describe valuing most is appetite and food preoccupation falling away rather than the number on the scale, and it is frequently described in terms of no longer having to spend attention on food.
• Direct comparison against tirzepatide is constant and goes both ways. A recurring pattern is people describing themselves as doing better on one than the other with no clear reason, and switching between them.
• Low mood and blunted enjoyment are raised as a specific negative by some users, who describe it as a distinct effect rather than an unrelated coincidence, and other users regularly point them toward discussing it with a clinician. It is also described as taking a couple of weeks to clear after stopping.
• The end of compounded availability in the United States is a major practical topic, with people describing losing access, facing the branded price without insurance, or having been on a compounded product without being sure what it was.
• There is a persistent undercurrent of resentment about how much of the public conversation is celebrity and advertising rather than people managing a condition, and in bodybuilding contexts a minority frame it as one component among several rather than a treatment.

Sources: Public discussion in r/Semaglutide, r/Zepbound, r/glp1 and general subreddits where GLP-1 drugs come up, read through the PullPush Reddit archive on 2026-09-13 because Reddit's own endpoints are unreachable from this environment. 62 comments reviewed. Nothing above is attributed to any specific post and no comment is reproduced.

The state of the research

The evidence, in charts

The studies we cite

• Study in people2023
  Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)

  This is about as strong as evidence for a drug gets. Everyone taking part already had heart disease and carried extra weight, and none of them had diabetes. Half were given semaglutide, half a dummy injection, and everyone was followed for a bit over three years. Heart attacks, strokes and deaths from heart disease fell by a fifth. In plain counts that is about 15 fewer of those events for every 1,000 people treated.

  17,604 adults with cardiovascular disease and BMI 27 or higher but no diabetes: semaglutide 2.4 mg cut major adverse cardiovascular events 20% (6.5% vs 8.0%; HR 0.80) over a mean 39.8 months.

  PMID 37952131 New England Journal of Medicine
• Study in people2021
  Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)

  It worked, and this is the trial that made semaglutide famous for weight loss. Nearly two thousand adults without diabetes took a weekly shot of either semaglutide or a dummy version for about sixteen months. Nobody involved knew which. The semaglutide group finished roughly 15% lighter. The dummy group finished roughly 2% lighter. Almost nine in ten people on the drug lost at least 5% of the weight they started with.

  1,961 adults without diabetes: mean body weight change of -14.9% at 68 weeks with semaglutide 2.4 mg versus -2.4% with placebo; 86.4% lost 5% or more.

  PMID 33567185 New England Journal of Medicine
• Study in people2026
  Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials

  Semaglutide was tested properly in Alzheimer's disease and it did not work. Nearly four thousand people whose early Alzheimer's had been confirmed by an amyloid test took a daily semaglutide pill or a dummy pill for two years. Nobody involved knew which. Memory and daily function slipped at the same rate in both groups. Both trials were stopped and written up as negative. A test this large would have found a real benefit if there was one.

  3,808 participants with amyloid-confirmed early Alzheimer's disease across 566 sites: oral semaglutide did not slow decline on the CDR-SB primary endpoint at week 104 and both trials were discontinued for negative clinical outcome.

  PMID 41865758 The Lancet
• Study in people2025
  Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity (OASIS 4)

  The pill version works too, and this was a small trial. Just over three hundred adults carrying extra weight were split so two in every three got a 25 mg semaglutide tablet and the rest got a dummy tablet. After about fifteen months the tablet group was roughly 14% lighter and the dummy group roughly 2% lighter. Stomach trouble was common. Nausea, vomiting or diarrhoea hit about three quarters of the tablet group against about four in ten on the dummy.

  307 adults randomized 2:1: oral semaglutide 25 mg produced -13.6% body weight at week 64 versus -2.2% with placebo (treatment-policy estimand); GI adverse events in 74.0% vs 42.2%.

  PMID 40934115 New England Journal of Medicine
• Study in people2025
  Once-weekly semaglutide 7.2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial

  A bigger weekly dose took off a little more weight, and cost more side effects. Just over 1,400 adults with obesity took semaglutide at 7.2 mg, semaglutide at the usual 2.4 mg, or a dummy injection for about seventeen months. The high dose group finished roughly 19% lighter, the usual dose roughly 16% lighter, and the dummy group roughly 4% lighter. About one in five on the high dose reported burning or prickling skin sensations.

  1,407 adults: -18.7% body weight at 72 weeks on 7.2 mg versus -15.6% on 2.4 mg and -3.9% on placebo; dysaesthesia reported by 22.9% on 7.2 mg.

  PMID 40961952 The Lancet Diabetes & Endocrinology
• Study in people2021
  Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial

  Semaglutide still worked when people also had diabetes, though the weight loss was smaller. About 1,200 adults with extra weight and type 2 diabetes got the weekly shot or a dummy one, and nobody involved knew which. After 68 weeks the drug group had lost about a tenth of their body weight and the dummy group about 3%. Roughly seven in ten on the drug lost at least 5% of their weight, against under three in ten.

  1,210 adults with overweight or obesity and type 2 diabetes: estimated body weight change -9.6% on semaglutide 2.4 mg versus -3.4% on placebo at 68 weeks; 68.8% versus 28.5% lost at least 5%.

  PMID 33667417 The Lancet
• Study in people2021
  Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial

  Stop the drug and the weight comes back. Everyone spent 20 weeks building up to the full dose and losing weight first. Then 803 people were split by chance: two thirds carried on with semaglutide, one third switched to a dummy shot. Over the next 48 weeks the people who kept taking it lost another 7.9% of their weight. The people who switched gained 6.9% back. That is a gap of nearly 15 percentage points, from stopping alone.

  803 participants randomized 2:1 after a 20-week run-in: weight change from week 20 to 68 was -7.9% on continued semaglutide versus +6.9% after switching to placebo, a difference of 14.8 percentage points.

  PMID 33755728 JAMA
• Study in people2022
  Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension

  A year after everyone stopped, most of the weight had come back. 327 people from the original trial were weighed again a year after all treatment ended. They had lost 17.3% of their body weight on semaglutide and put 11.6 points of that back, leaving about 5.6% off. Blood pressure, blood sugar and blood fats drifted back towards where they started. These figures describe what happens when the drug stops, not a lasting change.

  327 participants followed for a year after treatment stopped: the semaglutide group regained 11.6 of the 17.3 percentage points lost, leaving a net 5.6% at week 120, with cardiometabolic measures reverting towards baseline.

  PMID 35441470 Diabetes, Obesity and Metabolism
• Study in people2016
  Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

  Semaglutide cut heart attacks and strokes in people with diabetes, and it made eye damage worse. 3,297 people were followed for two years on the drug or a dummy shot. Heart attacks, strokes and deaths from heart disease hit 6.6% of the drug group and 8.9% of the dummy group, about 23 fewer such events for every 1,000 people. Serious retinopathy, the diabetic eye disease, went the other way: 3.0% against 1.8%. That harm is real and was not explained away.

  SUSTAIN-6, 3,297 patients over 104 weeks: primary composite in 6.6% versus 8.9% (HR 0.74), but retinopathy complications were significantly higher on semaglutide (HR 1.76, 95% CI 1.11 to 2.78).

  PMID 27633186 New England Journal of Medicine
• Study in people2024
  Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes

  Semaglutide protected the kidneys well enough that the trial was stopped early. 3,533 people with type 2 diabetes and kidney disease got the drug or a dummy shot, and nobody involved knew which. Major kidney events, meaning kidney failure, a large drop in kidney function or death from kidney or heart causes, hit 331 on the drug and 410 on the dummy. Fewer people died of any cause as well. Independent monitors halted it because the benefit was already clear.

  FLOW, 3,533 participants, stopped early at interim analysis: major kidney disease events 331 versus 410 (HR 0.76, 95% CI 0.66 to 0.88) and all-cause death HR 0.80 over a median 3.4 years.

  PMID 38785209 New England Journal of Medicine
• Study in people2025
  Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes

  The pill form of semaglutide also cut heart attacks and strokes, by a modest amount. 9,650 people with type 2 diabetes at high risk took a daily 14 mg tablet or a dummy tablet for about four years. Heart attacks, strokes and cardiac deaths hit 12.0% on the drug and 13.8% on the dummy, about 18 fewer such events for every 1,000 people. The kidney and other follow-up measures came out the same in both groups, so this result rests on the heart numbers alone.

  SOUL, 9,650 participants over a mean 47.5 months: major adverse cardiovascular events in 12.0% versus 13.8% (HR 0.86). The confirmatory secondary outcomes, including the kidney composite, did not differ significantly.

  PMID 40162642 New England Journal of Medicine
• Study in people2025
  Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis

  Semaglutide healed liver inflammation in a serious fatty liver disease, on a look taken partway through. Liver samples were taken from the first 800 of 1,197 patients at 72 weeks. The inflammation cleared without the scarring getting worse in 62.9% on the drug against 34.3% on the dummy, and scarring improved in 36.8% against 22.4%. Bodily pain scores were no different. This is a look taken partway through, so the full trial has not reported yet.

  ESSENCE interim analysis at week 72 in the first 800 of 1,197 patients with biopsy-defined MASH: steatohepatitis resolution in 62.9% versus 34.3% and fibrosis improvement in 36.8% versus 22.4%. Bodily pain scores did not differ.

  PMID 40305708 New England Journal of Medicine
• Study in people2025
  Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial

  People with clogged leg arteries walked further on semaglutide, and the gain was small. 792 people with type 2 diabetes and leg artery disease took the drug or a dummy shot for a year. The furthest they could walk on a treadmill rose by about a fifth on the drug and about a twelfth on the dummy. That leaves roughly a 13% edge for semaglutide. It is a real difference, measured on a treadmill rather than in daily life.

  792 participants over 52 weeks: median ratio to baseline maximum walking distance 1.21 versus 1.08, an estimated treatment ratio of 1.13 (95% CI 1.06 to 1.21).

  PMID 40169145 The Lancet
• Study in people2024
  Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide

  A single eye clinic reported far more cases of a sudden blinding optic nerve stroke among its semaglutide patients. Nobody was given anything. Researchers looked back through records at one specialist clinic for eye nerve problems, covering 16,827 patients. Over three years the condition appeared in 8.9% of semaglutide patients with diabetes against 1.8% of others, and 6.7% against 0.8% among those treated for weight. This clinic has such cases referred to it, so its patients are not typical, and it cannot show the drug caused this.

  Retrospective matched cohort at one neuro-ophthalmology practice, 16,827 patients screened: 36-month cumulative NAION incidence 8.9% versus 1.8% in type 2 diabetes (HR 4.28) and 6.7% versus 0.8% in overweight or obesity (HR 7.64). Observational, referral population, causality not established.

  PMID 38958939 JAMA Ophthalmology
• Study in people2025
  Association between Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Study

  A much larger records study found no sign of that eye problem. Nobody was given anything here either. Researchers matched 297,220 people across 160 health systems in 21 countries and compared those on semaglutide with those on other diabetes drugs. At one, two and three years there was no clear link in any group. The range around that answer was wide enough to include both harm and benefit, so it does not rule the risk out. The two studies still disagree.

  Propensity-matched cohorts from 160 health care organisations in 21 countries totalling 297,220 participants: no significant association with NAION at one, two or three years in any subgroup, with confidence intervals wide enough to include both harm and benefit.

  PMID 39491755 Ophthalmology