RYBELSUS (semaglutide)
RYBELSUS (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated for adults with type 2 diabetes mellitus. It is used as an adjunct to diet and exercise to improve glycemic control and to reduce the risk of major adverse cardiovascular events, such as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. The medication is specifically intended for patients with type 2 diabetes who are at high risk for these cardiovascular events.
How RYBELSUS Works
Semaglutide functions as a GLP-1 receptor agonist that binds to and activates the GLP-1 receptor, a target for the physiological hormone GLP-1. This activation reduces blood glucose by stimulating insulin secretion and lowering glucagon secretion in a glucose-dependent manner. Additionally, the drug causes a minor delay in gastric emptying in the early postprandial phase. Its long half-life is maintained through albumin binding, which protects the drug from metabolic degradation and renal clearance.
Details
- Status
- Prescription
- First Approved
- 2019-09-20
- PDUFA Date
- 2026-10-18 (145d)
- Patent Cliff
- 2039
- Revenue
- $770M (Q4-2025)
- Routes
- ORAL
- Dosage Forms
- TABLET
RYBELSUS Approval History
What RYBELSUS Treats
2 indicationsRYBELSUS is approved for 2 conditions since its original approval in 2019. These indications span multiple therapeutic areas including oncology, immunology, and more.
- Improvement of glycemic control in adults with type 2 diabetes mellitus
- Reduction in the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus at high risk for these events
RYBELSUS Boxed Warning
RISK OF THYROID C-CELL TUMORS • In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS and OZEMPIC tablets cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions ( 5.1 ), Nonclinical Toxicology ( 13.1 )] . • RYBELSUS and OZEMPIC tablet...
WARNING: RISK OF THYROID C-CELL TUMORS • In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS and OZEMPIC tablets cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions ( 5.1 ), Nonclinical Toxicology ( 13.1 )] . • RYBELSUS and OZEMPIC tablets are contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Contraindications ( 4 )] . Counsel patients regarding the potential risk for MTC with the use of RYBELSUS or OZEMPIC tablets and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with RYBELSUS or OZEMPIC tablets [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )]. WARNING: RISK OF THYROID C-CELL TUMORS See full prescribing information for complete boxed warning. • In rodents, semaglutide causes thyroid C-cell tumors. It is unknown whether RYBELSUS and OZEMPIC tablets cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined ( 5.1 , 13.1 ). • RYBELSUS and OZEMPIC tablets are contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors ( 4 , 5.1 ).
RYBELSUS Target & Pathway
ProTarget
A hormone released after eating that stimulates insulin secretion, suppresses glucagon, slows gastric emptying, and promotes satiety. GLP-1 receptor agonists mimic these effects, improving blood sugar control and promoting weight loss in diabetes and obesity.
RYBELSUS Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
Direct competitors
Same target(s) AND same indication — head-to-head.
MoA expansion candidates
Same target(s), different indications — where else is this mechanism being explored?
Indication competitors
Same indication, different mechanism — what else might this patient receive?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
What's emerging in RYBELSUS's indications
See all emerging drugs →Phase 3 candidates targeting molecules with no FDA-approved drug, in indications RYBELSUS treats. First-in-class if their pivotal trials read out positive.
Clinical Trial Registry
252 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT03884075 | 190072 19-DK-0072 | Ph 2 | recruiting | Non-Alcoholic Fatty Liver Disease, the HEpatic Response to Oral Glucose, and the Effect of Semaglutide (NAFLD HEROES) |
| NCT06745284 | 1404-0045 U1111-1309-3679 | Ph 1 | active not recruiting | A Study to Test Whether Survodutide Improves How the Body Uses Energy and Breaks Down Fat in People With Obesity |
| NCT06015893 | 10001603 001603-DA | Ph 2 | recruiting | Semaglutide Therapy for Alcohol Reduction (STAR) |
| NCT06884293 | CIBI362B303 | Ph 3 | active not recruiting | A Study Comparing IBI362 vs Semaglutide in Chinese Overweight or Obese Adults With Metabolic Dysfunction-associated Fatty Liver Disease （MAFLD） |
| NCT07059377 GLP1-SC | HM74061 | Ph 3 | recruiting | Semaglutide for Smoking Cessation in Patients With Diabetes |
| NCT05514535 results posted | NN9535-4801 U1111-1267-0312, 2021-004392-13 | Ph 3 | completed | A Research Study to Look Into How Semaglutide, Together With a Lower Dose of Insulin Glargine, Compares to a Higher Dose of Insulin Glargine Alone in People With Type 2 Diabetes (SUSTAIN OPTIMIZE) |
| NCT05586802 KLIN-HEALTH | PZ00P3_202151 | Ph 3 | recruiting | Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome |
| NCT06299098 COURAGE | R1033-OB-2288 | Ph 2 | active not recruiting | A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss, Fat Loss, and Lean Mass Preservation |
| NCT07547878 RAPID-CKD | 026-271 | Ph 4 | not yet recruiting | Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD) |
| NCT07527195 RASMUS | NN9838-8411 U1111-1321-8655, 2025-522920-28 | Ph 1 | recruiting | Understanding the Effect of CagriSema, Cagrilintide, and Semaglutide on Muscle Health (Role of Amylin Signature in Muscle Health) |
| NCT07415954 | NN9662-8160 U1111-1324-0310, 2025-523260-20 | Ph 2 | recruiting | A Research Study Comparing How Well Different Doses of the Medicine NNC0662-0419 Lower Blood Sugar in People With Type 2 Diabetes |
| NCT06388187 | NN9838-7749 U1111-1298-3451, 2023-509273-24 | Ph 3 | completed | A Research Study to See How Well Different Doses of CagriSema Help People With Excess Body Weight Lose Weight |
| NCT05567796 REDEFINE 1 | NN9838-4608 Universal Trial Number (UTN), 2020-005435-75 | Ph 3 | active not recruiting | A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight |
| NCT06534411 REIMAGINE 5 | NN9388-7741 U1111-1300-2590, 2023-509600-15 | Ph 3 | active not recruiting | A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Tirzepatide in People With Type 2 Diabetes Treated With Metformin, SGLT2 Inhibitor or Both |
| NCT07564414 | NN9838-7910 U1111-1323-0372, 2025-522488-14 | Ph 3 | not yet recruiting | A Research Study to Look at How Two Different Doses of CagriSema and One Dose of Semaglutide Help People Living With Obesity With or Without Type 2 Diabetes Lose Weight |
| NCT07282769 | IRB25-1571 | Ph 2 | not yet recruiting | Semaglutide (Wegovy) Treatment for Trichotillomania |
| NCT06975111 | 25-0943 U1111-1322-1036 | Ph 2, Ph 3 | recruiting | Focusing on the Menopausal Transition to Improve Mid-Life Women's Health |
| NCT03811561 FOCUS | NN9535-4352 U1111-1201-6256, 2017-003619-20 | Ph 3 | active not recruiting | A Research Study to Look at How Semaglutide Compared to Placebo Affects Diabetic Eye Disease in People With Type 2 Diabetes |
| NCT07284979 | K9531-3107 2025-523511-11-00 | Ph 3 | recruiting | Efficacy and Safety of KAI-9531 Administered Once Weekly Compared With Semaglutide and Placebo in Participants Living With Obesity Who Do Not Have Diabetes |
| NCT07487103 | QLG1091-301 | Ph 3 | not yet recruiting | Efficacy and Safety of QLG1091 vs Rybelsus as add-on to Metformin in Subjects With Type 2 Diabetes |
| NCT07554417 | IRB-FY2026-226 | Ph 4 | not yet recruiting | 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 |
| NCT05649137 results posted | NN9536-7545 2022-002235-60, U1111-1279-0359 | Ph 3 | completed | A Research Study to See How Semaglutide Helps People With Excess Weight and Type 2 Diabetes Lose Weight |
| NCT05646706 STEP UP results posted | NN9536-4999 U1111-1274-4259, 2022-000790-94 | Ph 3 | completed | A Research Study to See How Semaglutide Helps People With Excess Weight, Lose Weight (STEP UP) |
| NCT05726227 STEP Young | NN9536-4512 U1111-1266-3808, 2022-502922-41 | Ph 3 | active not recruiting | A Research Study on How Well Semaglutide Helps Children and Teenagers With Excess Body Weight Lose Weight |
| NCT06221969 | NN9388-4894 U1111-1282-5561, 2023-503789-21-00 | Ph 3 | completed | A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Tirzepatide in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor |
| NCT07511543 LEAST | LEAST | Ph 2 | not yet recruiting | Glucagon-like Peptide-1 Receptor Agonists for Endovascular Stroke Thrombectomy |
| NCT04822181 ESSENCE | NN9931-4553 U1111-1244-3678, 2019-004594-44 | Ph 3 | active not recruiting | Research Study on Whether Semaglutide Works in People With Non-alcoholic Steatohepatitis (NASH) |
| NCT07218354 CRAVE | 2041 | Ph 3 | not yet recruiting | Cessation or Reduction of Alcohol Consumption in Veterans: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of a GLP-1 Receptor Agonist Semaglutide in U.S. Veterans With Alcohol Use Disorder |
| NCT05202353 | 1404-0047 2021-000363-76, 2024-515417-17-00 | Ph 1 | recruiting | A Study in People With Obesity to Test the Effects of BI 456906 Compared With Semaglutide on Glucagon Receptor Activity in the Liver |
| NCT07523633 HASHTAG | The HASHTAG Study U1111-1327-8749, 2025-524163-21 | Ph 2 | recruiting | Effect of Semaglutide on Cannabis Use in Adults With Cannabis Use Disorder |
| NCT06260722 | 18805 J1I-MC-GZBZ | Ph 3 | active not recruiting | 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) |
| NCT07466017 | CS060380-MASH-CN-II-03 2024LP01824, CS060380-MASH-CN-II-03 | Ph 2 | recruiting | A Study of CS060380 Tablets in Patients With MASH and Obesity |
| NCT05813912 | NN1436-4910 2022-002847-24, U1111-1281-4752 | Ph 3 | completed | A Research Study to See How a New Weekly Insulin, Insulin Icodec When Given Along With Semaglutide Helps in Reducing the Blood Sugar Level in Patients With Type 2 Diabetes |
| NCT05144984 results posted | NN9389-4606 U1111-1259-2741, 2020-004863-14 | Ph 2 | completed | A Research Study Looking at How Well a Combination of the Medicines Semaglutide and NNC0480-0389 Works in People With Type 2 Diabetes |
| NCT07112872 | BP45703 2024-520322-11-00 | Ph 2 | active not recruiting | A Study to Compare Different Doses of RO7795081 With a Placebo or Semaglutide in People With Type 2 Diabetes |
| NCT06604624 | HD1916-003 | Ph 3 | completed | Semaglutide in Treatment of Obesity |
| NCT07087795 | NN6497-8316 U1111-1315-5122, 2024-519533-38 | Ph 1 | active not recruiting | A Study to See the Effect of NNC0194-0499 Alone or in Combination With Semaglutide on Blood Sugar Control in People Living With Type 1 Diabetes |
| NCT06323174 REIMAGINE 1 | NN9388-4895 2022-502677-42, U1111-1283-0404 | Ph 3 | completed | A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in People With Type 2 Diabetes Treated With Diet and Exercise |
| NCT07253285 | NN9838-4968 U1111-1299-4751, 2023-509176-42 | Ph 3 | recruiting | A Research Study on How Well Cagrilintide and CagriSema Work in Children and Adolescents With Excess Body Weight |
| NCT07272343 | 2022efyA04 | Ph 4 | recruiting | The Impact of Semaglutide Compared to Energy Restriction on Type 2 Diabetes |
| NCT06803888 | 24-915 | Ph 4 | active not recruiting | Bariatric Surgery vs. Semaglutide vs. Tirzepatide |
| NCT06131372 | NN9388-7700 U1111-1291-5907, 2023-505857-42 | Ph 2 | completed | A Research Study to See if Kidney Damage in People With Chronic Kidney Disease and Type 2 Diabetes Living With Overweight or Obesity Can be Reduced by CagriSema Compared to Semaglutide, Cagrilintide and Placebo |
| NCT07505303 | EC0011 | Ph 2 | not yet recruiting | MIST (Metabolic Intervention With Semaglutide and THR-β Therapy) Trial |
| NCT04777409 EVOKE Plus | NN6535-4725 U1111-1259-2920, 2023-506918-45 | Ph 3 | completed | A Research Study Investigating Semaglutide in People With Early Alzheimer's Disease (EVOKE Plus) |
| NCT07040592 HARP | 2000033919_c 1P01AA029545-01 | Ph 2 | recruiting | Off-Label Medications for Alcohol Use Disorder Among Patients With HIV: Pilot Study 3 Semaglutide |
| NCT06222437 | 046.OBG.2023.D | Ph 1 | withdrawn | Semaglutide and Polycystic Ovarian Syndrome: an Emerging Treatment Strategy |
| NCT07485062 MOTIVATE | 128008 528313 | Ph 4 | not yet recruiting | Exercise and Diabetes Interventions to Improve Brain Health in Older Adults With Type 2 Diabetes |
| NCT07227948 | HSC-MS-25-0412 R01DA062720-01 | Ph 2 | recruiting | Repurposing Semaglutide for the Treatment of Cocaine Use Disorder |
| NCT07483801 DECODE | DECODE (A097165) | Ph 4 | not yet recruiting | DECODE - Haemodynamic Effects Of Semaglutide and Tirzepatide - a Series of Pilot Studies |
| NCT05119179 | HSC-MS-21-0297 5R01DK127084 | Ph 4 | recruiting | Pharmacogenetics of the Response to GLP-1 in Mexican-Americans With Prediabetes |
Showing 50 of 252 trials
Active Pipeline
Ongoing clinical trials by development phase
Key Completed Trials
Completed studies with published results, ranked by significance
Trial Timeline
Full development history with FDA approval milestones
Understanding FDA Approval Types
| Count | Type | What it means |
|---|---|---|
| - | ORIG | Original approval - drug first enters market |
| - | SUPPL - Efficacy | New indication (new disease/condition approved) |
| - | SUPPL - Labeling | Label text changes (warnings, dosing updates) |
| - | SUPPL - Manufacturing | Production changes (new facility) |
| - | SUPPL - Chemistry | Formulation changes (new dosage strength) |
Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.
RYBELSUS FDA Label Details
Indications & Usage
FDA Label (PDF)RYBELSUS is indicated for the treatment of Improvement of glycemic control in adults with type 2 diabetes mellitus; Reduction in the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus at high risk for these events.
WARNING: RISK OF THYROID C-CELL TUMORS • In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether RYBELSUS and OZEMPIC tablets cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC),...
RYBELSUS Patents & Exclusivity
Patents (16 active)
Exclusivity
Pro Intelligence Preview
Deep insights for RYBELSUS
Revenue Insights
- • Q4-2025: $770M
- • Historical trend analysis
Patent Timeline
- • Cliff: 2039
- • 201 active patents
Trial Analysis
- • Clinical trial tracking
- • Development stage analysis
Competitive Landscape
- • Competitor tracking
- • Same target/indication analysis
Full approval history • All patents • Revenue trends • Competitor analysis
Data Sources
Data sourced from official FDA and NIH databases. Click links to verify on original sources.