Peptide Checkup

Compound record · Metabolic (incretin-based)

Semaglutide

Also Wegovy · Ozempic · Rybelsus · Sema

GLP-1 receptor agonist

Metabolic (incretin-based)Evidence · StrongApproved medicine (for specific indications)

Once-weekly incretin medicine with the largest weight-management evidence base

Check my fitCompare

Record reviewed 1 September 2026 · 6 references

In the AERVYN range

2 pens carry Semaglutide

Class
GLP-1 receptor agonist
Route
Weekly subcutaneous injection (oral form for diabetes)
Trial participants
> 25,000 across STEP and SELECT programmes
Licensed weight loss
≈ 15% mean at 68 weeks (STEP 1)
Prescription
Required in UK, US, EU, AU, CA

01 Overview

What Semaglutide is

Summary

Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist authorised for type 2 diabetes and, at 2.4 mg weekly, for chronic weight management in adults with obesity or overweight with a weight-related condition. It has been studied in tens of thousands of trial participants and has cardiovascular-outcome data.

Mechanism

Mimics the gut hormone GLP-1: enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying and acts on appetite centres in the brain to reduce hunger and food intake.

Routes studiedSubcutaneous injection, Oral
Anti-dopingNot prohibited

02 Evidence by goal

What has been shown, for which goal

Grades follow one scale across the site. Strong overall means: multiple large randomised controlled trials or regulatory approval for this use.

  1. Weight management

    Strong

    In STEP 1 (n = 1,961), 2.4 mg weekly produced a mean 14.9% body-weight reduction at 68 weeks versus 2.4% with placebo, alongside diet and activity support.

  2. Fat loss / body composition

    Moderate

    DXA sub-studies show most weight lost is fat mass, but a meaningful proportion (roughly 25–40%) is lean mass; resistance training and protein intake are usually advised.

  3. Longevity

    Moderate

    SELECT (n = 17,604) showed a 20% relative reduction in major adverse cardiovascular events in adults with established cardiovascular disease and overweight/obesity, without diabetes.

  4. General wellbeing

    Limited

    Improvements in physical functioning scores were reported in weight-management trials; no direct evidence for energy or fatigue as a primary outcome.

03 Regulatory status

Where it is authorised, and for what

Status is recorded per jurisdiction from regulator sources and reviewed by hand. It is never inferred from another region's decision.

United Kingdom

Authorised

Authorised (MHRA) for type 2 diabetes and weight management; prescription-only.

Wegovy is licensed for weight management in adults with BMI ≥ 30, or ≥ 27 with a weight-related comorbidity, alongside diet and physical activity. NICE TA875 recommends it within specialist weight-management services for a maximum of two years. Prescription-only medicine.

StatusAuthorised
Status last reviewed1 September 2026
SourceOur maintained database — never inferred

04 Dosing research

What the evidence says about exposure

Published human studies and the doses, routes and durations they used — reported as research information, not a recommendation.

Research information — not a recommendation. These are the exposures used in published human studies, reported so you can see what has been tested. They are not dosing instructions and do not apply to any individual.

Study 01

STEP 1 — once-weekly semaglutide in adults with overweight or obesity

Wilding JPH et al., N Engl J Med 2021;384:989–1002 · Source

Phase 32021
Design
Randomised, double-blind, placebo-controlled
Population
Adults without diabetes with BMI ≥ 30, or ≥ 27 with ≥ 1 weight-related comorbidity
Participants
n = 1,961
Duration
68 weeks
Route
Subcutaneous injection
Doses studied
Escalated over 16 weeks: 0.25 mg → 0.5 mg → 1.0 mg → 1.7 mg → 2.4 mg once weekly (maintenance 2.4 mg)
Outcome at this exposure
Mean body-weight change −14.9% vs −2.4% with placebo; 86.4% lost ≥ 5% vs 31.5%.
Adverse events observed
Gastrointestinal events (nausea, diarrhoea, vomiting, constipation) in 74.2% vs 47.9%; treatment discontinuation for adverse events 7.0% vs 3.1%; gallbladder-related disorders 2.6% vs 1.2%.

Study 02

STEP 5 — two-year semaglutide 2.4 mg

Garvey WT et al., Nat Med 2022;28:2083–2091

Phase 32022
Design
Randomised, double-blind, placebo-controlled
Population
Adults with overweight or obesity without diabetes
Participants
n = 304
Duration
104 weeks
Route
Subcutaneous injection
Doses studied
2.4 mg once weekly after 16-week escalation
Outcome at this exposure
Mean weight change −15.2% vs −2.6% with placebo at week 104; effect maintained through two years.
Adverse events observed
Gastrointestinal events most common (82.2% vs 53.9%), mostly mild-to-moderate and transient.

Study 03

SELECT — cardiovascular outcomes in obesity without diabetes

Lincoff AM et al., N Engl J Med 2023;389:2221–2232

Phase 32023
Design
Randomised, double-blind, placebo-controlled, event-driven
Population
Adults ≥ 45 with established cardiovascular disease and BMI ≥ 27, without diabetes
Participants
n = 17,604
Duration
Mean 39.8 months
Route
Subcutaneous injection
Doses studied
2.4 mg once weekly
Outcome at this exposure
Major adverse cardiovascular events reduced by 20% (HR 0.80, 95% CI 0.72–0.90).
Adverse events observed
Serious adverse events lower with semaglutide (33.4% vs 36.4%); discontinuation for adverse events higher (16.6% vs 8.2%), mainly gastrointestinal.

05 Safety

Adverse effects and contraindications

Common effects seen in trials or reports, serious effects that warrant urgent review, and conditions under which use is not appropriate or needs assessment.

Common adverse effects

  • Nausea
  • Diarrhoea
  • Vomiting
  • Constipation
  • Abdominal pain and bloating
  • Headache
  • Fatigue
  • Injection-site reactions
  • Reduced appetite and early satiety

Serious adverse effects

  • Acute pancreatitis
  • Gallbladder disease (gallstones, cholecystitis)
  • Acute kidney injury from dehydration
  • Hypoglycaemia when combined with insulin or sulfonylureas
  • Worsening of diabetic retinopathy
  • Increased heart rate
  • Severe allergic reactions (rare)
  • Aspiration during anaesthesia due to retained stomach contents (label warning)

Contraindications

  • Personal or family history of medullary thyroid cancer or MEN2Do not use

    Contraindicated with a personal or family history of medullary thyroid carcinoma or MEN2 (boxed warning based on rodent thyroid C-cell tumours).

  • Previous pancreatitisDo not use

    Not recommended in people with a history of pancreatitis; acute pancreatitis has been reported.

  • Gastroparesis (slow stomach emptying)Do not use

    Not recommended in gastroparesis — further slowing of gastric emptying is expected.

  • Thyroid diseaseCaution

    Thyroid disease itself is not a contraindication, but thyroid cancer history must be clarified; thyroid medicine absorption can change as gastric emptying slows.

  • Pancreatic diseaseCaution

    Pancreatic disease warrants specialist assessment before considering any GLP-1 medicine.

  • Gallbladder diseaseCaution

    Cholelithiasis and cholecystitis occur more often with rapid weight loss and were more frequent in trials.

  • DiabetesCaution

    Hypoglycaemia risk rises with insulin or sulfonylureas; type 1 diabetes is outside the licence.

  • Diabetic retinopathy (eye disease)Caution

    Rapid glucose improvement was associated with worsening retinopathy in people with type 2 diabetes (SUSTAIN-6).

  • Kidney diseaseCaution

    Acute kidney injury has been reported, usually with dehydration from vomiting or diarrhoea.

  • Gastrointestinal diseaseCaution

    Not studied in severe gastrointestinal disease; slowed gastric emptying may worsen symptoms.

  • Mental health conditionCaution

    Weight-management labels advise monitoring for depression or suicidal thoughts; discuss any mental-health history.

  • Current or previous eating disorderCaution

    Appetite-suppressing medicines require specialist assessment where there is a current or previous eating disorder.

  • Cardiovascular diseaseCaution

    Resting heart rate increases by 1–4 bpm on average; arrhythmia history should be reviewed.

Do not use = should not be used · Caution = needs assessment

06 Interactions

Medicine classes that need review

Grouped by how seriously the combination should be taken. Class labels match the medicines questionnaire in the assessment.

  • Major
  • Moderate
  • Minor

Major

Combination should be reviewed by a prescriber before use.

  • Insulin

    Lantus, NovoRapid, Humalog, Tresiba

    Combined use increases hypoglycaemia risk; insulin doses are usually reduced under supervision.

  • Sulfonylurea

    Gliclazide, glimepiride, glipizide

    Combined use increases hypoglycaemia risk; sulfonylurea dose reduction is often needed.

  • GLP-1 / incretin medicine

    Ozempic, Wegovy, Mounjaro, Saxenda

    Should not be combined with another GLP-1 or GIP/GLP-1 medicine — duplicate mechanism with no safety data.

Moderate

Monitoring or dose review is usually advised.

  • Anticoagulant (blood thinner)

    Warfarin, apixaban, rivaroxaban

    Delayed gastric emptying can alter absorption; more frequent INR monitoring is recommended when starting or changing dose with warfarin.

  • Thyroid hormone

    Levothyroxine, liothyronine

    Levothyroxine exposure may change with slowed gastric emptying; thyroid function should be monitored.

  • Narrow-therapeutic-index medicine

    Lithium, digoxin, ciclosporin

    Medicines that depend on rapid absorption or have a narrow therapeutic window may need closer monitoring.

Minor

Generally compatible; awareness is sufficient.

  • Oral contraceptive

    Combined pill, progestogen-only pill

    No clinically relevant reduction shown for semaglutide (unlike tirzepatide), but vomiting can reduce pill effectiveness.

  • Other glucose-lowering medicine

    Metformin, SGLT2 inhibitors, DPP-4 inhibitors

    Generally compatible; glucose monitoring advised when combined.

07 Pregnancy & breastfeeding

Status in pregnancy

Not recommended

Not recommended in pregnancy or while breastfeeding. Because of its long half-life, labels advise stopping at least two months before a planned pregnancy.

08 Monitoring

What is usually monitored

Parameters that trials and product information track. A clinician decides what applies to an individual.

  1. 01Weight and BMI trend against the licensed eligibility criteria
  2. 02Gastrointestinal tolerability at every dose escalation
  3. 03Blood glucose if on insulin or sulfonylureas
  4. 04Thyroid function if on levothyroxine
  5. 05Hydration and kidney function during vomiting or diarrhoea
  6. 06Mood and mental health
  7. 07Muscle mass and protein intake during rapid weight loss

09 Combinations

What is known about combining it

Notes on pairing with other compounds in the directory: whether the combination has been studied in people, and where mechanisms overlap.

  • Tirzepatide

    No human studies

    Overlap · Both are incretin-based appetite and glucose medicines acting on GLP-1 receptors.

    Combining two incretin medicines duplicates mechanism, has no safety data and is outside every licence.

  • Liraglutide

    No human studies

    Overlap · Both are GLP-1 receptor agonists.

    Duplicate mechanism — never used together.

  • Retatrutide

    No human studies

    Overlap · Retatrutide already includes GLP-1 receptor activity.

    No rationale or data for combining with another GLP-1 medicine.

  • Cagrilintide

    Studied together in humans

    Overlap · Complementary appetite pathways (GLP-1 + amylin).

    The fixed combination CagriSema has been studied in phase 3 (REDEFINE 1), but the combination remains investigational and is not authorised.

  • CJC-1295

    No human studies

    No human studies of GLP-1 medicines combined with growth-hormone secretagogues.

  • Ipamorelin

    No human studies

    No human studies of GLP-1 medicines combined with growth-hormone secretagogues.

  • BPC-157

    No human studies

    No human data on this combination; BPC-157 itself lacks human efficacy data.

  • AOD-9604

    No human studies

    No human data on this combination.

  • Gonadorelin

    No human studies

    No human data on the combination. Weight loss with a GLP-1 medicine can itself raise testosterone in men with obesity, which complicates interpreting any gonadorelin effect.

Discuss any proposed combination with a qualified healthcare professional.

10 Source considerations

Supply, quality and legitimacy

How the compound reaches people in practice, and what that means for product quality.

  1. 01Prescription-only medicine in every major jurisdiction — legitimate supply requires a prescription from a licensed prescriber.
  2. 02Regulators (MHRA, FDA) have issued warnings about falsified and counterfeit 'Ozempic' pens and unregulated online sellers.
  3. 03Compounded or 'research-grade' semaglutide vials are not the authorised product and are not quality-assured to the same standard.

11 Questions for your clinician

Take these to your appointment

Specific to this compound. The personal assessment adds questions drawn from your own history and medicines.

  1. 01Do I meet the licensed eligibility criteria (BMI and weight-related conditions) in my country?
  2. 02How will my other medicines — especially diabetes medicines or blood thinners — be adjusted?
  3. 03What is the plan for dose escalation and for managing nausea?
  4. 04How will we protect muscle mass while I lose weight?
  5. 05What happens when treatment stops, and is there a maintenance plan?

The personal assessment tailors this list to your responses.

12 Alternatives

Compounds with stronger evidence or firmer regulatory footing

Listed for overlapping goals. Whether any is appropriate depends on your history — the assessment maps that for you.

13 References

Sources behind this record

Regulator documents and peer-reviewed publications used to derive every grade and statement above.

  1. 01Wilding JPH et al. STEP 1. NEJM 2021
  2. 02Garvey WT et al. STEP 5. Nat Med 2022
  3. 03Lincoff AM et al. SELECT. NEJM 2023
  4. 04Wegovy Summary of Product Characteristics (UK)
  5. 05Wegovy US Prescribing Information (FDA, Aug 2025)
  6. 06NICE TA875 — Semaglutide for managing overweight and obesity

The Peptide Checkup provides educational information and a structured summary of published research and regulatory status. It is not medical advice, does not diagnose or treat any condition, and does not replace a consultation with a qualified healthcare professional.

Personal assessment

Check Semaglutide against your history

Seven minutes of structured questions about your goal, history and medicines, mapped against this record by a deterministic, clinician-reviewable rules engine. The report tells you when not to buy.

Start the assessmentCompare with another