MVIIIHealth The MVIII app
← Back

Research · Medication

Semaglutide

In STEP 1, weekly semaglutide 2.4 mg cut body weight 14.9% over 68 weeks against 2.4% on placebo. In SELECT it lowered major cardiovascular events by 20% in people with heart disease. A year after stopping, two-thirds of the lost weight returned. Gastrointestinal effects and gallbladder disease rose, and lean mass fell with the weight.

Add to Bio HackChecked 2026-11-13
Status
Prescription drug in the US. FDA-approved as Ozempic (weekly injection) for type 2 diabetes, to reduce cardiovascular risk in type 2 diabetes with cardiovascular disease, and to reduce the risk of sustained kidney function decline, end-stage kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. Rybelsus (daily tablet) is approved for type 2 diabetes. Wegovy (weekly injection) is approved for chronic weight management, to reduce cardiovascular risk in adults with cardiovascular disease and obesity or overweight, and, under accelerated approval that depends on a confirmatory trial, for noncirrhotic MASH with moderate to advanced liver fibrosis (stages F2 to F3) in adults. A 7.2 mg weekly Wegovy injection (Wegovy HD) is approved as the maximum weight reduction dose for adults who have tolerated 2.4 mg for at least 4 weeks when additional weight reduction is clinically indicated. A Wegovy tablet is approved for weight management and cardiovascular risk.
Also called
Ozempic, Wegovy, Wegovy HD, Rybelsus, GLP-1, GLP-1 receptor agonist, sema, semaglutide 7.2 mg
Taken for
weight loss, fat loss, appetite, heart health, keeping weight off, kidney disease, fatty liver, MASH

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help6

Reported risks8

What people take it for, and what was found

Shown to help6

ModerateVery common

Weight loss

Shown to lower body weight about 12.7 kg more than placebo over 68 weeks in adults with obesity without diabetes. Tirzepatide lowered weight more head to head.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
At 68 weeks, body weight changed by -14.9% on semaglutide and -2.4% on placebo, a difference of -12.4 percentage points (95% CI -13.4 to -11.5), or -12.7 kg. A loss of 15% or more occurred in 50.5% on semaglutide and 4.9% on placebo [1]. In an open-label head-to-head trial, weight changed by -13.7% (95% CI -14.9 to -12.6) on semaglutide and -20.2% (95% CI -21.4 to -19.1) on tirzepatide at 72 weeks [2].
Population
1,961 adults with a BMI of 30 or more, or 27 or more with a weight-related condition, without diabetes [1]; 751 adults with obesity without type 2 diabetes [2].
Sources
[1], [2]
Caveats
Both trials added lifestyle intervention or diet and activity. STEP 1 was funded by Novo Nordisk [1]; the head-to-head trial by Eli Lilly, maker of tirzepatide [2].
Limited

Weight loss at the 7.2 mg dose

One trial found the 7.2 mg dose lowered weight about 19% at 72 weeks, 3 points more than 2.4 mg, in adults with obesity without diabetes.

The numbers and sources
Effect
At 72 weeks, body weight changed by -18.7% on semaglutide 7.2 mg, -15.6% on 2.4 mg and -3.9% on placebo. The difference was -3.1 percentage points against 2.4 mg (95% CI -4.7 to -1.6) and -14.8 points against placebo (95% CI -16.2 to -13.4). Against 2.4 mg, the odds of losing 20% or more were 1.8 times higher (95% CI 1.3 to 2.4) and of losing 25% or more 2.4 times higher (95% CI 1.6 to 3.5). The difference in waist circumference against placebo was -11.7 cm (95% CI -13.0 to -10.4) [3].
Population
1,407 adults with a BMI of 30 or more without diabetes, 73.7% women, mean weight 113.0 kg, randomized 5 to 1 to 1 to 7.2 mg (1,005), 2.4 mg (201) or placebo (201), with a lifestyle intervention, for 72 weeks [3].
Sources
[3]
Caveats
One trial, with 201 people in the 2.4 mg comparison arm. Funded by Novo Nordisk [3]. Gastrointestinal events and dysesthesia were more common at 7.2 mg than at 2.4 mg (see Risks).
Why limited
This rests on one trial, of 1,407 people. Strength counts independent studies that agree, so one trial is limited at any size.
Limited

Keeping weight off while staying on treatment

One trial found people who stayed on semaglutide lost a further 7.9%, while those switched to placebo regained 6.9%. Only people who tolerated the full dose took part.

The numbers and sources
Effect
After 20 weeks on semaglutide (mean loss 10.6%), people randomized to continue lost a further 7.9% by week 68, while those switched to placebo regained 6.9%, a difference of -14.8 points (95% CI -16.0 to -13.5). Waist circumference fell 9.7 cm more and systolic blood pressure 3.9 mm Hg more with continued treatment [4].
Population
803 adults with overweight or obesity without diabetes, 79% women, mean weight 107.2 kg, in a 48-week randomized withdrawal [4].
Sources
[4]
Caveats
One trial. Only people who reached the full dose in the run-in were randomized, so the results describe people who tolerated it.
Limited

Heart attack, stroke and cardiovascular death

One large trial found major cardiovascular events in 6.5% on semaglutide against 8.0% on placebo in adults with heart disease and overweight, without diabetes.

The numbers and sources
Effect
A major cardiovascular event occurred in 6.5% on semaglutide and 8.0% on placebo (HR 0.80, 95% CI 0.72 to 0.90) [5].
Population
17,604 adults aged 45 or older with existing cardiovascular disease and a BMI of 27 or more, without diabetes, followed a mean of 39.8 months [5].
Sources
[5]
Caveats
One trial, though large. It enrolled people with heart disease, so it does not describe people without it. Funded by Novo Nordisk [5].
Why limited
This rests on one trial, of 17,604 people. Strength counts independent studies that agree, so one trial is limited at any size.
Limited

Kidney disease in type 2 diabetes

One trial found a 24% lower risk of major kidney events, and fewer deaths, in adults with type 2 diabetes and chronic kidney disease.

The numbers and sources
Effect
Major kidney disease events (kidney failure, a fall in eGFR of 50% or more, or death from kidney or cardiovascular causes) occurred in 331 people on semaglutide and 410 on placebo (HR 0.76, 95% CI 0.66 to 0.88). The kidney-specific events alone gave HR 0.79 (95% CI 0.66 to 0.94). eGFR declined 1.16 mL/min/1.73 m2 a year more slowly, cardiovascular death was lower (HR 0.71, 95% CI 0.56 to 0.89) and death from any cause was lower (HR 0.80, 95% CI 0.67 to 0.95) [6].
Population
3,533 adults with type 2 diabetes and chronic kidney disease with raised urine albumin, 1.0 mg weekly, median follow-up 3.4 years [6].
Sources
[6]
Caveats
One trial, stopped early after a prespecified interim analysis. Funded by Novo Nordisk. It enrolled people with type 2 diabetes, so it does not describe kidney disease without diabetes [6].
Why limited
This rests on one trial, of 3,533 people. Strength counts independent studies that agree, so one trial is limited at any size.
LimitedVery common

Fatty liver inflammation and scarring (MASH)

One trial found liver inflammation resolved in 63% on semaglutide against 34% on placebo in adults with MASH. Outcomes were biopsy findings, not cirrhosis or liver failure.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
At 72 weeks, steatohepatitis resolved without worsening of fibrosis in 62.9% on semaglutide and 34.3% on placebo (difference 28.7 points, 95% CI 21.1 to 36.2). Fibrosis improved without worsening of steatohepatitis in 36.8% and 22.4% (difference 14.4 points, 95% CI 7.5 to 21.3). Both improved together in 32.7% and 16.1%. Body weight changed by -10.5% and -2.0% [7].
Population
The first 800 of 1,197 adults with biopsy-confirmed MASH and fibrosis stage 2 or 3, randomized 2 to 1 to 2.4 mg weekly or placebo (534 and 266) [7].
Sources
[7]
Caveats
An interim analysis of an ongoing 240-week trial. The outcomes are liver biopsy findings, not cirrhosis, liver failure or death. Funded by Novo Nordisk [7].
Why limited
This rests on one trial, of 1,197 people. Strength counts independent studies that agree, so one trial is limited at any size.

Doses studied

STEP 1, STEP 4, SELECT and ESSENCE used 2.4 mg by subcutaneous injection once weekly [1][4][5][7]. STEP UP used 7.2 mg once weekly, compared with 2.4 mg weekly and placebo [3]. FLOW used 1.0 mg weekly [6]. The head-to-head trial used the maximum tolerated dose of 1.7 mg or 2.4 mg weekly [2]. No trial of oral semaglutide was sourced for this page.

Risks

Reported risks8

ModerateVery common

Gastrointestinal effects and stopping treatment

Shown to raise nausea and diarrhea, mostly mild to moderate. Stopping for stomach effects was 4.5% against 0.8% on placebo in one trial.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Nausea and diarrhea were the most common adverse events, mostly mild to moderate. Discontinuation for gastrointestinal events was 4.5% on semaglutide and 0.8% on placebo [1]. In the withdrawal trial, gastrointestinal events occurred in 49.1% on continued semaglutide and 26.1% on placebo [4]. In SELECT, adverse events led to permanent discontinuation in 16.6% on semaglutide and 8.2% on placebo [5]. Gastrointestinal adverse events were more common on semaglutide in ESSENCE [7]. In FLOW, serious adverse events were reported in 49.6% on semaglutide and 53.8% on placebo [6]. In STEP UP, gastrointestinal adverse events occurred in 70.8% on 7.2 mg, 61.2% on 2.4 mg and 42.8% on placebo, and serious adverse events in 6.8%, 10.9% and 5.5% [3].
Population
Trial participants in [1], [3], [4], [5], [6] and [7].
Sources
[1], [3], [4], [5], [6], [7]
Caveats
STEP 1 describes the gastrointestinal events as typically transient and easing with time [1].
LimitedVery common

Altered skin sensation (dysesthesia) at 7.2 mg

One trial found altered skin sensation in 23% on 7.2 mg, 6% on 2.4 mg and under 1% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Dysesthesia was reported in 22.9% on semaglutide 7.2 mg, 6.0% on 2.4 mg and 0.5% on placebo [3].
Population
1,406 adults with obesity without diabetes who received at least one dose in STEP UP (1,004, 201 and 201) [3].
Sources
[3]
Caveats
One trial, funded by Novo Nordisk. The abstract does not report how long the sensations lasted or how severe they were [3].
Why limited
This rests on one trial, of 1,407 people. Strength counts independent studies that agree, so one trial is limited at any size.
ModerateCommon

Low blood pressure and fainting (label)

The label reports low blood pressure in 1.3% against 0.4% on placebo and fainting in 0.8% against 0.2%, more often with blood pressure medicines.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In the weight trials, reactions related to low blood pressure occurred in 1.3% on Wegovy and 0.4% on placebo, and fainting in 0.8% and 0.2%. Some were related to gastrointestinal reactions and fluid loss. Low blood pressure was more frequent in people also taking blood pressure medication. In adolescents it occurred in 2.3% against 0% [14].
Population
Adults and adolescents in the Wegovy weight trials, as reported in the label [14].
Sources
[14]
Caveats
Pooled figures from the manufacturer's trials, not broken out by trial.
ModerateHow often is not known

Gallbladder and bile duct disease

Shown to raise gallbladder and bile duct disease about 37% across GLP-1 drug trials, more at higher doses and longer use. The analysis pooled all GLP-1 drugs.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Across GLP-1 receptor agonist trials, the relative risk of gallbladder or biliary disease was 1.37 (95% CI 1.23 to 1.52), including gallstones (RR 1.27) and cholecystitis (RR 1.36). In weight loss trials it was 2.29 (95% CI 1.64 to 3.18). Risk was higher at higher doses and longer use [8].
Population
76 RCTs with 103,371 patients, mean age 57.8 [8].
Sources
[8]
Caveats
The meta-analysis pools all GLP-1 receptor agonists, not only semaglutide.
ModerateHow often is not known

Lean mass loss

Lean mass made up about 25% of weight lost in one review and 15% to 60% in others. A 2026 review called the muscle evidence too uncertain.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Sources measure the loss and describe it differently. A network meta-analysis found GLP-1 receptor agonists reduced lean mass by 0.86 kg (95% CI 0.42 to 1.30), about 25% of weight lost, while relative lean mass as a percentage of body weight was unchanged. Semaglutide 2.4 mg and tirzepatide 15 mg produced the most weight and fat loss and ranked among the least lean-sparing [9]. In a tirzepatide substudy, about 75% of weight lost was fat and 25% lean, the same split as placebo [10]. A review reports that in some trials lean mass made up 40 to 60% of total weight lost, and in others about 15% or less. It notes that lean mass includes organs, bone and water [11]. A 2026 meta-analysis found the muscle evidence too heterogeneous and imprecise for firm conclusions, with low to very low certainty [12].
Population
22 RCTs with 2,258 adults with diabetes or overweight [9]; 160 adults with DXA scans in SURMOUNT-1 [10]; trials summarized in a narrative review [11]; 19 studies, 2 comparative for muscle [12].
Sources
[9], [10], [11], [12]
Caveats
[11] is a narrative review, not a systematic one. Lean mass by DXA is not the same as muscle, and few trials measured strength or function [12].
LimitedHow often is not known

Optic nerve damage (NAION)

Linked to a higher rate of optic nerve damage in people with type 2 diabetes, about 1.4 more cases per 10,000 person-years than on SGLT-2 drugs.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In Danish and Norwegian registries, people with type 2 diabetes starting semaglutide had a higher rate of non-arteritic anterior ischemic optic neuropathy than those starting SGLT-2 inhibitors (HR 2.81, 95% CI 1.67 to 4.75), an absolute difference of 1.41 more cases per 10,000 person-years [13].
Population
61,377 semaglutide users with type 2 diabetes, 32 NAION events [13].
Sources
[13]
Caveats
An observational cohort with few events. The self-controlled analysis did not reach significance in either country [13].
LimitedHow often is not known

Acute kidney injury from dehydration (label warning)

The label reports acute kidney injury, some needing dialysis, mostly in people dehydrated from nausea, vomiting or diarrhea, and tells prescribers to monitor kidney function.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label reports postmarketing cases of acute kidney injury, some requiring hemodialysis, in people treated with semaglutide. Most occurred in people whose nausea, vomiting or diarrhea led to dehydration. The label tells prescribers to monitor kidney function in people reporting those reactions, especially when starting and raising the dose [14].
Population
Postmarketing reports summarized in the label [14].
Sources
[14]
Caveats
These are reports, not rates from a controlled comparison.
LimitedHow often is not known

Low blood sugar, and medicines taken by mouth (label)

The label warns of low blood sugar, reported more than on placebo in adults with type 2 diabetes. The tablet form raised levothyroxine levels 33%.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that Wegovy lowers blood glucose and can cause hypoglycemia, which was reported in more adults with type 2 diabetes on Wegovy than on placebo. For adolescents with type 2 diabetes, it says to consider lowering the dose of an insulin secretagogue such as a sulfonylurea, or of insulin, to reduce that risk. Semaglutide delays stomach emptying, and in a study with the semaglutide tablet, levothyroxine exposure rose 33% (90% CI 1.25 to 1.42) [14].
Population
Wegovy trial participants and drug interaction studies, as reported in the label [14].
Sources
[14]
Caveats
The levothyroxine figure is from the tablet form. In studies of the 1 mg weekly injection, semaglutide did not affect the absorption of medicines taken by mouth [14].

Claims tested and not found

  1. That the weight stays off after stopping. One year after stopping, people who had taken semaglutide regained 11.6 points of the 17.3% they had lost, leaving a net loss of 5.6% [15]. In the withdrawal trial, those switched to placebo regained 6.9% over 48 weeks [4].

Sources

  1. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2021. https://doi.org/10.1056/NEJMoa2032183
  2. Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. New England Journal of Medicine. 2025. https://doi.org/10.1056/NEJMoa2416394
  3. Wharton S, Freitas P, Hjelmesæth J, et al. Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. The Lancet Diabetes & Endocrinology. 2025. https://doi.org/10.1016/S2213-8587(25)00226-8
  4. Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021. https://doi.org/10.1001/jama.2021.3224
  5. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine. 2023. https://doi.org/10.1056/NEJMoa2307563
  6. Perkovic V, Tuttle KR, Rossing P, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. New England Journal of Medicine. 2024. https://doi.org/10.1056/NEJMoa2403347
  7. Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. New England Journal of Medicine. 2025. https://doi.org/10.1056/NEJMoa2413258
  8. He L, Wang J, Ping F, et al. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Internal Medicine. 2022. https://doi.org/10.1001/jamainternmed.2022.0338
  9. Karakasis P, Patoulias D, Fragakis N, et al. Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis. Metabolism. 2025. https://doi.org/10.1016/j.metabol.2024.156113
  10. Look M, Dunn JP, Kushner RF, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes, Obesity and Metabolism. 2025. https://doi.org/10.1111/dom.16275
  11. Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes, Obesity and Metabolism. 2024. https://doi.org/10.1111/dom.15728
  12. Lopes Menezes ML, Güntzel Chiappa ME, Kloss RF, et al. Body Composition Remodelling During GLP-1-Based Therapy: A Systematic Review and Meta-Analysis Using a Hierarchical Physiological Framework. Diabetes, Obesity and Metabolism. 2026. https://doi.org/10.1111/dom.71220
  13. Simonsen E, Lund LC, Ernst MT, et al. Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish-Norwegian cohort study. Diabetes, Obesity and Metabolism. 2025. https://doi.org/10.1111/dom.16316
  14. U.S. Food and Drug Administration. WEGOVY (semaglutide) injection and tablets, prescribing information. Revised 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b
  15. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, Obesity and Metabolism. 2022. https://doi.org/10.1111/dom.14725

Everything in the library