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Semaglutide

GLP-1 receptor agonist

Status

Approved

Approved by the FDA and EMA as weekly injections and daily tablets for type 2 diabetes and weight management, with added US indications for cardiovascular and kidney risk reduction and (accelerated) MASH with fibrosis; the FDA declared the US shortage resolved on February 21, 2025, ending enforcement discretion for compounded copies on April 22, 2025 (503A pharmacies) and May 22, 2025 (503B outsourcing facilities).

Evidence

Strong

Several large placebo-controlled phase 3 programs (SUSTAIN, STEP, OASIS) and outcome trials (SUSTAIN-6, SELECT, FLOW, ESSENCE) support its approved uses.

Semaglutide is a long-acting, fatty-acid-modified analog of the gut hormone GLP-1. It is approved as weekly injections and daily tablets for type 2 diabetes and weight management, and to lower cardiovascular, kidney and liver-disease risks in specific groups.

Structure

31 residues
  1. aK20C18 fatty diacid via γGlu-2xOEG linker (albumin binding)

Point at a bead, or focus the chain and use the arrow keys, to name it. Pick a chemistry to highlight it.

Sequence as text
H-H-Aib-E-G-T-F-T-S-D-V-S-S-Y-L-E-G-Q-A-A-K-E-F-I-A-W-L-V-R-G-R-G-OH

What it is used for

  • Type 2 diabetes, glycemic control (approved)
  • Chronic weight management in adults and adolescents 12 and older (approved)
  • Reducing major cardiovascular events in type 2 diabetes or in obesity with cardiovascular disease (approved)
  • Slowing kidney disease progression in type 2 diabetes with chronic kidney disease (approved)
  • MASH with moderate to advanced liver fibrosis, US accelerated approval (approved)

How it works

Semaglutide activates the GLP-1 receptor. In the pancreas this increases glucose-dependent insulin release and lowers glucagon; in the brain it reduces appetite and food intake; it also slows stomach emptying. Two changes make it last about a week: an Aib residue at position 2 blocks breakdown by the enzyme DPP-4, and a C18 fatty diacid attached to Lys20 binds reversibly to albumin in the blood, slowing clearance.

How strong the evidence is

StrongSeveral large randomised controlled trials in people.

STEP 1 (1,961 adults without diabetes) found 14.9% mean weight loss at 68 weeks versus 2.4% with placebo. SELECT (17,604 adults with cardiovascular disease and overweight or obesity) cut major cardiovascular events by 20% (6.5% vs 8.0%). In type 2 diabetes, SUSTAIN-6 lowered cardiovascular events and FLOW reduced serious kidney outcomes by 24%. In ESSENCE, steatohepatitis resolved in 62.9% versus 34.3% with placebo. OASIS 4 found 13.6% weight loss at 64 weeks with the 25 mg daily tablet versus 2.2% with placebo, and STEP UP supported the 7.2 mg weekly dose.

Risks and side effects

  • Nausea, vomiting, diarrhea and constipation, mostly during dose escalation
  • Boxed warning: thyroid C-cell tumors in rodents; contraindicated with a personal or family history of medullary thyroid cancer or MEN 2
  • Acute pancreatitis, gallbladder disease and acute kidney injury from dehydration
  • Hypoglycemia when combined with insulin or sulfonylureas, and diabetic retinopathy complications in type 2 diabetes
  • Increased heart rate and risk of pulmonary aspiration during general anesthesia or deep sedation

Label dosing

Label (Wegovy injection): start at 0.25 mg once weekly and escalate every 4 weeks to a usual 2.4 mg weekly maintenance dose, which may be raised to a maximum of 7.2 mg if more weight loss is needed; Ozempic and the tablets follow separate schedules.

Summarised from the official prescribing information. Not a recommendation: dosing is decided with a prescriber.

Regulatory status

RegionYearApproved for
USFDA2017Type 2 diabetes (glycemic control); cardiovascular risk reduction added in 2020 and kidney disease risk reduction in 2025
USFDA2019Type 2 diabetes as a daily tablet; cardiovascular risk reduction added in 2025, with a reformulated tablet sold as Ozempic tablets from 2026
USFDA2021Chronic weight management (adults, and adolescents 12 and older from 2022); 25 mg daily tablet approved December 2025 and 7.2 mg weekly dose (Wegovy HD) March 2026
USFDA2024Reducing major cardiovascular events in adults with established cardiovascular disease and obesity or overweight
USFDA2025Noncirrhotic MASH with moderate to advanced liver fibrosis (accelerated approval)
EUEMA2018Type 2 diabetes
EUEMA2020Type 2 diabetes (oral tablet)
EUEMA2022Weight management in adults and adolescents 12 and older; oral tablet form approved in 2026

Status by country

JurisdictionStatusSource
USUnited StatesAuthorised medicineSource 2
EUEuropean UnionAuthorised medicineSource 13
UKUnited KingdomAuthorised medicineSource 17
AUAustraliaAuthorised medicineSource 18
CACanadaAuthorised medicineSource 19
Whether a medicine containing it is authorised, checked in each regulator’s records on Oct 1, 2026.

Status of every peptide by country

Trials of Semaglutide to watch

  1. Phase 3Active, not recruiting

    STEP Young(opens the source in a new tab)

    A Research Study on How Well Semaglutide Helps Children and Teenagers With Excess Body Weight Lose Weight

    Primary completion Oct 15, 2025210 participantsSponsor: Novo Nordisk A/SNCT05726227

  2. Phase 3Active, not recruiting

    TRANSCEND-T2D-2(opens the source in a new tab)

    Effect of Retatrutide Compared With Semaglutide in Adult Participants With Type 2 Diabetes and Inadequate Glycemic Control With Metformin With or Without SGLT2 Inhibitor (TRANSCEND-T2D-2)

    Primary completion Aug 27, 20261,250 participantsSponsor: Eli Lilly and CompanyNCT06260722

  3. Phase 3Active, not recruiting

    GLORY-3(opens the source in a new tab)

    A Study Comparing IBI362 vs Semaglutide in Chinese Overweight or Obese Adults With Metabolic Dysfunction-associated Fatty Liver Disease （MAFLD）

    Primary completion expected Dec 31, 2026479 participantsSponsor: Innovent Biologics (Suzhou) Co. Ltd.NCT06884293

  4. Phase 3Active, not recruiting

    REDEFINE 3(opens the source in a new tab)

    REDEFINE 3: A Research Study to See the Effects of CagriSema in People Living With Diseases in the Heart and Blood Vessels

    Primary completion expected Sep 1, 20277,101 participantsSponsor: Novo Nordisk A/SNCT05669755

  5. Phase 3Active, not recruiting

    FOCUS(opens the source in a new tab)

    A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes

    Primary completion expected Nov 7, 20271,500 participantsSponsor: Novo Nordisk A/SNCT03811561

  6. Phase 3Recruiting

    AMAZE 7(opens the source in a new tab)

    A Research Study Investigating How Well the Medicine Zenagamtide Helps People With Excess Body Weight Lose Weight Compared to Semaglutide

    Primary completion expected Oct 10, 2028650 participantsSponsor: Novo Nordisk A/SNCT07668414

  7. Phase 3Not yet recruiting

    AMAZE 8(opens the source in a new tab)

    AMAZE 8: A Research Study Investigating How Well the Medicine NNC0487-0111 Compared to Semaglutide Helps People With Excess Body Weight and Type 2 Diabetes Lose Weight

    Primary completion expected Dec 12, 20281,000 participantsSponsor: Novo Nordisk A/SNCT07400107

  8. Phase 3Completed

    CagriSema vs tirzepatide in obesity(opens the source in a new tab)

    A Research Study to See How Well CagriSema Compared to Tirzepatide Helps People With Obesity Lose Weight

    Primary completion Dec 8, 2025809 participantsSponsor: Novo Nordisk A/SNCT06131437

  9. Phase 3Completed

    REIMAGINE 2(opens the source in a new tab)

    A Research Study to See How Well CagriSema Compared to Semaglutide, Cagrilintide and Placebo Lowers Blood Sugar and Body Weight in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor

    Primary completion Nov 19, 20252,734 participantsSponsor: Novo Nordisk A/SNCT06065540

  10. Phase 3Completed

    DREAMS-3(opens the source in a new tab)

    A Study Comparing IBI362 vs Semaglutide in Chinese Adults With Early Type 2 Diabetes and Obesity

    Primary completion Sep 17, 2025349 participantsSponsor: Innovent Biologics (Suzhou) Co. Ltd.NCT06184568

  11. Phase 3Completed

    EVOKE(opens the source in a new tab)

    A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease (EVOKE)

    Primary completion Sep 16, 20251,840 participantsSponsor: Novo Nordisk A/SNCT04777396

  12. Phase 3Completed

    EVOKE Plus(opens the source in a new tab)

    A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease (EVOKE Plus)

    Primary completion Sep 15, 20251,840 participantsSponsor: Novo Nordisk A/SNCT04777409

  13. Phase 2Completed

    SEMALCO(opens the source in a new tab)

    Does Semaglutide Reduce Alcohol Intake in Patients With Alcohol Use Disorder and Comorbid Obesity?

    Primary completion Jul 31, 2025108 participantsSponsor: Psychiatric Centre RigshospitaletNCT05895643

All trials to watch

Timeline

  1. 2028

    1. AMAZE 8
    2. AMAZE 7

  2. 2027

    1. FOCUS
    2. REDEFINE 3

  3. 2026

    1. GLORY-3
    2. ResearchREMODEL: primary kidney MRI outcomes show no significant difference versus placebo
    3. ResearchSTEP UP exploratory analysis finds reduced liver fat with semaglutide
    4. RegulatoryFDA says compounded GLP-1s with added vitamins are still copies of approved drugs
    5. SafetyTGA finds undeclared semaglutide in counterfeit retatrutide after hospitalization
    6. RegulatoryWADA keeps GLP-1 drugs off its 2027 Prohibited List and continues monitoring
    7. ResearchESC heart failure guidelines back semaglutide or tirzepatide in HFpEF with obesity
    8. RegulatoryAppeals court upholds FDA decisions ending the tirzepatide and semaglutide shortages
Show 46 earlier events

  1. 2026

    1. TRANSCEND-T2D-2
    2. RegulatoryFDA warning letters reject 'research use only' labels on online GLP-1 peptide sales
    3. ResearchBMJ review of 262 trials: semaglutide the only obesity drug linked to lower mortality
    4. MarketMedicare GLP-1 Bridge starts, covering obesity drugs for a $50 monthly copay
    5. MarketHealth Canada approves first generic semaglutide for weight loss
    6. ResearchAmerican College of Physicians names semaglutide and tirzepatide first-line obesity drugs
    7. ApprovalEMA committee recommends oral Wegovy tablets for weight management in the EU
    8. RegulatoryFDA proposes barring outsourcing facilities from compounding semaglutide and tirzepatide
    9. ResearchSemaglutide cuts heavy drinking days in trial of alcohol use disorder with obesity
    10. MarketGeneric semaglutide launches in India on the day the core patent expires
    11. ApprovalFDA approves Wegovy HD, a 7.2 mg semaglutide dose, under priority voucher program
    12. Trial resultCagriSema misses non-inferiority goal against tirzepatide in REDEFINE 4
    13. RegulatoryFDA vows crackdown on compounded GLP-1s after Hims markets a semaglutide pill
    14. SafetyUK regulator strengthens GLP-1 warnings on severe, necrotising and fatal pancreatitis
    15. SafetyFDA asks makers to drop suicidal-thoughts warning from GLP-1 weight-loss drug labels

  2. 2025

    1. ApprovalFDA approves Wegovy pill, the first oral GLP-1 drug for weight loss
    2. CagriSema vs tirzepatide in obesity
    3. RegulatoryWHO issues first guideline on GLP-1 medicines for obesity, with conditional backing
    4. Trial resultSemaglutide fails to slow Alzheimer's disease in phase 3 evoke and evoke+ trials
    5. REIMAGINE 2
    6. STEP Young
    7. DREAMS-3
    8. EVOKE
    9. EVOKE Plus
    10. RegulatoryWHO adds semaglutide, tirzepatide and other GLP-1 drugs to its essential medicines list
    11. ApprovalFDA grants accelerated approval to Wegovy for MASH with moderate to advanced fibrosis
    12. SEMALCO
    13. SafetyEMA lists NAION optic nerve damage as a very rare side effect of semaglutide
    14. SafetyFDA warns of counterfeit Ozempic 1 mg pens found in the US drug supply chain
    15. MarketNovo Nordisk launches NovoCare Pharmacy selling Wegovy at $499 a month to cash payers
    16. RegulatoryFDA declares semaglutide shortage resolved, ending mass compounding of copies
    17. ApprovalFDA approves Ozempic to slow kidney disease in adults with type 2 diabetes
    18. ResearchVeterans study maps GLP-1 drug benefits and risks across 175 health outcomes
    19. Approved, US (FDA)Noncirrhotic MASH with moderate to advanced liver fibrosis (accelerated approval)

  3. 2024

    1. Trial resultCagriSema delivers 22.7% weight loss in REDEFINE 1, below Novo's 25% expectation
    2. Trial resultSURMOUNT-5: tirzepatide beats semaglutide on weight loss in head-to-head trial
    3. SafetyFDA warns of overdoses from dosing errors with compounded semaglutide vials
    4. SafetyEMA safety committee finds no causal link between GLP-1 drugs and suicidal thoughts
    5. ApprovalFDA approves Wegovy to cut heart attack and stroke risk in adults with obesity
    6. Approved, US (FDA)Reducing major cardiovascular events in adults with established cardiovascular disease and obesity or overweight

  4. 2022

    1. Approved, EU (EMA)Weight management in adults and adolescents 12 and older; oral tablet form approved in 2026

  5. 2021

    1. Approved, US (FDA)Chronic weight management (adults, and adolescents 12 and older from 2022); 25 mg daily tablet approved December 2025 and 7.2 mg weekly dose (Wegovy HD) March 2026

  6. 2020

    1. Approved, EU (EMA)Type 2 diabetes (oral tablet)

  7. 2019

    1. Approved, US (FDA)Type 2 diabetes as a daily tablet; cardiovascular risk reduction added in 2025, with a reformulated tablet sold as Ozempic tablets from 2026

  8. 2018

    1. Approved, EU (EMA)Type 2 diabetes

  9. 2017

    1. Approved, US (FDA)Type 2 diabetes (glycemic control); cardiovascular risk reduction added in 2020 and kidney disease risk reduction in 2025

Articles about Semaglutide

Sources

  1. 01Wegovy (semaglutide) injection and tablets: prescribing information(opens the source in a new tab) DailyMed, U.S. National Library of Medicine, 2026
  2. 02Ozempic (semaglutide) injection: prescribing information(opens the source in a new tab) DailyMed, U.S. National Library of Medicine, 2026
  3. 03Rybelsus and Ozempic (semaglutide) tablets: prescribing information(opens the source in a new tab) DailyMed, U.S. National Library of Medicine, 2026
  4. 04Semaglutide (D10025): sequence and structure entry(opens the source in a new tab) KEGG DRUG
  5. 05Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1)(opens the source in a new tab) New England Journal of Medicine, 2021
  6. 06Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)(opens the source in a new tab) New England Journal of Medicine, 2023
  7. 07Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6)(opens the source in a new tab) New England Journal of Medicine, 2016
  8. 08Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW)(opens the source in a new tab) New England Journal of Medicine, 2024
  9. 09Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis (ESSENCE)(opens the source in a new tab) New England Journal of Medicine, 2025
  10. 10Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity (OASIS 4)(opens the source in a new tab) New England Journal of Medicine, 2025
  11. 11Wegovy pill FDA approval (company announcement)(opens the source in a new tab) Novo Nordisk, 2025
  12. 12FDA approves Novo Nordisk's new Wegovy HD injection(opens the source in a new tab) Novo Nordisk via PR Newswire, 2026
  13. 13Ozempic: EPAR (European public assessment report)(opens the source in a new tab) European Medicines Agency, 2026
  14. 14Wegovy: EPAR (European public assessment report)(opens the source in a new tab) European Medicines Agency, 2026
  15. 15Novo Nordisk financial report for the first six months of 2026 (Form 6-K)(opens the source in a new tab) U.S. Securities and Exchange Commission (EDGAR), 2026
  16. 16FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize(opens the source in a new tab) U.S. Food and Drug Administration, 2025
  17. 17Ozempic 1 mg solution for injection in pre-filled pen: Summary of Product Characteristics(opens the source in a new tab) electronic medicines compendium (emc), 2026
  18. 18OZEMPIC 0.25/0.5 mg semaglutide 1.34 mg/mL solution for injection pre-filled pen (308324)(opens the source in a new tab) Therapeutic Goods Administration
  19. 19Drug Product Database: Ozempic (DIN 02471469)(opens the source in a new tab) Health Canada, 2026
  1. In clinical trialsAmycretinUnimolecular GLP-1 and amylin receptor agonistNo single sequence68 WADA banned
  2. Not approvedAOD-9604Modified growth hormone fragment (research peptide)16 WADA banned
  3. In clinical trialsCagrilintideLong-acting amylin analog (amylin and calcitonin receptor agonist)37 WADA banned
  4. ApprovedDulaglutideGLP-1 receptor agonist (Fc fusion protein)31
  5. ApprovedExenatideGLP-1 receptor agonist39

Educational information, not medical advice. Talk to a licensed clinician before starting, stopping or changing any medicine.