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Semaglutide

GLP-1 receptor agonist

Also known as GLP-1 receptor agonist, Ozempic, Wegovy, Rybelsus

A long-acting GLP-1 receptor agonist with large phase III programmes in type 2 diabetes, obesity, and cardiovascular outcomes. One of the few entries here where the evidence base is genuinely deep.

Guide updated Sep 2, 2026Literature checked Sep 2, 20263 curated studies58 literature recordsBaseline editorial

Overview

In shortA copy of a natural gut hormone, redesigned to last a week instead of minutes. It is one of the most heavily tested peptides on this site, with tens of thousands of people across trials in diabetes, weight and heart outcomes. The argument here is about how much and how long, not about whether it does anything.

Semaglutide is an acylated analogue of human glucagon-like peptide-1, engineered for a long plasma half-life so it can be given weekly rather than daily. It is among the most extensively trialled peptides in modern medicine, with tens of thousands of participants across the SUSTAIN (type 2 diabetes), STEP (obesity), and SELECT (cardiovascular outcomes) programmes.

It is worth being explicit about why this entry looks different from most of the compendium: the questions here are about magnitude, durability, tolerability, and access. Not about whether the compound does anything. Very little else in this catalogue is at that stage.

Mechanism

In shortYour gut makes a hormone that tells your body to release insulin and tells your brain you are full, but it breaks down within minutes. This copies that hormone and survives far longer. It also slows how fast your stomach empties.

Semaglutide binds the GLP-1 receptor, a class B G-protein-coupled receptor, and reproduces several effects of endogenous GLP-1 while resisting the DPP-4 degradation that gives native GLP-1 a half-life of minutes.

The characterised effects are glucose-dependent insulin secretion from pancreatic beta cells, suppression of glucagon release, slowed gastric emptying, and reduced appetite. The appetite effect is the one most often described loosely: receptor expression in the human CNS is concentrated in the hypothalamus and brainstem rather than distributed across cortex, and a good deal of behavioural work attributing effects to broad central receptor engagement rests on rodent distribution data that does not transfer cleanly.

Evidence

In shortIn one large trial people lost about 15% of their body weight over 68 weeks, against about 2.4% on placebo. Another found fewer heart attacks and strokes in people who already had heart disease. Still argued: most of the weight returns after stopping, and how much of what is lost is muscle.

Strong and consistent for glycaemic control and weight, across large randomised trials with pre-registered endpoints.

The most-cited results: STEP 1 reported roughly 15% mean body weight reduction at 68 weeks against about 2.4% on placebo in adults with obesity. SELECT reported a reduction in major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity, without diabetes.

The open questions are about what happens after: weight regain following discontinuation is substantial in the extension data, and long-term outcomes beyond the trial windows are still accumulating. The composition of the weight lost, and how much of it is lean mass, remains actively argued.

Safety

In shortMostly stomach trouble, worst while the dose is being raised, and bad enough that some people stop. Rarer but documented: pancreas and gallbladder problems. Not for people with a personal or family history of one specific thyroid cancer. It is a prescription medicine and needs a doctor.

The common adverse effects are gastrointestinal, nausea, vomiting, diarrhoea, constipation, and are dose-related and usually most pronounced during escalation. Discontinuation for GI intolerance is meaningful in the trial data.

Documented concerns include pancreatitis, gallbladder disease, and a rodent-derived thyroid C-cell tumour signal that underpins a contraindication in people with a personal or family history of medullary thyroid carcinoma or MEN2. Cases of gastroparesis and of aspiration under anaesthesia have driven periprocedural guidance changes.

This is a prescription medicine that requires medical supervision. Discussion of compounded and grey-market supply is common and is exactly where this community's rules bite hardest.

Regulatory status

In shortApproved in many countries for type 2 diabetes, and at higher doses for weight management, with heart protection added more recently. What it is approved for, and what you can actually get, varies a lot by country.

Approved in many jurisdictions for type 2 diabetes and, at higher doses, for chronic weight management, with a cardiovascular indication added more recently. Formulations, approved indications, and reimbursement differ substantially by country.

Compounded versions occupy a legally contested space that has moved repeatedly and differs by jurisdiction. Nothing in this entry should be read as a statement about legality where you are.

The literature

3 studies indexed. Findings and limitations get equal weight, on purpose.

Always check the primary source

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Everything above is free to read. What an account opens is the evidence underneath it: 3 studies with their limitations, and the regimen each trial actually reported.

  • Every study, with what it found and what it cannot show
  • The limitations, given the same weight as the findings
  • The dose each named trial administered, where recorded
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The wider literature

17 indexed papers and 41 registered trials mentioning Semaglutide, straight from PubMed and ClinicalTrials.gov. 35 of 41 administer it; the rest measure it. These have not been read by us. Unlike the studies above, they carry no findings and no limitations written by anyone here, because writing either would mean claiming a reading nobody has done. They are a starting point for yours.

Registered trials (41)

  1. GLP-1 RA for Stage 1 Type 1 Diabetes

    Children's Hospital Medical Center, Cincinnati2027NCT07430332

    interventionalphase2not yet recruitingn=15

  2. Combatting Muscle Loss in Obese Adult Patients on GLP-1 Medications Through Dietary Counseling and Exercise During Treatment Evaluates Whether a 12-week Exercise and Individualized Nutrition Program Can Reduce Muscle and Bone Loss and Improve Strength, Fitness, and Function in Obese Adults on GLP-1

    William Marsh Rice University2026NCT07554417

    interventionalphase4not yet recruitingn=20

  3. Glycemic Velocity and Early Retinal Microvascular Change With GLP-1RA Versus SGLT2i Initiation in Type 2 Diabetes (GLIDE)

    Thammasart University Hospital2026NCT07723820

    observationalnot yet recruitingn=126

  4. GLP-1 RA on Liver OMICS in MASLD

    Medical College of Wisconsin2026NCT06982378

    observationalwithdrawnn=0

  5. A Two-armed Real-world Study of Ozempic (OW Semaglutide) to Evaluate Its Adherence and Persistence Compared With Other Anti-diabetic Drugs Among Adult T2DM Patients in China

    Novo Nordisk A/S2026NCT07456774

    observationalenrolling by invitationn=100000

  6. Can Fat-Burning Shots Boost Fertility? Comparing Weight-Loss Injections vs. Healthy Habits for Obese Men With Low Sperm Health

    First Affiliated Hospital of Wenzhou Medical University2026NCT07179120

    interventionalphase2not yet recruitingn=180

  7. Incretin Microdosing for Cardiometabolic Health in People With HIV

    The University of Texas Health Science Center, Houston2026NCT07325500

    interventionalphase2recruitingn=30

  8. Effect of Semaglutide on Embryo Quality in Overweight and Obese Patients Undergoing In Vitro Fertilization.

    Fundacion Dexeus2026NCT07242534

    interventionalphase4recruitingn=62

  9. Comparing Facial Aging Between Identical Twins With 3D Imaging

    Ponsky Facial Aesthetics And Plastic Surgery, Llc2026NCT07760532

    observationalnot yet recruitingn=200

  10. Real-world Canadian Retrospective Study Evaluating Longitudinal Semaglutide Use on Cardio-Kidney-Metabolic Outcomes

    LMC Diabetes & Endocrinology Ltd.2026NCT07424430

    observationalnot yet recruitingn=400

  11. Semaglutide Delivered Epi-Intradermally by Microarray Patch (VX-201) Versus Subcutaneous Administration in Healthy Overweight and Obese Participants

    Terrestrial Bio, Inc.2026NCT07673900

    interventionalphase1recruitingn=62

  12. A Phase III Clinical Study to Evaluate the Efficacy and Safety of GZR18 Injection in Adult Type 2 Diabetes Mellitus

    Gan & Lee Pharmaceuticals.2025NCT06778967

    interventionalphase3active not recruitingn=1100

  13. A Biomarker-targeted Clinical Trial to Optimize Treatment for Patients With Chronic Kidney Disease

    Peter Rossing2025NCT07239570

    interventionalphase4recruitingn=125

  14. Response to Semaglutide in Non-diabetic Obese Patients With Varying Degrees of Insulin Resistance

    ETH Zurich2025NCT06856291

    observationalrecruitingn=40

  15. Tolerance of a High Protein Nutrition Shake in Individuals on GLP-1

    Kate Farms Inc2025NCT07096739

    interventionalnacompletedn=20

  16. The Safety, Tolerability, and Pharmacokinetics of of SYH9017 in Chinese Participants With Overweight and Obesity

    CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.2025NCT06830343

    interventionalphase1recruitingn=66

  17. Study of Adult Patients Residing in Argentina Diagnosed With Type 2 Diabetes Treated With a New Formulation of Semaglutide, Both Oral and Subcutaneous, in a Real-world Setting at 3 Months, 6 Months, and 1 Year of Follow-up, Quantifying the Reduction in Glycated Hemoglobin

    Hospital Italiano de Buenos Aires2025NCT07621419

    observationalrecruitingn=145

  18. The Role of the Amylin Analogue Cagrilintide in Bone Metabolism

    Novo Nordisk A/S2025NCT07010432

    interventionalphase1recruitingn=144

  19. Glucagon-like Peptide 1 (GLP-1) Receptor Agonist Therapy and Exercise Training in People With Obesity

    Washington University School of Medicine2025NCT07091500

    interventionalnarecruitingn=40

  20. DUTCH Weight Control in Atrial Fibrillation Study

    Rijnstate Hospital2024NCT06184633

    interventionalphase4recruitingn=280

  21. Gastric Ultrasound To Assess Gastric Contents In Patients On Semaglutide Therapy

    Nils Vlaeminck2024NCT06292065

    interventionalnacompletedn=88

  22. Impact of Semaglutide on Tobacco Use and Related Health Behaviors

    University of Oklahoma2024NCT06986993

    interventionalphase4recruitingn=40

  23. Effectiveness and Safety of Semaglutide Combined With Dietary Fiber (Soloways) in Adults With Overweight or Obesity

    S.LAB (SOLOWAYS)2023NCT06215196

    interventionalnacompletedn=81

  24. A Research Study Comparing Blood Levels of Medicines NNC0194-0499 and Semaglutide Administered as a Combination Formulation Versus Two Separate Formulations

    Novo Nordisk A/S2023NCT05766709

    interventionalphase1completedn=53

  25. Semaglutide in Comorbid Schizophrenia Spectrum Disorder and Obesity

    Centre for Addiction and Mental Health2022NCT05333003

    interventionalnaactive not recruitingn=92

  26. A Research Study to Compare Two Semaglutide Medicines in People With Type 2 Diabetes

    Novo Nordisk A/S2022NCT05478252

    interventionalphase3completedn=388

  27. A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight

    Novo Nordisk A/S2022NCT05567796

    interventionalphase3active not recruitingn=3400

  28. SEMAGLUTIDE VERSUS GLP-1 RECEPTOR AGONISTS. EFFECTIVENESS , SAFETY AND QUALITY OF LIFE IN PATIENTS WITH DIABETES MELLITUS 2. OBSERVATIONAL, PROSPECTIVE AND MULTICENTER STUDY. SEVERAL STUDY.

    Jose Seijas Amigo2022NCT05136287

    observationalcompletedn=140

  29. Home-based Intervention With Semaglutide Treatment Of Neuroleptica-Related Prediabetes

    Jan Frystyk2022NCT05193578

    interventionalphase2completedn=154

  30. A Research Study Looking at How Oral Semaglutide Works in People With Type 2 Diabetes in Saudi Arabia, as Part of Local Clinical Practice

    Novo Nordisk A/S2022NCT05230589

    observationalcompletedn=194

  31. A Research Study of How Oral Semaglutide Tablets Work in Healthy People Who Are Chinese

    Novo Nordisk A/S2019NCT04016974

    interventionalphase1completedn=32

  32. A Research Study to Compare Two Forms of Semaglutide in Two Different Pen-injectors in People With Overweight or Obesity

    Novo Nordisk A/S2019NCT04012255

    interventionalphase1terminatedn=29

  33. Non-Alcoholic Fatty Liver Disease, the HEpatic Response to Oral Glucose, and the Effect of Semaglutide (NAFLD HEROES)

    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)2019NCT03884075

    interventionalphase2recruitingn=104

  34. Exercise and GLP-1 RA on Insulin Secretion

    University of Copenhagen2019NCT04383197

    interventionalnaunknownn=30

  35. Treating PCOS With Semaglutide vs Active Lifestyle Intervention

    University of Colorado, Denver2019NCT03919929

    interventionalphase2phase3completedn=60

  36. Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity

    Novo Nordisk A/S2018NCT03574597

    interventionalphase3completedn=17604

  37. Effects of Liraglutide in Chronic Obstructive Pulmonary Disease

    Claus Bogh Juhl2018NCT03466021

    interventionalphase4completedn=40

  38. A Research Study to Compare Semaglutide to Insulin Aspart, When Taken Together With Metformin and Insulin Glargine, in People With Type 2 Diabetes

    Novo Nordisk A/S2018NCT03689374

    interventionalphase3completedn=2274

  39. Dose-finding of Semaglutide Administered Subcutaneously Once Daily Versus Placebo and Liraglutide in Subjects With Type 2 Diabetes

    Novo Nordisk A/S2015NCT02461589

    interventionalphase2completedn=706

  40. Investigating the Influence of Oral Semaglutide on Pharmacokinetics of Metformin and Digoxin in Healthy Subjects

    Novo Nordisk A/S2014NCT02249910

    interventionalphase1completedn=32

  41. Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drug-naïve Subjects With Type 2 Diabetes

    Novo Nordisk A/S2014NCT02054897

    interventionalphase3completedn=388

Papers (17)

  1. Semaglutide therapy for metabolic dysfunction-associated steatohepatitis: November 2025 updates to AASLD Practice Guidance.

    Bansal MB, et al.Hepatology (Baltimore, Md.)2026PMID 41201884

    journal articlepractice guidelinereview

  2. The Ethics of Ozempic and Wegovy.

    Ryan N, et al.Journal of medical ethics2026PMID 39848681

    journal article

  3. Otolaryngologic Side Effects of GLP-1 Receptor Agonists.

    Khan FI, et al.The Laryngoscope2025PMID 39936458

    journal article

  4. Natural Weight Loss or "Ozempic Face": Demystifying A Social Media Phenomenon.

    Carboni A, et al.Journal of drugs in dermatology : JDD2024PMID 38206146

    journal article

  5. Use of glucagon-like peptide-1 receptor agonists in eating disorder populations.

    Bartel S, et al.The International journal of eating disorders2024PMID 38135891

    reviewjournal article

  6. Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.

    Karagiannis T, et al.Diabetologia2024PMID 38613667

    journal articlesystematic reviewnetwork meta-analysis

  7. GLP-1 agonists: A review for emergency clinicians.

    Long B, et al.The American journal of emergency medicine2024PMID 38241775

    journal articlereview

  8. Assessment of Thyroid Carcinogenic Risk and Safety Profile of GLP1-RA Semaglutide (Ozempic) Therapy for Diabetes Mellitus and Obesity: A Systematic Literature Review.

    Feier CVI, et al.International journal of molecular sciences2024PMID 38673931

    journal articlesystematic review

  9. Real-world persistence and adherence to glucagon-like peptide-1 receptor agonists among obese commercially insured adults without diabetes.

    Gleason PP, et al.Journal of managed care & specialty pharmacy2024PMID 38717042

    journal article

  10. Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Moiz A, et al.The American journal of cardiology2024PMID 38679221

    journal articlesystematic reviewmeta-analysisresearch support, non-u.s. gov't

  11. Implications of Ozempic and Other Semaglutide Medications for Facial Plastic Surgeons.

    Humphrey CD, et al.Facial plastic surgery : FPS2023PMID 37541662

    journal article

  12. As Ozempic's Popularity Soars, Here's What to Know About Semaglutide and Weight Loss.

    Suran MJAMA2023PMID 37099334

    journal article

  13. Wegovy (semaglutide): a new weight loss drug for chronic weight management.

    Singh G, et al.Journal of investigative medicine : the official publication of the American Federation for Clinical Research2022PMID 34706925

    journal articlereview

  14. GLP-1 receptor agonists: an updated review of head-to-head clinical studies.

    Trujillo JM, et al.Therapeutic advances in endocrinology and metabolism2021PMID 33767808

    journal articlereview

  15. Semaglutide (Ozempic) for weight loss.

    The Medical letter on drugs and therapeutics2021PMID 33830968

    journal article

  16. Semaglutide: First Global Approval.

    Dhillon SDrugs2018PMID 29363040

    journal articlereview

  17. Semaglutide.

    2006PMID 30000039

    review

Discussion

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For Research & Educational Discussion Only. Not Medical Advice

This guide is educational reference material compiled from published literature. It is not medical advice, not a recommendation, and not a substitute for a clinician who knows your history. Nothing here should be used to make a decision about your own health without one.

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