SEMAGLUTIDE
Semaglutide is a GLP-1 receptor agonist used in approved medicines for type 2 diabetes and chronic weight management. It works partly by reducing appetite and helping people feel fuller, and has been studied extensively in large human clinical trials.
SEMAGLUTIDE — QUICK SUMMARY
What is Semaglutide?
Semaglutide is a medicine that mimics GLP-1, a hormone released naturally after eating. GLP-1 is involved in appetite, digestion and blood-sugar control, helping signal that food has been eaten and influencing how the body responds to a meal.
One of semaglutide’s most noticeable effects is on appetite. GLP-1 signalling in the brain can reduce hunger and increase feelings of fullness, making it easier for some people to eat less. Semaglutide can also slow the movement of food through the stomach and helps the pancreas release insulin when blood glucose is elevated.
Semaglutide has been developed into several prescription medicines. In Australia, Ozempic is approved for type 2 diabetes, while Wegovy is approved for chronic weight management in eligible people. The active drug is semaglutide, but the approved uses and treatment regimens differ between products.
Its effects on body weight have been studied in large human trials. In the STEP 1 trial, 1,961 adults with overweight or obesity were followed for 68 weeks. Participants assigned to 2.4 mg semaglutide once weekly lost an average of 14.9% of their starting body weight, compared with 2.4% in the placebo group, alongside lifestyle intervention.
Semaglutide is the active ingredient, not a single brand. Ozempic and Wegovy both contain semaglutide, but they are approved for different primary uses and use different treatment regimens. Evidence or dosing associated with one product should not automatically be assumed to apply identically to the other.
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Semaglutide Research & Evidence
What human research tells us about weight loss, appetite, blood sugar, cardiovascular health and the other major areas in which Semaglutide has been studied.
Weight Loss
Weight management has one of the strongest human evidence bases for Semaglutide.
In the STEP 1 trial, 1,961 adults with overweight or obesity but without diabetes received either weekly Semaglutide 2.4 mg or placebo alongside lifestyle intervention for 68 weeks.
Average body weight fell by 14.9% with Semaglutide compared with 2.4% with placebo. In absolute terms, the average change was 15.3 kg versus 2.6 kg.
Around 50.5% of participants receiving Semaglutide lost at least 15% of their starting weight, compared with 4.9% receiving placebo.
Appetite & Eating Behaviour
Semaglutide acts on GLP-1 receptors involved in appetite regulation. In practical terms, this can reduce hunger, increase fullness and make smaller amounts of food feel more satisfying.
In a STEP 5 eating-behaviour analysis, people receiving Semaglutide reported better control of eating and reduced food cravings compared with placebo during long-term treatment.
These appetite effects help explain why weight loss can be substantial even though Semaglutide is not a stimulant or traditional appetite suppressant.
Appetite responses still vary considerably between individuals, and not everyone experiences the same degree of hunger reduction.
Blood Sugar
Semaglutide was originally developed as a treatment for type 2 diabetes and has extensive human evidence for improving blood glucose control.
In the SUSTAIN 1 trial, 388 adults with type 2 diabetes were studied for 30 weeks. Average HbA1c fell by about 1.45 percentage points with 0.5 mg weekly and 1.55 points with 1.0 mg, compared with almost no change with placebo.
Semaglutide helps the pancreas release more insulin when blood glucose is elevated and reduces glucagon, another hormone that can raise blood sugar.
This glucose-lowering evidence applies primarily to people with type 2 diabetes rather than healthy people with normal glucose regulation.
Cardiovascular Outcomes
Large outcome trials show that Semaglutide can reduce major cardiovascular events in people already at high cardiovascular risk.
The SELECT trial included 17,604 adults with overweight or obesity and established cardiovascular disease but without diabetes.
Over about 40 months, cardiovascular death, non-fatal heart attack or non-fatal stroke occurred in 6.5% of the Semaglutide group and 8.0% of the placebo group.
That corresponds to a 20% relative reduction in the risk of the trial's major cardiovascular endpoint. This does not mean every person experiences the same benefit; the trial involved people with established cardiovascular disease.
Kidney Outcomes
Semaglutide has also been studied directly in people with type 2 diabetes and chronic kidney disease.
In the FLOW trial, 3,533 participants were followed for a median of 3.4 years.
The risk of the primary kidney-related outcome was 24% lower with Semaglutide than placebo. The trial also found a slower average decline in kidney filtration and fewer cardiovascular deaths.
These findings apply to people with established type 2 diabetes and chronic kidney disease. They should not be interpreted as evidence that Semaglutide improves kidney function in otherwise healthy people.
Side Effects & Tolerability
Gastrointestinal effects are the most consistent adverse events reported across Semaglutide trials.
In STEP 1, nausea and diarrhoea were common, and 4.5% of participants receiving Semaglutide stopped treatment because of gastrointestinal effects compared with 0.8% receiving placebo.
In the two-year STEP 5 trial, gastrointestinal adverse events were reported in 82.2% of the Semaglutide group and 53.9% of the placebo group. Most were classified as mild to moderate.
The overall evidence therefore supports meaningful benefits, but tolerability can be an important practical limitation.
Semaglutide has a strong human evidence base, including large randomised controlled trials and long-term cardiovascular and kidney outcome studies. Evidence is particularly strong for weight management and type 2 diabetes, with additional outcome data supporting cardiovascular and kidney benefits in specific high-risk populations. The size of benefit varies by population, dose, treatment duration and outcome being measured.
Semaglutide Questions & Answers
In the major STEP 1 trial, adults with overweight or obesity who did not have diabetes lost an average of 14.9% of their starting body weight over 68 weeks with weekly Semaglutide 2.4 mg.
The placebo group lost 2.4% over the same period. Average absolute weight loss was approximately 15.3 kg with Semaglutide versus 2.6 kg with placebo.
Individual responses varied considerably, so these averages should not be treated as a guaranteed result.
Appetite regulation is a major part of its effect, but not the whole story.
Semaglutide mimics GLP-1 signalling in areas of the brain involved in hunger and fullness. It can reduce hunger, increase satiety and change eating behaviour.
It also affects blood glucose regulation and slows stomach emptying, particularly earlier in treatment. These effects together can reduce food intake.
Semaglutide is the active drug contained in both Ozempic and Wegovy.
They are not identical products, however. They are approved for different primary uses and use different treatment regimens.
This distinction matters when interpreting trials because research using one formulation or dose should not automatically be treated as evidence for every Semaglutide product.
Human research suggests that some weight regain is common after treatment stops.
In the STEP 1 extension, participants who had received Semaglutide regained a substantial proportion of the weight they had lost during the following year after treatment was withdrawn.
This supports the view that obesity is generally a chronic condition and that the biological pressures affecting appetite and weight can return when treatment is removed.
Yes, in specific high-risk populations.
In SELECT, 17,604 people with overweight or obesity and established cardiovascular disease but no diabetes had a 20% lower relative risk of cardiovascular death, non-fatal heart attack or non-fatal stroke with Semaglutide than placebo.
This does not mean Semaglutide has been proven to prevent cardiovascular disease in every healthy person. The people studied already had cardiovascular disease.
Gastrointestinal effects are the most consistently reported.
Nausea, diarrhoea, vomiting and constipation occur more often with Semaglutide than placebo. In large obesity trials, these effects were usually described as mild to moderate and often improved over time.
A minority of participants stopped treatment because of gastrointestinal symptoms, so tolerability is still an important part of the evidence.
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Medical Literature
Important human Semaglutide studies covering weight management, diabetes, cardiovascular outcomes, kidney disease and long-term treatment.
Effect of Semaglutide on Kidney Outcomes in SELECT, FLOW and SOUL
This prespecified analysis pooled participant-level data from 30,787 people across three large randomised trials.
Major kidney outcomes occurred less often with Semaglutide than placebo, with a hazard ratio of 0.84. The analysis included people with cardiovascular disease, chronic kidney disease and type 2 diabetes across different Semaglutide formulations.
View Study →Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes
The SOUL trial included 9,650 people with type 2 diabetes plus cardiovascular disease, chronic kidney disease or both.
Major cardiovascular events occurred in 12.0% of participants receiving oral Semaglutide and 13.8% receiving placebo, corresponding to a hazard ratio of 0.86.
View Study →Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes
FLOW enrolled 3,533 participants with type 2 diabetes and chronic kidney disease and followed them for a median of 3.4 years.
Semaglutide reduced the risk of the primary kidney outcome by 24% compared with placebo and also slowed the average decline in kidney filtration.
View Study →Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
SELECT studied 17,604 adults with overweight or obesity and established cardiovascular disease but without diabetes.
Major cardiovascular events occurred in 6.5% of the Semaglutide group and 8.0% of the placebo group, representing a 20% relative risk reduction.
View Study →Long-Term Weight Loss Effects of Semaglutide in the SELECT Trial
In SELECT, Semaglutide-associated weight loss continued for around 65 weeks and was then sustained for up to four years.
At week 208, average body weight was 10.2% below baseline with Semaglutide compared with 1.5% below baseline with placebo.
View Study →Two-Year Effects of Semaglutide in Adults with Overweight or Obesity
STEP 5 followed 304 adults for 104 weeks.
Average body weight fell by 15.2% with Semaglutide compared with 2.6% with placebo. Gastrointestinal adverse events occurred more often with Semaglutide.
View Study →Weight Regain after Withdrawal of Semaglutide
This STEP 1 extension followed 327 participants for a year after treatment was stopped.
Participants who had received Semaglutide regained a substantial proportion of their previous weight loss after withdrawal, showing that much of the weight-management effect depends on continued treatment.
View Study →Once-Weekly Semaglutide in Adults with Overweight or Obesity
STEP 1 randomised 1,961 adults without diabetes to weekly Semaglutide 2.4 mg or placebo for 68 weeks alongside lifestyle intervention.
Average body weight fell by 14.9% with Semaglutide and 2.4% with placebo. Around half of Semaglutide-treated participants lost at least 15% of their starting weight.
View Study →Continued Semaglutide versus Withdrawal for Weight Maintenance
STEP 4 examined what happened after a 20-week Semaglutide run-in period when participants either continued treatment or were switched to placebo.
People who continued Semaglutide kept losing weight, while those switched to placebo regained weight, supporting the importance of ongoing treatment for weight maintenance.
View Study →Semaglutide Monotherapy in Type 2 Diabetes — SUSTAIN 1
SUSTAIN 1 studied 388 treatment-naive adults with type 2 diabetes for 30 weeks.
HbA1c fell by about 1.45 percentage points with 0.5 mg weekly and 1.55 points with 1.0 mg, while placebo produced almost no change. Body weight also fell more with Semaglutide.
View Study →Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
SUSTAIN 6 studied people with type 2 diabetes who were already at high cardiovascular risk.
Major cardiovascular events occurred less often with Semaglutide than placebo, producing a hazard ratio of 0.74 for cardiovascular death, non-fatal heart attack or non-fatal stroke.
View Study →Semaglutide has an unusually large human evidence base compared with many compounds discussed on Supp Science. However, findings still depend heavily on who was studied. Weight-loss trials generally involved people with overweight or obesity, diabetes trials involved people with type 2 diabetes, and cardiovascular or kidney outcome trials focused on people already at elevated medical risk. Results from these populations should not be assumed to apply identically to healthy people.
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