GLP-1 Status Tracker
Semaglutide Status: Trials, Approvals, and What Changed
A dated, wire-service tracker covering semaglutide's clinical trial pipeline, regulatory history by branded product, and the most recent data readouts.
Semaglutide is an FDA-approved GLP-1 receptor agonist available under the branded names Ozempic (subcutaneous, type 2 diabetes, approved 2017), Rybelsus (oral, type 2 diabetes, approved 2019), and Wegovy (subcutaneous, chronic weight management, approved 2021). Research-chemical versions of semaglutide sold outside those branded products are not FDA-approved. Active trials are now testing semaglutide in cardiovascular disease, chronic kidney disease, metabolic dysfunction-associated steatohepatitis, and Alzheimer's disease.
Compound Overview
Semaglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist developed by Novo Nordisk. It mimics the endogenous GLP-1 hormone, which is released from intestinal L-cells after eating and acts on receptors in the pancreas, brain, and gastrointestinal tract. The compound has a half-life of approximately one week in humans, which allows once-weekly subcutaneous dosing in its injectable forms.
The molecule was first described in peer-reviewed literature around 2012 and entered human trials shortly after. Its structural backbone is derived from human GLP-1 with a fatty-acid side chain attached to allow albumin binding, extending its circulation time compared with earlier GLP-1 agents like exenatide or liraglutide. That pharmacokinetic profile made it a priority compound for Novo Nordisk's late-stage development program.
Semaglutide belongs to the same GLP-1 receptor agonist class as liraglutide and dulaglutide, but its extended half-life and higher receptor affinity distinguish it pharmacologically. The compound is now one of the most-studied peptides in modern metabolic medicine, with more than 50 registered clinical trials on ClinicalTrials.gov as of mid-2025.
What Are the Current FDA Approval Milestones?
Three branded semaglutide products hold FDA approval, and each approval is specific to that product's formulation, indication, and manufacturer. Ozempic (semaglutide injection, 0.5 mg, 1 mg, and 2 mg) received FDA approval in December 2017 for glycemic control in adults with type 2 diabetes and to reduce major adverse cardiovascular events in adults with type 2 diabetes and established cardiovascular disease.
Rybelsus (semaglutide tablets, 7 mg and 14 mg) received FDA approval in September 2019, making it the first oral GLP-1 receptor agonist approved in the United States. Its indication covers glycemic control in adults with type 2 diabetes. The oral formulation uses an absorption enhancer called sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) to allow uptake through the gastric mucosa.
Wegovy (semaglutide injection, 2.4 mg) received FDA approval in June 2021 for chronic weight management in adults with obesity (BMI 30 or above) or overweight (BMI 27 or above) with at least one weight-related comorbidity. In March 2024, the FDA expanded Wegovy's label to include reduction of major adverse cardiovascular events in adults with obesity or overweight and established cardiovascular disease, based on the SELECT trial. Research-chemical semaglutide sold by compounding pharmacies or peptide vendors outside these three branded products carries none of these approvals.
Key Trial Readouts: Numbers and Dates
The SUSTAIN trial program, which ran from roughly 2015 through 2019, established semaglutide's glycemic and cardiovascular profile across eight large randomized controlled trials. SUSTAIN-6, published in the New England Journal of Medicine in November 2016, enrolled 3,297 participants with type 2 diabetes at high cardiovascular risk. Over 104 weeks, participants receiving semaglutide showed a 26% relative risk reduction in major adverse cardiovascular events compared with placebo.
The STEP trial program evaluated Wegovy's 2.4 mg dose for weight management. STEP 1, published in the New England Journal of Medicine in March 2021, enrolled 1,961 adults with obesity or overweight without diabetes. Participants receiving semaglutide 2.4 mg lost a mean of 14.9% of body weight over 68 weeks versus 2.4% for placebo. STEP 2 enrolled 1,210 adults with type 2 diabetes and reported mean weight loss of 9.6% with semaglutide 2.4 mg versus 3.4% with placebo over 68 weeks.
The SELECT trial, results published in the New England Journal of Medicine in November 2023, enrolled 17,604 adults with pre-existing cardiovascular disease and obesity or overweight but without diabetes. Over a median follow-up of 34.2 months, Wegovy reduced the rate of major adverse cardiovascular events by 20% versus placebo. That readout directly supported the March 2024 label expansion. The FLOW trial, results published in the New England Journal of Medicine in May 2024, enrolled 3,533 adults with type 2 diabetes and chronic kidney disease. Ozempic reduced the composite kidney and cardiovascular outcome by 24% versus placebo, prompting an FDA label update for Ozempic in late 2024 to include slowing of kidney disease progression.
What Is Currently in the Active Trial Pipeline?
As of mid-2025, several large Phase 3 trials are ongoing or recently completed with results pending. The EVOKE and EVOKE Plus trials (NCT04777396 and NCT04777409) are evaluating oral semaglutide in adults with early Alzheimer's disease. Combined enrollment exceeds 3,700 participants. These are the first large randomized trials testing a GLP-1 receptor agonist specifically for cognitive outcomes in Alzheimer's disease, and results are expected in 2025.
The ESSENCE trial program is evaluating semaglutide 2.4 mg in metabolic dysfunction-associated steatohepatitis (MASH), a liver condition previously called nonalcoholic steatohepatitis. Phase 3 data from ESSENCE, published in the New England Journal of Medicine in May 2024, showed that 62.9% of participants receiving semaglutide achieved histological resolution of MASH without worsening of fibrosis at 72 weeks, compared with 34.3% for placebo, in a cohort of 800 participants. Novo Nordisk submitted a supplemental new drug application to the FDA based on these data.
Additional active trials are examining semaglutide in heart failure with preserved ejection fraction (STEP-HFpEF program), obstructive sleep apnea, polycystic ovary syndrome, and non-alcoholic fatty liver disease in adolescents. The pediatric obesity indication for Wegovy received FDA approval in December 2022 for adolescents aged 12 and older, based on the STEP TEENS trial, which enrolled 201 participants aged 12 to 17.
What Changed This Quarter?
The most significant regulatory change in late 2024 was the FDA's update to Ozempic's prescribing information to reflect the FLOW trial kidney outcomes data. The label now includes language about reducing the risk of sustained decline in kidney function, kidney failure, and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. This was a label expansion for an already-approved product, not a new approval.
On the compounding and supply side, the FDA removed semaglutide from its drug shortage list in October 2024, which has direct implications for compounding pharmacies that had been permitted to produce copies of Ozempic and Wegovy under shortage exemptions. The agency subsequently issued guidance indicating that compounded semaglutide products are not FDA-approved and that the shortage exemption no longer applies. Enforcement actions and legal challenges from compounding pharmacies were ongoing as of mid-2025.
Novo Nordisk's oral semaglutide program is also advancing. A higher-dose oral formulation (25 mg and 50 mg tablets, studied under the OASIS and PIONEER PLUS trial programs) is under FDA review for weight management as of early 2025. PIONEER PLUS, published in The Lancet in July 2023, enrolled 667 adults with obesity and reported mean weight loss of 15.1% with 50 mg oral semaglutide over 68 weeks. If approved, this would be the first oral GLP-1 agent approved specifically for weight management in the United States.
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Frequently asked questions
Is the semaglutide sold by peptide vendors the same as Ozempic or Wegovy?
No. Ozempic and Wegovy are FDA-approved branded drugs manufactured by Novo Nordisk under strict pharmaceutical controls. Research-chemical semaglutide sold by peptide vendors or compounding pharmacies outside the branded products is not FDA-approved, has not undergone the same manufacturing oversight, and carries none of the approved indications. The FDA removed semaglutide from its drug shortage list in October 2024, which eliminated the shortage-based exemption that had previously allowed some compounding.
What did the SELECT trial find, and why does it matter for Wegovy's label?
The SELECT trial, published in the New England Journal of Medicine in November 2023, enrolled 17,604 adults with obesity or overweight and pre-existing cardiovascular disease but without diabetes. Over a median of 34.2 months, Wegovy (semaglutide 2.4 mg) reduced major adverse cardiovascular events by 20% versus placebo. The FDA used these data to expand Wegovy's label in March 2024 to include cardiovascular risk reduction, making it the first weight-management drug in the U.S. with an approved cardiovascular outcomes indication.
What is the current status of semaglutide in Alzheimer's disease research?
Two large Phase 3 trials, EVOKE and EVOKE Plus (ClinicalTrials.gov identifiers NCT04777396 and NCT04777409), are evaluating oral semaglutide in adults with early Alzheimer's disease. Combined enrollment exceeds 3,700 participants. These trials are randomized controlled trials in humans, which places them at a higher evidence tier than the preclinical and observational data that preceded them. Results are expected in 2025. No semaglutide product is currently approved for any neurological indication.
Sources
- Marso et al., 2016, New England Journal of Medicine (SUSTAIN-6) SUSTAIN-6 cardiovascular outcomes RCT data
- Wilding et al., 2021, New England Journal of Medicine (STEP 1) STEP 1 weight loss RCT primary results
- Lincoff et al., 2023, New England Journal of Medicine (SELECT) SELECT cardiovascular outcomes trial in obesity
- Perkovic et al., 2024, New England Journal of Medicine (FLOW) FLOW kidney outcomes RCT supporting label update
- ClinicalTrials.gov, EVOKE trial NCT04777396 Phase 3 semaglutide Alzheimer's disease trial
Related reading
Medical disclaimer: This status report is educational and informational only and is not medical advice, diagnosis, or treatment. Retatrutide and the GLP-class research compounds discussed here may not be approved by the FDA for human use outside prescribed clinical contexts, and vendor-sourced material has not been evaluated by the FDA for safety, efficacy, or quality. Always consult a licensed physician or pharmacist before making any health-related decision.