Peptide Protocol IQ
FDA-approvedHuman evidence

Semaglutide

Also referred to as Ozempic, Wegovy, Rybelsus, NN9535

A long-acting GLP-1 receptor agonist. Among the most extensively studied compounds in this catalogue, with large randomised trials and regulatory approval for specific indications.

Molecule class
GLP-1 receptor agonist (acylated 31-amino-acid analogue)
Category
Incretin
Last evidence review
2026-08-23
Compare this compoundCheck interactionsSolution calculator
2
Human studies
0
Animal / in vitro
2
Graded claims
4,500
Participants

Derived from qualifying human evidence

  • Most commonly studied duration: 68 weeks. Most frequently reported duration among 2 qualifying human studies with a stated duration.
  • Longest qualifying human study: 176 weeks. Longest duration among qualifying human studies with a stated duration.

These figures are computed from the study records shown below. Records without a verified source identifier are excluded from the calculation.

Mechanism

What is being studied

Agonises the GLP-1 receptor, augmenting glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and acting on hypothalamic appetite circuits. Fatty-acid acylation and albumin binding extend the half-life to roughly one week.

Evidence

Claims, graded individually

Each statement below carries its own evidence level, its own confidence rating, and its own account of what remains unestablished. A compound does not have a single grade.

Metabolic & Body-Composition Research

AStrongHigh confidenceHuman evidence

Once-weekly semaglutide 2.4 mg was associated with substantially greater body-weight reduction than placebo over 68 weeks in adults with overweight or obesity and without diabetes.

What is not established

Durability after discontinuation, and outcomes beyond the trial duration in unselected populations, remain less well characterised than the on-treatment effect.

Supporting sources (1)
Randomised controlled trialHuman Identifier verified

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Wilding JPH, Batterham RL, Calanna S, et al. · New England Journal of Medicine · 2021 · n = 1,961

Population
Adults with BMI ≥30, or ≥27 with at least one weight-related coexisting condition; without diabetes
Endpoint
Percentage change in body weight and weight reduction of ≥5%
Route
Subcutaneous
Quantity as reported
2.4 mg weekly (16-week escalation from 0.25 mg)
Frequency
Once weekly
Duration
68 weeks

Result. Mean change in body weight was −14.9% with semaglutide versus −2.4% with placebo at week 68.

Adverse events. Nausea and diarrhoea were the most common events, typically transient and dose-escalation related; more discontinuations for gastrointestinal events than placebo.

Limitations. Participants without diabetes only; all participants received lifestyle intervention; 68-week duration does not address longer-term maintenance or discontinuation effects.

PMID33567185DOI10.1056/NEJMoa2032183NCTNCT03548935

Last evidence review: 2026-08-23

Metabolic & Body-Composition Research

BModerateModerate confidenceHuman evidence

Whether weight reduction persists after discontinuation is a separate question from on-treatment efficacy.

What is not established

Post-withdrawal regain has been reported in this drug class. Assuming persistence is not supported.

Supporting sources (2)
Randomised controlled trialHuman Identifier verified

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Wilding JPH, Batterham RL, Calanna S, et al. · New England Journal of Medicine · 2021 · n = 1,961

Population
Adults with BMI ≥30, or ≥27 with at least one weight-related coexisting condition; without diabetes
Endpoint
Percentage change in body weight and weight reduction of ≥5%
Route
Subcutaneous
Quantity as reported
2.4 mg weekly (16-week escalation from 0.25 mg)
Frequency
Once weekly
Duration
68 weeks

Result. Mean change in body weight was −14.9% with semaglutide versus −2.4% with placebo at week 68.

Adverse events. Nausea and diarrhoea were the most common events, typically transient and dose-escalation related; more discontinuations for gastrointestinal events than placebo.

Limitations. Participants without diabetes only; all participants received lifestyle intervention; 68-week duration does not address longer-term maintenance or discontinuation effects.

PMID33567185DOI10.1056/NEJMoa2032183NCTNCT03548935
Randomised controlled trialHuman Identifier verified

Tirzepatide for Obesity Treatment and Diabetes Prevention

Jastreboff AM, le Roux CW, Stefanski A, et al. · New England Journal of Medicine · 2024 · n = 2,539

Population
Adults with obesity or overweight and prediabetes
Endpoint
Progression to type 2 diabetes and sustained weight change over 176 weeks
Route
Subcutaneous
Quantity as reported
Maximum tolerated dose 10 mg or 15 mg weekly
Frequency
Once weekly
Duration
176 weeks

Result. Reported substantially lower progression to type 2 diabetes versus placebo with sustained weight reduction over the treatment period; weight regain was observed after treatment withdrawal.

Adverse events. Consistent with the established gastrointestinal profile of the class.

Limitations. Prediabetes population only; the post-withdrawal regain finding is directly relevant to any assumption that effects persist after stopping.

PMID39536238DOI10.1056/NEJMoa2410819NCTNCT04184622

Last evidence review: 2026-08-23

Human evidence

2 human studies catalogued

Human and non-human evidence are kept strictly separate. They are never pooled, averaged, or presented as a single body of support.

Randomised controlled trialHuman Identifier verified

Once-Weekly Semaglutide in Adults with Overweight or Obesity

Wilding JPH, Batterham RL, Calanna S, et al. · New England Journal of Medicine · 2021 · n = 1,961

Population
Adults with BMI ≥30, or ≥27 with at least one weight-related coexisting condition; without diabetes
Endpoint
Percentage change in body weight and weight reduction of ≥5%
Route
Subcutaneous
Quantity as reported
2.4 mg weekly (16-week escalation from 0.25 mg)
Frequency
Once weekly
Duration
68 weeks

Result. Mean change in body weight was −14.9% with semaglutide versus −2.4% with placebo at week 68.

Adverse events. Nausea and diarrhoea were the most common events, typically transient and dose-escalation related; more discontinuations for gastrointestinal events than placebo.

Limitations. Participants without diabetes only; all participants received lifestyle intervention; 68-week duration does not address longer-term maintenance or discontinuation effects.

PMID33567185DOI10.1056/NEJMoa2032183NCTNCT03548935
Randomised controlled trialHuman Identifier verified

Tirzepatide for Obesity Treatment and Diabetes Prevention

Jastreboff AM, le Roux CW, Stefanski A, et al. · New England Journal of Medicine · 2024 · n = 2,539

Population
Adults with obesity or overweight and prediabetes
Endpoint
Progression to type 2 diabetes and sustained weight change over 176 weeks
Route
Subcutaneous
Quantity as reported
Maximum tolerated dose 10 mg or 15 mg weekly
Frequency
Once weekly
Duration
176 weeks

Result. Reported substantially lower progression to type 2 diabetes versus placebo with sustained weight reduction over the treatment period; weight regain was observed after treatment withdrawal.

Adverse events. Consistent with the established gastrointestinal profile of the class.

Limitations. Prediabetes population only; the post-withdrawal regain finding is directly relevant to any assumption that effects persist after stopping.

PMID39536238DOI10.1056/NEJMoa2410819NCTNCT04184622

Pharmacology

Reported parameters

Half-life

7.0 days

Approximately 7 days, supporting once-weekly administration in the trials.

Visualise this half-life →

Routes studied

  • Subcutaneous
  • Oral

Evidence from one route does not transfer to another. Topical, oral, and injected administration can produce entirely different exposure from the same quantity.

Regulatory status

FDA-approved products exist for type 2 diabetes and for chronic weight management, with specific labelled populations. Compounded semaglutide has been the subject of FDA communications and is not the same as an approved product.

Storage as documented

Refrigerated per approved product labelling; consult the labelling for the specific product.

Safety

Signals reported in the literature

This lists what has been reported. It is not a complete safety profile, and for several compounds in this catalogue no systematic safety surveillance exists at all.

  • Gastrointestinal events are the most common in trials (nausea, vomiting, diarrhoea, constipation)
  • Boxed warning regarding thyroid C-cell tumours in rodents; contraindicated in medullary thyroid carcinoma and MEN 2 per labelling
  • Pancreatitis reported; gallbladder events reported at increased frequency
  • Weight regain reported following discontinuation

Interactions

Register entries involving this compound

semaglutide ↔ tirzepatide

Redundant receptor agonism with additive gastrointestinal and gastric-emptying effects. No trial has studied these two agents together, and neither product's labelling contemplates concurrent use.

Limitations. No study has evaluated the combination. The concern is mechanistic redundancy, which is a reasoning-based conclusion rather than an observed interaction.

semaglutide ↔ insulin

Approved labelling for GLP-1 receptor agonists addresses concomitant insulin and the associated hypoglycaemia risk, including guidance on insulin adjustment.

Limitations. Magnitude depends on the insulin regimen and the individual.

semaglutide ↔ sulfonylureas

Hypoglycaemia risk with concomitant sulfonylurea is addressed in approved labelling.

Limitations. Risk is regimen-dependent.

semaglutide ↔ orally administered medications

Approved labelling notes the potential to affect absorption of concomitant oral medications. The clinical significance depends on the specific medication and its therapeutic index.

Limitations. Effect varies substantially by medication. Narrow-therapeutic-index medications warrant the most attention.

semaglutide ↔ anticholinergic and opioid medications

Both classes independently slow gastrointestinal transit. Combined effect on motility is a reasoning-based concern supported by the known pharmacology of each.

Limitations. No dedicated interaction studies. Mechanistic reasoning only.

nad-plus ↔ semaglutide

No interaction meeting our evidence criteria is currently documented between these compounds.

Limitations. Absence of evidence is not evidence of safety. This pair has not been the subject of a dedicated interaction study.

Open the full interaction explorer →

Limitations

What the evidence cannot tell you

Given as much prominence as the findings, because for most compounds in this category it is the more important half.

  • Trial populations were specific and generally excluded participants with diabetes in the obesity programmes
  • Long-term data beyond the trial durations remain limited for some endpoints
  • Compounded and grey-market products are not the studied product and may differ in identity, purity, and concentration

Reference

Evidence grading key

AStrong

Multiple high-quality human trials, or strong systematic-review or meta-analytic evidence.

BModerate

Human controlled evidence exists, but replication or sample size is limited.

CPreliminary

Small human studies, observational evidence, or early-phase clinical work.

DPreclinical

Predominantly animal or in-vitro evidence. No adequate human outcome data.

EMechanistic

Biological plausibility or mechanistic reasoning without adequate outcome evidence.

XInsufficient / conflicting

Evidence is absent, irreconcilable, or too weak to support any directional statement.

Related

Other compounds studied in the same research areas

Tirzepatide

A dual incretin receptor agonist with large randomised evidence including a 176-week readout that also reported post-withdrawal weight regain.

Retatrutide

An investigational triple agonist with a published phase 2 trial. It is not approved, and phase 3 outcome data are not established.

Cagrilintide

An investigational amylin analogue studied alone and in combination with semaglutide. Combination programme readouts continue to evolve.

Tesamorelin

A GHRH analogue with phase 3 randomised evidence in one specific population: adults with HIV-associated abdominal lipodystrophy.