# Semaglutide

- Canonical: https://residue.info/c/semaglutide/
- Also called: NN9535, Ozempic, Wegovy, Rybelsus
- Evidence grade: A (Approved / regulatory-grade). FDA-approved as injection and tablet for type 2 diabetes, weight management and cardiovascular risk reduction; supported by large outcomes trials.
- Status: FDA-approved — Ozempic (2017), Rybelsus (2019), Wegovy (2021)
- PubChem CID: 56843331
- Updated: 2026-10-19 · Reviewed by: Residue Editorial Team

Semaglutide is a GLP-1 receptor agonist, injected weekly or taken daily by mouth. It is FDA-approved as Ozempic and Rybelsus (type 2 diabetes) and Wegovy (weight management, cardiovascular risk) [1][2]. In STEP 1, weight fell 14.9% versus 2.4% on placebo over 68 weeks [3]; in SELECT, major cardiovascular events fell 20% [4]. Half-life: about 7 days [5].

## Key findings
- STEP 1 (1,961 adults without diabetes, 2.4 mg weekly): weight change −14.9% versus −2.4% with placebo at 68 weeks; 50.5% lost 15% or more [3]. (anchor: https://residue.info/c/semaglutide/#kf-pmid-33567185)
- SELECT (17,604 adults with cardiovascular disease and overweight or obesity, no diabetes): major adverse cardiovascular events 6.5% versus 8.0% (hazard ratio 0.80) over a mean 39.8 months [4]. (anchor: https://residue.info/c/semaglutide/#kf-pmid-37952131)
- STEP 5 showed the effect persisting to two years: −15.2% versus −2.6% at 104 weeks [6]. (anchor: https://residue.info/c/semaglutide/#kf-pmid-36216945)
- One year after stopping, STEP 1 extension participants had regained about two-thirds of the weight they had lost [7]. (anchor: https://residue.info/c/semaglutide/#kf-pmid-35441470)
- Discontinuation for adverse events was 16.6% with semaglutide versus 8.2% with placebo in SELECT [4]. (anchor: https://residue.info/c/semaglutide/#kf-pmid-37952131-2)

## Effects by system
- Body weight (grade A): Approved for long-term weight reduction in adults and adolescents 12+ with obesity [2]; −14.9% at 68 weeks in STEP 1 [3]. (anchor: https://residue.info/c/semaglutide/#effect-body-weight)
- Glycemic control (grade A): Approved as an adjunct to diet and exercise in type 2 diabetes, as injection and tablet [1][8]. (anchor: https://residue.info/c/semaglutide/#effect-glycemic-control)
- Cardiovascular (grade A): Wegovy is indicated to reduce major adverse cardiovascular events in adults with established cardiovascular disease and obesity or overweight [2], based on SELECT [4]. (anchor: https://residue.info/c/semaglutide/#effect-cardiovascular)
- Kidney (grade A): Ozempic is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death in type 2 diabetes with chronic kidney disease [1]. (anchor: https://residue.info/c/semaglutide/#effect-kidney)
- Weight maintenance (grade B): Continuing after a 20-week run-in: −7.9% versus +6.9% on switching to placebo [9]. (anchor: https://residue.info/c/semaglutide/#effect-weight-maintenance)
- Gastrointestinal (adverse) (grade A): Nausea and diarrhea most common, typically transient [3]; GI events 82.2% versus 53.9% over two years in STEP 5 [6]. (anchor: https://residue.info/c/semaglutide/#effect-gastrointestinal-adverse)

## How does Semaglutide work?

Semaglutide is an analog of human glucagon-like peptide-1 (GLP-1) that carries a fatty-acid side chain [10]. Labels for both the injection and tablet describe it as a GLP-1 receptor agonist [1][8]. A radiolabel study in healthy volunteers found intact semaglutide made up 69–83% of drug-related material in plasma; it is metabolized by proteolytic cleavage and beta-oxidation of the side chain, and urine is the main excretion route [10].

## How long does Semaglutide last in the body?

At 0.5 or 1 mg weekly, semaglutide's half-life is about seven days, so steady state takes four to five weeks. Like other GLP-1 receptor agonists it delays gastric emptying, which may affect absorption of oral medicines [5]. A 2024 systematic review found exposure rises with dose for both routes; oral exposure is sensitive to food, water volume and dosing conditions, and no dose adjustment was needed for renal or hepatic impairment [11].

## What did the clinical trials find?

**Weight management (STEP).** STEP 1 randomized adults with obesity, or overweight with a comorbidity, without diabetes to 2.4 mg weekly or placebo. At 68 weeks, weight had fallen 14.9% versus 2.4% (−15.3 kg versus −2.6 kg); 86.4% lost at least 5% and 50.5% at least 15% [3]. STEP 5 extended the comparison to 104 weeks: −15.2% versus −2.6% [6].

**Maintenance and withdrawal.** STEP 4 enrolled 803 people who had lost a mean 10.6% during a 20-week run-in. Those continuing lost a further 7.9% by week 68; those switched to placebo gained 6.9% [9]. The STEP 1 extension followed 327 participants for a year after stopping: they regained 11.6 of the 17.3 percentage points lost, and most cardiometabolic improvements reverted towards baseline [7].

**Cardiovascular outcomes (SELECT).** SELECT enrolled 17,604 adults aged 45 or older with established cardiovascular disease and a BMI of 27 or more, without diabetes. Over a mean 39.8 months, the primary composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke occurred in 6.5% on semaglutide and 8.0% on placebo (hazard ratio 0.80; 95% CI 0.72–0.90) [4]. This result underpins Wegovy's cardiovascular indication [2].

## What adverse events were reported in trials?

Gastrointestinal effects dominate. In STEP 1, nausea and diarrhea were the most common and were usually transient; 4.5% discontinued for gastrointestinal events versus 0.8% on placebo [3]. Over two years in STEP 5, gastrointestinal events were reported by 82.2% versus 53.9% [6]. In the much larger and longer SELECT trial, 16.6% stopped the drug for an adverse event versus 8.2% with placebo [4].

Six semaglutide applications appear in Drugs@FDA at our fetch: the Ozempic injection [12], Rybelsus tablets [13], a tablet application covering Rybelsus and Ozempic tablets [14], Wegovy injection [15], a Wegovy tablet approved in December 2025 [16], and a generic application whose marketing status is listed as "None (Tentative Approval)" [17].

The shortage that allowed widespread compounding is over. FDA's April 2026 statement notes semaglutide is not on the 503B bulks list or the drug-shortage list, and gives examples — such as semaglutide combined with vitamin B12 — that it may treat as essentially copies of approved products [18].

## What is still unknown?

- **Long-term maintenance.** Weight and cardiometabolic gains reverse after stopping [7]; durable strategies remain under study.
- **New indications.** Hundreds of registered studies test semaglutide in other conditions [19]; registration alone is not evidence.

## Frequently asked questions
**What is the difference between Ozempic, Wegovy and Rybelsus?**
All contain semaglutide. Ozempic (injection) and Rybelsus (tablet) are labeled for type 2 diabetes and related cardiovascular and kidney indications [1][8]. Wegovy is labeled for cardiovascular risk reduction in people with established cardiovascular disease and obesity or overweight, and for long-term weight reduction [2].

**What are the side effects of semaglutide?**
Gastrointestinal effects are the most common: in STEP 1, nausea and diarrhea were typically transient and mild to moderate, and 4.5% stopped because of gastrointestinal events versus 0.8% on placebo [3]. In SELECT, 16.6% discontinued for any adverse event versus 8.2% on placebo [4]. The FDA label lists all warnings [2].

**What is the half-life of semaglutide?**
About 7 days at 0.5 or 1 mg, so steady state is reached in 4–5 weeks [5]. Intact semaglutide accounts for 69–83% of circulating drug-related material [10].

**Do people regain weight after stopping semaglutide?**
In the STEP 1 extension, participants regained about two-thirds of their prior weight loss within a year of stopping [7]. In STEP 4, switching to placebo after 20 weeks led to a 6.9% gain [9].

**Does semaglutide reduce heart attacks and strokes?**
In SELECT, in people with cardiovascular disease and overweight or obesity but no diabetes, the composite of cardiovascular death, non-fatal heart attack or non-fatal stroke occurred in 6.5% versus 8.0% on placebo (hazard ratio 0.80) [4].

**Is compounded semaglutide still available?**
FDA declared the semaglutide shortage resolved in February 2025. Its April 2026 statement says semaglutide is not on the 503B bulks list or the shortage list, and restates the limits on 503A pharmacies compounding essentially-copies of approved products [18].

**What is semaglutide?**
Semaglutide is a GLP-1 receptor agonist given weekly by injection or daily by mouth. It is FDA-approved as Ozempic and Rybelsus for type 2 diabetes and as Wegovy for weight management and cardiovascular risk reduction [1][2].


## Sources
[1] OZEMPIC prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-07-30. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42bdd912-2393-44c4-b7e0-47672ca28991
[2] WEGOVY prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2024-04-23. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f5e548d0-cc79-4c34-a3f5-e20a5b8b6564
[3] Once-Weekly Semaglutide in Adults with Overweight or Obesity. Wilding JPH et al. N Engl J Med. 2021. https://pubmed.ncbi.nlm.nih.gov/33567185/
[4] Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. Lincoff AM et al. N Engl J Med. 2023. https://pubmed.ncbi.nlm.nih.gov/37952131/
[5] Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist. Hall S et al. Clin Pharmacokinet. 2018. https://pubmed.ncbi.nlm.nih.gov/29915923/
[6] Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Garvey WT et al. Nat Med. 2022. https://pubmed.ncbi.nlm.nih.gov/36216945/
[7] Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Wilding JPH et al. Diabetes Obes Metab. 2022. https://pubmed.ncbi.nlm.nih.gov/35441470/
[8] OZEMPIC, RYBELSUS prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-01-30. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=27f15fac-7d98-4114-a2ec-92494a91da98
[9] Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. Rubino D et al. JAMA. 2021. https://pubmed.ncbi.nlm.nih.gov/33755728/
[10] Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Jensen L et al. Eur J Pharm Sci. 2017. https://pubmed.ncbi.nlm.nih.gov/28323117/
[11] Clinical Pharmacokinetics of Semaglutide: A Systematic Review. Yang XD & Yang YY Drug Des Devel Ther. 2024. https://pubmed.ncbi.nlm.nih.gov/38952487/
[12] Drugs@FDA: OZEMPIC (NDA209637). NOVO; original approval 2017-12-05; Prescription, Discontinued. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=209637
[13] Drugs@FDA: RYBELSUS (NDA213182). NOVO NORDISK INC; original approval 2020-01-16; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213182
[14] Drugs@FDA: OZEMPIC, RYBELSUS (NDA213051). NOVO; original approval 2019-09-20; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213051
[15] Drugs@FDA: WEGOVY, WEGOVY HD, WEGOVY FLEXTOUCH (NDA215256). NOVO; original approval 2021-06-04; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=215256
[16] Drugs@FDA: WEGOVY (NDA218316). NOVO; original approval 2025-12-22; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=218316
[17] Drugs@FDA: SEMAGLUTIDE (ANDA220314). APOTEX INC; original approval 2026-04-07; None (Tentative Approval). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=220314
[18] FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. U.S. FDA, content current as of 04/01/2026. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize
[19] ClinicalTrials.gov registry search: semaglutide. 785 registered studies at fetch. https://clinicaltrials.gov/search?intr=semaglutide

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