Semaglutide
Metabolic
ABOUT
Semaglutide is a GLP-1 receptor agonist marketed in different formulations and brands. Approved indications, formulations, and safety information are product- and jurisdiction-specific.
EVIDENCE OVERVIEW
Supported by controlled human trials
WHAT THIS MEANS
Established. Review the research and limitations before relying on this record.
IDENTITY
HALF-LIFE
HOW IT IS THOUGHT TO WORK
Semaglutide is an acylated GLP-1 receptor agonist with 94% sequence homology to native GLP-1. Substitution at position 8 blocks DPP-4 degradation and a C18 fatty-diacid chain via a linker binds albumin, which together produce the once-weekly profile. It increases glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying and reduces appetite through central GLP-1 receptors.
PHARMACOKINETICS
Half-life approximately one week, with steady state reached in 4 to 5 weeks of once-weekly dosing. Absolute bioavailability after subcutaneous injection is high; elimination is by proteolytic cleavage and beta-oxidation of the fatty-acid side chain, with excretion in urine and faeces. The one-week half-life is why dose escalation is gradual and why effects persist for weeks after stopping.
REVIEW
PUBLISHED PAIR RECORDS
with Tirzepatide
Prescription GLP-1 coadministration is not recommendedTirzepatide product labelling states that coadministration with another GLP-1 receptor agonist is not recommended. This is prescription-product guidance, not a conclusion about every preparation or an individual treatment plan; a prescriber or pharmacist should review any intended combination.
Reviewed 19 Aug 2026with Retatrutide
Overlapping GLP-1 receptor activitySemaglutide and investigational retatrutide both include GLP-1 receptor activity. No curated direct combination study was identified. This is a mechanism overlap, not proof of a specific clinical outcome; it should be reviewed with a clinician or pharmacist rather than self-directed.
Reviewed 19 Aug 2026with Cagrilintide
Directly studied co-administration (CagriSema)Cagrilintide plus semaglutide has been studied as a fixed-dose investigational combination in randomised clinical trials. This is evidence that the exact pair has been co-administered under trial monitoring; it is not a general instruction to combine independently sourced products or a safety conclusion for other preparations.
Reviewed 19 Aug 2026with Native GIP
Direct native-GIP plus semaglutide studyA small randomised trial studied native GIP with semaglutide in people with type 2 diabetes. The prespecified glucose outcome was not improved by the added native GIP. This does not establish how other GIP/GLP-1 products, doses, routes, or formulations behave together.
Reviewed 19 Aug 2026with Survodutide
Overlapping incretin-pathway activitySemaglutide and Survodutide both act on incretin or amylin-family receptor pathways involved in glycaemic control, appetite and gastric emptying. Approved GLP-1 product labelling states that coadministration with another GLP-1 receptor agonist is not recommended, that these agents delay gastric emptying and may affect absorption of concomitantly administered oral medicines, and that combination with insulin or an insulin secretagogue increases hypoglycaemia risk. One member of this pair is an approved prescription product carrying that labelling; the other is investigational, so its combination data are incomplete. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 19 Aug 2026with Mazdutide
Overlapping incretin-pathway activitySemaglutide and Mazdutide both act on incretin or amylin-family receptor pathways involved in glycaemic control, appetite and gastric emptying. Approved GLP-1 product labelling states that coadministration with another GLP-1 receptor agonist is not recommended, that these agents delay gastric emptying and may affect absorption of concomitantly administered oral medicines, and that combination with insulin or an insulin secretagogue increases hypoglycaemia risk. One member of this pair is an approved prescription product carrying that labelling; the other is investigational, so its combination data are incomplete. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 19 Aug 2026with MK-677
Opposing effects on glucose regulationMK-677 raises growth-hormone exposure, and growth hormone is a counter-regulatory hormone: controlled human studies show GH administration impairs insulin-stimulated glucose uptake and deteriorates glucose tolerance through increased lipolysis, with chronic GH excess producing insulin resistance. Semaglutide acts in the opposite direction on glycaemic control. Trials of the oral secretagogue MK-677 specifically report raised fasting glucose and impaired glucose tolerance. The combined effect on blood glucose is therefore not predictable from either agent alone and warrants monitoring rather than assumption. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 19 Aug 2026with Tesamorelin
Opposing effects on glucose regulationTesamorelin raises growth-hormone exposure, and growth hormone is a counter-regulatory hormone: controlled human studies show GH administration impairs insulin-stimulated glucose uptake and deteriorates glucose tolerance through increased lipolysis, with chronic GH excess producing insulin resistance. Semaglutide acts in the opposite direction on glycaemic control. Trials of the oral secretagogue MK-677 specifically report raised fasting glucose and impaired glucose tolerance. The combined effect on blood glucose is therefore not predictable from either agent alone and warrants monitoring rather than assumption. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 19 Aug 2026with CJC-1295 with DAC
Opposing effects on glucose regulationCJC-1295 with DAC raises growth-hormone exposure, and growth hormone is a counter-regulatory hormone: controlled human studies show GH administration impairs insulin-stimulated glucose uptake and deteriorates glucose tolerance through increased lipolysis, with chronic GH excess producing insulin resistance. Semaglutide acts in the opposite direction on glycaemic control. Trials of the oral secretagogue MK-677 specifically report raised fasting glucose and impaired glucose tolerance. The combined effect on blood glucose is therefore not predictable from either agent alone and warrants monitoring rather than assumption. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 19 Aug 2026with Sermorelin
Opposing effects on glucose regulationSermorelin raises growth-hormone exposure, and growth hormone is a counter-regulatory hormone: controlled human studies show GH administration impairs insulin-stimulated glucose uptake and deteriorates glucose tolerance through increased lipolysis, with chronic GH excess producing insulin resistance. Semaglutide acts in the opposite direction on glycaemic control. Trials of the oral secretagogue MK-677 specifically report raised fasting glucose and impaired glucose tolerance. The combined effect on blood glucose is therefore not predictable from either agent alone and warrants monitoring rather than assumption. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 19 Aug 2026with Ipamorelin
Opposing effects on glucose regulationIpamorelin raises growth-hormone exposure, and growth hormone is a counter-regulatory hormone: controlled human studies show GH administration impairs insulin-stimulated glucose uptake and deteriorates glucose tolerance through increased lipolysis, with chronic GH excess producing insulin resistance. Semaglutide acts in the opposite direction on glycaemic control. Trials of the oral secretagogue MK-677 specifically report raised fasting glucose and impaired glucose tolerance. The combined effect on blood glucose is therefore not predictable from either agent alone and warrants monitoring rather than assumption. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 19 Aug 2026with PT-141
Additive delay of gastric emptyingBremelanotide (PT-141) labelling states that it slows gastric emptying and may reduce the rate and extent of absorption of concomitantly administered oral medicines - patients are advised to avoid it alongside oral drugs that depend on threshold concentrations, and to avoid oral naltrexone products entirely because exposure is significantly decreased. Approved GLP-1 labelling carries the same gastric-emptying caution. Scheduling Semaglutide alongside PT-141 therefore stacks two agents that independently delay gastric emptying, which matters most for any oral medicine taken in the same window. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 19 Aug 2026with Liraglutide
Overlapping incretin-pathway activityLiraglutide and Semaglutide both act on incretin or amylin-family receptor pathways involved in glycaemic control, appetite and gastric emptying. Approved GLP-1 product labelling states that coadministration with another GLP-1 receptor agonist is not recommended, that these agents delay gastric emptying and may affect absorption of concomitantly administered oral medicines, and that combination with insulin or an insulin secretagogue increases hypoglycaemia risk. Both members of this pair are approved prescription products carrying that labelling. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 21 Aug 2026with Exenatide
Overlapping incretin-pathway activityExenatide and Semaglutide both act on incretin or amylin-family receptor pathways involved in glycaemic control, appetite and gastric emptying. Approved GLP-1 product labelling states that coadministration with another GLP-1 receptor agonist is not recommended, that these agents delay gastric emptying and may affect absorption of concomitantly administered oral medicines, and that combination with insulin or an insulin secretagogue increases hypoglycaemia risk. Both members of this pair are approved prescription products carrying that labelling. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 21 Aug 2026with Dulaglutide
Overlapping incretin-pathway activityDulaglutide and Semaglutide both act on incretin or amylin-family receptor pathways involved in glycaemic control, appetite and gastric emptying. Approved GLP-1 product labelling states that coadministration with another GLP-1 receptor agonist is not recommended, that these agents delay gastric emptying and may affect absorption of concomitantly administered oral medicines, and that combination with insulin or an insulin secretagogue increases hypoglycaemia risk. Both members of this pair are approved prescription products carrying that labelling. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 21 Aug 2026with Pramlintide
Labelled caution: two agents that slow gastric emptyingPramlintide labelling states that it slows gastric emptying, that it is not recommended for patients taking other drugs that alter gastrointestinal motility, and that concomitant oral medicines whose effect depends on a threshold concentration should be taken at least 1 hour before or 2 hours after injection. Semaglutide carries its own labelled statement that it delays gastric emptying and may affect the absorption of concomitantly administered oral medicines. This is therefore not an inference from shared mechanism - each product's own labelling describes the effect the other also produces. Pramlintide additionally carries a boxed warning for severe hypoglycaemia when used with insulin, and GLP-1 labelling records increased hypoglycaemia risk in combination with insulin or an insulin secretagogue. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 21 Aug 2026with Teduglutide
Opposing effects on intestinal absorptionTeduglutide is a GLP-2 analogue that increases villus height and crypt depth, enlarging absorptive surface area; its labelling records a potential for increased absorption of concomitant oral medicines and advises monitoring where a drug is titrated or has a narrow therapeutic index, since the oral drug may need its dose reduced. Semaglutide works in the opposite direction on the same variable - incretin-pathway labelling and pharmacology describe delayed gastric emptying, which slows the rate at which an oral medicine reaches the small intestine. One agent is enlarging the absorptive surface while the other is changing the timing of delivery to it, so the net effect on any co-administered oral medicine is not predictable from either alone. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 21 Aug 2026with Larazotide acetate
Delayed gastric emptying may alter delivery of an enteric-coated oralSemaglutide labelling states that it delays gastric emptying and may affect the rate and extent of absorption of concomitantly administered oral medicines. Larazotide acetate is given as an enteric-coated oral capsule designed to release in the small intestine, acts locally on tight junctions there, and is minimally absorbed systemically - so what matters for it is where and when the capsule arrives, not a plasma concentration. Changing gastric emptying changes that delivery. Larazotide's own confirmatory phase 3 trial was stopped at interim analysis for futility, so there is no established effect size for it to lose in the first place; the interaction concern is about delivery, not about diminishing a proven benefit. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 21 Aug 2026with Kyinsu
Same substance taken twice: blend already contains this compoundKyinsu already contains Semaglutide at 1 mg per fixed-ratio unit per vial. Scheduling the standalone compound alongside the blend means taking it twice from two sources, and the blend's other components come with it whether or not they are wanted at that moment. This is the one exposure risk a blend creates that its individual parts do not, and it is arithmetic rather than pharmacology - the combined amount is whatever the two products add up to. Where a blend's ratio is fixed by the manufacturer, the only way to change one component's dose is to add or remove the whole vial. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 25 Aug 2026with CagriSema
Same substance taken twice: blend already contains this compoundCagriSema already contains Semaglutide at 2.4 mg per vial. Scheduling the standalone compound alongside the blend means taking it twice from two sources, and the blend's other components come with it whether or not they are wanted at that moment. This is the one exposure risk a blend creates that its individual parts do not, and it is arithmetic rather than pharmacology - the combined amount is whatever the two products add up to. Where a blend's ratio is fixed by the manufacturer, the only way to change one component's dose is to add or remove the whole vial. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 25 Aug 2026with CJC-1295 / Ipamorelin blend
Inherited from a component of this blendCJC-1295 / Ipamorelin blend contains Ipamorelin, and the catalogue holds a curated pair record between that component and Semaglutide: Ipamorelin (opposing effects on glucose regulation). Taking the blend therefore carries the same consideration as taking that component on its own, with the difference that a fixed-ratio vial cannot be adjusted independently of the rest of its contents. The evidence and citations here are the component record's; nothing has been studied about the blend itself. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 25 Aug 2026with CJC-1295 with DAC / Ipamorelin blend
Inherited from a component of this blendCJC-1295 with DAC / Ipamorelin blend contains CJC-1295 with DAC and Ipamorelin, and the catalogue holds a curated pair record between those components and Semaglutide: CJC-1295 with DAC (opposing effects on glucose regulation); Ipamorelin (opposing effects on glucose regulation). Taking the blend therefore carries the same consideration as taking that component on its own, with the difference that a fixed-ratio vial cannot be adjusted independently of the rest of its contents. The evidence and citations here are the component record's; nothing has been studied about the blend itself. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 25 Aug 2026with Sermorelin / Ipamorelin blend
Inherited from a component of this blendSermorelin / Ipamorelin blend contains Sermorelin and Ipamorelin, and the catalogue holds a curated pair record between those components and Semaglutide: Sermorelin (opposing effects on glucose regulation); Ipamorelin (opposing effects on glucose regulation). Taking the blend therefore carries the same consideration as taking that component on its own, with the difference that a fixed-ratio vial cannot be adjusted independently of the rest of its contents. The evidence and citations here are the component record's; nothing has been studied about the blend itself. Peppy reports curated pharmacology, not a safety verdict. A prescriber or pharmacist should review any intended combination.
Reviewed 25 Aug 2026with Lixisenatide
Overlapping GLP-1 receptor activityLixisenatide and semaglutide are both GLP-1 receptor agonists. Their labels document class gastrointestinal effects and altered gastric emptying, but Peppy did not identify a direct combination study for this pair. Shared receptor activity is a reason for clinician or pharmacist review, not evidence that the combination is safe or effective.
Reviewed 8 Oct 2026with Amycretin
Investigational GLP-1 activity overlaps with semaglutideAmycretin is an investigational GLP-1 and amylin receptor agonist, while semaglutide is a GLP-1 receptor agonist. The amycretin trial establishes its receptor profile; no direct coadministration study for this pair was identified. This is a pathway overlap only, not evidence of a specific outcome or of safe use together.
Reviewed 8 Oct 2026with Pemvidutide
Investigational GLP-1 activity overlaps with semaglutidePemvidutide is an investigational GLP-1/glucagon dual-receptor agonist and semaglutide is a GLP-1 receptor agonist. Human pemvidutide trials establish the GLP-1 component, but Peppy did not identify a direct study of this pair. The finding flags pathway overlap for professional review; it is not a dosing or safety conclusion.
Reviewed 8 Oct 2026HUMAN EVIDENCE
FDA-approved for chronic weight management (Wegovy) and type 2 diabetes (Ozempic, and orally as Rybelsus). The STEP programme established mean weight reductions of roughly 15% at 68 weeks against placebo in adults with obesity. SELECT extended the evidence to a hard outcome: in adults with cardiovascular disease and overweight or obesity but without diabetes, semaglutide reduced major adverse cardiovascular events. Both indications are supported by large randomised trials, which is what distinguishes this record from most others in this catalogue.
REPORTED EFFECTS
Boxed warning for risk of thyroid C-cell tumours based on rodent findings; contraindicated in personal or family history of medullary thyroid carcinoma or MEN 2. The most common adverse reactions are gastrointestinal - nausea, diarrhoea, vomiting, constipation, abdominal pain - and are dose-related and most pronounced during escalation. Labelled warnings include pancreatitis, gallbladder disease, acute kidney injury from volume depletion, diabetic retinopathy complications, and hypoglycaemia when combined with insulin or a sulfonylurea. Compounded semaglutide is not the approved product and has been the subject of FDA warnings about dosing errors.
RESEARCH LIMITATIONS
This is a label-based identity summary, not a recommendation. Check the current official label for the exact product and consult a qualified clinician before making treatment decisions.
CURATED SOURCES · 2