1. What Is CAG? A Complete Scientific Guide

   CAG is a synthetic, long-acting analogue of the human hormone amylin.

   It is being developed as an investigational treatment for overweight and obesity, both:

   • As a standalone compound

   • In combination with semaglutide

   The combination of CAG and semaglutide is commonly known by the development name:

   CagriSema

   CAG is not a GLP-1 receptor agonist.

   Instead, it is designed to reproduce and extend some of the biological actions of amylin, a peptide hormone normally released from pancreatic beta cells alongside insulin after food is consumed.

   Amylin contributes to the regulation of:

   • Fullness

   • Meal size

   • Gastric emptying

   • Glucagon secretion

   • Food intake

   • Body-weight regulation

   CAG has been modified to remain active for considerably longer than naturally occurring amylin, allowing it to be studied as a once-weekly treatment.

   Clinical trials have reported meaningful reductions in body weight when CAG is used alone. Larger reductions have been observed when it is coadministered with semaglutide.

   However, CAG remains investigational. It is not currently an authorised medicine in the United Kingdom, and ClinicalTrials.gov continues to describe it as a medicine that doctors may not yet prescribe.

   This guide examines what CAG is, how amylin signalling affects appetite, what clinical trials have shown and where important uncertainties remain.

   ---

CAG was engineered as a stable, lipidated and long-acting amylin analogue for obesity research.

What is CAG?

CAG is a chemically modified peptide designed to activate biological pathways associated with amylin.

Naturally occurring amylin has a relatively short duration of action and can form unstable molecular aggregates.

These properties make unmodified human amylin difficult to develop as a practical medicine.

CAG was designed to overcome these limitations through structural modifications that improve:

• Molecular stability

• Solubility

• Resistance to breakdown

• Duration of activity

• Suitability for once-weekly administration

It is sometimes informally shortened to:

Cagri

This nickname should not be confused with CagriSema, which refers specifically to the combination of CAG and semaglutide.

What is amylin?

Amylin is a naturally occurring peptide hormone produced primarily by pancreatic beta cells.

It is released alongside insulin following food intake.

While insulin helps regulate blood glucose by supporting glucose uptake and storage, amylin contributes to the coordination of the meal response through effects including:

• Increasing fullness

• Reducing meal size

• Slowing gastric emptying

• Suppressing inappropriate glucagon release

• Influencing appetite-related brain signalling

Amylin acts both through peripheral pathways and through areas of the brain involved in appetite and energy regulation.

Is amylin the same as insulin?

No.

Amylin and insulin are different hormones, although they are produced by the same pancreatic beta cells and released together after meals.

Insulin primarily regulates blood glucose by helping cells take up and store glucose.

Amylin helps coordinate the digestive and appetite response by influencing:

• Satiety

• Gastric emptying

• Glucagon

• Food intake

CAG does not replace insulin.

How was CAG developed?

The development of CAG involved modifying an amylin-related peptide to improve its pharmaceutical characteristics.

Researchers sought a molecule that would:

• Activate amylin-related receptors

• Avoid rapid degradation

• Remain soluble

• Resist aggregation

• Support once-weekly administration

• Produce sustained appetite and weight effects

Published development work describes CAG as a stable, lipidated, long-acting amylin analogue selected for clinical development in obesity.

How does CAG work?

CAG is believed to reduce food intake primarily by activating amylin-related receptor pathways.

Its proposed actions include:

• Increasing satiety

• Reducing hunger

• Reducing meal size

• Influencing food reward

• Slowing gastric emptying

• Modifying glucagon responses

These actions may reduce total energy intake and support gradual weight loss.

CAG does not directly burn body fat.

Weight reduction occurs largely because sustained appetite regulation can make it easier to consume less energy over time.

What are amylin receptors?

Amylin receptors are formed when a calcitonin receptor combines with a specialised receptor-activity-modifying protein.

These receptor complexes are commonly called:

• AMY1

• AMY2

• AMY3

Different receptor combinations occur in different tissues.

Amylin-related signalling has been identified in brain regions involved in:

• Satiety

• Nausea

• Reward

• Energy balance

• Meal termination

The exact contribution of each receptor subtype to CAG’s clinical effects remains under investigation.

CAG and the calcitonin receptor

CAG has activity within the broader calcitonin-family receptor system.

This family includes receptors associated with:

• Amylin

• Calcitonin

• Calcitonin gene-related peptide

• Adrenomedullin

These pathways overlap structurally but perform different physiological roles.

CAG should not be described simply as calcitonin or assumed to reproduce all the actions of calcitonin.

How does amylin influence appetite?

Amylin signals that food has been consumed and contributes to ending a meal.

It acts partly through the area postrema, a brainstem region involved in detecting signals circulating in the blood.

From there, signals are transmitted to additional appetite-regulating regions.

Amylin may influence both:

Eating driven by biological energy needs.

Eating driven by reward, pleasure, environmental cues or cravings rather than immediate energy requirements.

A scientific review of CAG development describes amylin as influencing both homeostatic and hedonic brain regions involved in satiety.

CAG and satiety

Satiety is the feeling of fullness that continues after a meal and reduces the desire to eat again.

CAG is designed to strengthen amylin-related satiety signalling over an extended period.

In practical terms, this may lead to:

• Feeling full sooner

• Remaining full for longer

• Reduced portion size

• Reduced spontaneous food intake

• Less interest in highly rewarding foods

Individual experiences may differ, and these effects should not be assumed to occur equally in everyone.

CAG and hunger

Hunger is regulated by a network involving:

• The brain

• Gastrointestinal hormones

• Nutrient signals

• Energy stores

• Sleep

• Stress

• Learned behaviour

CAG targets only part of this system.

It may reduce appetite-related signals, but it does not remove every psychological, environmental or behavioural driver of eating.

CAG and gastric emptying

Gastric emptying describes how quickly food moves from the stomach into the small intestine.

Naturally occurring amylin slows gastric emptying.

CAG may reproduce some of this effect, which can:

• Prolong fullness

• Alter post-meal glucose absorption

• Contribute to nausea

• Affect the timing of oral medicine absorption

The strength and persistence of this effect with long-term treatment require further characterisation.

CAG and glucagon

Glucagon is a hormone that raises blood glucose by signalling the liver to release stored glucose.

Amylin helps suppress inappropriate glucagon release following meals.

CAG may influence this pathway, although weight-management development has focused more heavily on appetite and body weight than on glucagon alone.

It should not be described as a replacement for established diabetes treatment.

Is CAG a GLP-1 receptor agonist?

No.

CAG is an amylin analogue.

GLP-1 receptor agonists include medicines such as:

• Semaglutide

• Liraglutide

• Dulaglutide

These activate the GLP-1 receptor.

CAG acts through amylin-related receptor pathways.

The two systems overlap in some effects, including:

• Reduced food intake

• Increased fullness

• Slower gastric emptying

• Weight reduction

However, they are chemically and pharmacologically distinct.

CAG vs semaglutide

CAG and semaglutide regulate appetite through different but complementary pathways.

Their different mechanisms are the basis for studying them together.

What is CagriSema?

CagriSema is the development name for coadministered:

• CAG

• Semaglutide

The two compounds are intended to influence separate appetite-regulating pathways.

The proposed rationale is that activating both:

• Amylin signalling

• GLP-1 signalling

may produce greater weight loss than targeting either pathway alone.

CagriSema has undergone phase III clinical trials in adults with overweight or obesity, including people with type 2 diabetes.

Is CagriSema one peptide?

No.

CagriSema is not a single hybrid peptide.

It refers to two separate active compounds administered together:

• CAG

• Semaglutide

They retain their distinct molecular identities and receptor targets.

CAG phase II weight-loss trial

A major phase II trial assessed once-weekly CAG in adults with overweight or obesity.

Participants received different CAG dose levels, liraglutide or placebo alongside lifestyle intervention.

At 26 weeks, CAG produced dose-dependent body-weight reductions.

The highest studied CAG dose produced an average reduction of approximately 10.8%, compared with approximately:

• 9.0% with daily liraglutide

• 3.0% with placebo

The trial concluded that CAG produced significant weight reduction and was generally well tolerated over the study period. It was funded by Novo Nordisk.

What does dose-dependent weight loss mean?

Dose dependent means that higher study doses were generally associated with greater average weight reduction.

This does not mean that increasing the amount indefinitely will continue to increase benefit.

At higher exposure levels:

• Adverse effects may become more common.

• Treatment discontinuation may increase.

• Additional benefit may become smaller.

• Safety limitations may outweigh weight effects.

Clinical dose selection requires balancing effectiveness and tolerability.

CAG and semaglutide phase Ib trial

An early phase Ib trial examined CAG coadministered with semaglutide.

At week 20, mean body-weight reductions in selected combination groups were approximately:

• 15.7% with CAG 1.2 mg plus semaglutide

• 17.1% with CAG 2.4 mg plus semaglutide

• 15.4% with CAG 4.5 mg plus semaglutide

The relevant placebo-plus-semaglutide comparison groups experienced smaller average reductions.

These early results supported further development of the CagriSema combination, but the study was short and included relatively small groups.

REDEFINE 1

REDEFINE 1 was a large phase III trial in adults with overweight or obesity without type 2 diabetes.

It compared:

• CAG plus semaglutide

• CAG alone

• Semaglutide alone

• Placebo

The 2025 publication concluded that coadministered CAG and semaglutide produced significant and clinically relevant weight reduction compared with placebo.

The trial also allowed direct comparison of the combination with its individual components.

REDEFINE 2

REDEFINE 2 studied adults with overweight or obesity and type 2 diabetes.

Once-weekly CAG plus semaglutide produced significantly greater weight reduction than placebo.

The results support effectiveness in a population that often experiences less weight loss from obesity medicines than people without type 2 diabetes.

East Asian phase III evidence

A phase IIIa trial published in 2026 evaluated CAG–semaglutide in East Asian adults with overweight or obesity, with or without type 2 diabetes.

The investigators reported findings supporting the combination’s efficacy and safety for weight management in the population studied.

This improves the geographical diversity of the evidence, although long-term and post-authorisation evidence will still be needed.

CAG in type 2 diabetes

CAG has been studied both alone and with semaglutide in people with type 2 diabetes.

A phase II trial published in 2023 assessed coadministered CAG and semaglutide in this population and examined:

• Body weight

• HbA1c

• Safety

• Tolerability

The research supported continued development of the combination, but CAG is not currently a routine approved diabetes medicine.

Does CAG lower blood glucose?

CAG may influence post-meal glucose regulation through:

• Slower gastric emptying

• Reduced food intake

• Glucagon suppression

• Weight reduction

However, its glucose-lowering profile is not identical to that of insulin or a GLP-1 receptor agonist.

When used with semaglutide, glucose effects cannot be attributed solely to CAG.

Does CAG cause hypoglycaemia?

Amylin analogues do not usually cause profound hypoglycaemia when used alone because they do not directly force insulin secretion in the same way as some diabetes medicines.

However, hypoglycaemia risk may increase when appetite-reducing compounds are combined with:

• Insulin

• Sulfonylureas

• Other glucose-lowering medicines

• Very low calorie intake

Clinical monitoring is particularly important in people with diabetes.

CAG and fat loss

Clinical trials measure total body-weight change rather than only fat loss.

Weight reduction may include changes in:

• Fat mass

• Lean mass

• Water

• Glycogen

• Gastrointestinal contents

The desired outcome in obesity treatment is primarily reduction of excess fat while preserving as much muscle and physical function as possible.

CAG should not be described as selectively removing fat without affecting lean tissue.

CAG and muscle loss

Any substantial weight loss can include some loss of lean mass.

The proportion depends on factors including:

• Protein intake

• Resistance training

• Age

• Rate of weight loss

• Baseline muscle mass

• Illness

• Total energy intake

There is insufficient evidence to claim that CAG completely prevents muscle loss.

Research registered in 2026 is also examining wider outcomes such as bone health during CAG-associated weight reduction.

CAG and food cravings

Amylin signalling may influence hedonic eating and food reward.

This creates a plausible mechanism through which CAG could reduce:

• Cravings

• Desire for high-energy foods

• Repeated snacking

• Reward-driven eating

Clinical trials have focused more strongly on body weight and appetite than on proving treatment of binge-eating or food-addiction disorders.

Does CAG increase metabolism?

CAG’s principal known effect is appetite regulation rather than a large direct increase in metabolic rate.

Weight reduction appears to arise mainly from reduced energy intake.

Claims that it substantially accelerates fat burning independent of diet are unsupported.

Does CAG suppress appetite more than semaglutide?

The compounds affect different pathways, and individual responses vary.

Clinical trials suggest that their combination can produce greater average weight reduction than either component alone.

That does not prove that CAG alone universally suppresses appetite more strongly than semaglutide.

CAG vs liraglutide

The phase II CAG trial included daily liraglutide as an active comparator.

At 26 weeks, higher-dose CAG produced greater average weight loss than the liraglutide group in that study.

However, comparisons across medicines depend on:

• Dose

• Trial length

• Participant population

• Adherence

• Lifestyle intervention

• Statistical design

This trial does not establish superiority over every GLP-1 medicine.

CAG vs TZ GLP1

TZ GLP1 activates:

• GIP receptors

• GLP-1 receptors

CAG activates amylin-related receptor pathways.

They have not been compared directly in a definitive head-to-head phase III trial.

Results from separate trials cannot be reliably used to declare one universally superior because the participant groups, methods and study durations differ.

CAG vs RT GLP3

RT GLP3 is an investigational triple agonist targeting:

• GLP-1

• GIP

• Glucagon receptors

CAG is an amylin analogue.

Both are being investigated for weight management, but their biological mechanisms are substantially different.

There is no definitive head-to-head clinical trial establishing which produces better long-term outcomes.

CAG vs pramlintide

Pramlintide is another synthetic amylin analogue.

CAG was designed for longer exposure and improved suitability for chronic weight-management research.

Why combine amylin with GLP-1?

The biological rationale is that amylin and GLP-1 provide partly overlapping but distinct signals.

GLP-1 receptor activation affects:

• Appetite

• Insulin secretion

• Glucagon

• Gastric emptying

Amylin-related signalling affects:

• Meal termination

• Satiety

• Food reward

• Gastric emptying

• Glucagon

Using both pathways may provide a broader appetite-regulation signal than either alone.

Is CAG approved?

No standalone CAG medicine is currently authorised for routine prescribing.

ClinicalTrials.gov entries in 2026 continue to describe CAG as an investigational medicine that doctors may not yet prescribe.

An EMA paediatric investigation plan concerns development requirements and does not represent marketing authorisation.

Is CagriSema approved?

At the time of writing, CagriSema remains an investigational combination rather than an authorised UK medicine.

Positive phase III trial results do not automatically mean that regulatory review has been completed or approval has been granted.

Marketing authorisation requires separate evaluation of:

• Quality

• Safety

• Effectiveness

• Manufacturing

• Risk management

• Product labelling

Is CAG available on prescription?

It is not currently available as a routine authorised prescription medicine in the United Kingdom.

Products sold online as CAG are not equivalent to participation in a regulated clinical trial.

They should not be described as approved pharmaceutical CAG.

CAG safety

The most frequently reported adverse effects in clinical research have involved the gastrointestinal system.

These commonly include:

• Nausea

• Vomiting

• Diarrhoea

• Constipation

• Abdominal discomfort

• Reduced appetite

These effects are consistent with amylin-related appetite and gastric signalling.

Most events in trials have been described as mild or moderate, but some participants discontinued treatment because of adverse effects.

Nausea

Nausea is one of the most important tolerability limitations for both amylin and GLP-1 pathways.

It may be related to:

• Brainstem receptor activation

• Slower gastric emptying

• Dose escalation

• Reduced meal tolerance

• Combination treatment

A compound can reduce appetite without nausea, but the biological pathways may overlap in some individuals.

Vomiting

Vomiting has occurred in CAG trials, particularly during dose escalation or combination treatment.

Repeated vomiting can cause:

• Dehydration

• Electrolyte disturbance

• Kidney stress

• Inability to tolerate oral medication

• Nutritional deficiency

Persistent vomiting requires medical assessment.

Constipation and diarrhoea

Changes in gastrointestinal motility may produce either constipation or diarrhoea.

The response can vary according to:

• Diet

• Fluid intake

• Other medicines

• Baseline bowel function

• Dose

• Treatment combination

Severe abdominal symptoms should not automatically be assumed to be a normal treatment effect.

CAG and pancreatitis

CAG’s relationship with pancreatitis has not been fully characterised.

Because abdominal pain, nausea and vomiting may have multiple causes, persistent or severe upper abdominal pain requires proper assessment.

Risk information from semaglutide-containing combination studies should not automatically be attributed entirely to CAG.

CAG and gallbladder disease

Rapid or substantial weight loss itself can increase the risk of gallstones.

This can occur regardless of which method caused the weight loss.

Possible warning signs include:

• Upper-right abdominal pain

• Pain after fatty meals

• Fever

• Jaundice

• Persistent vomiting

Longer-term studies are needed to characterise gallbladder risks with CAG alone and in combination.

CAG and gastroparesis

Gastroparesis is delayed stomach emptying in the absence of a physical blockage.

Because amylin pathways slow gastric emptying, CAG may be unsuitable or poorly tolerated in people with significant pre-existing gastric-motility disorders.

Symptoms can include:

• Early fullness

• Nausea

• Vomiting

• Abdominal bloating

• Unpredictable blood glucose

• Inability to tolerate meals

Formal safety recommendations will depend on future regulatory assessment.

CAG and dehydration

Reduced food intake, vomiting or diarrhoea can contribute to dehydration.

Dehydration may lead to:

• Dizziness

• Low blood pressure

• Kidney dysfunction

• Headache

• Weakness

• Electrolyte abnormalities

Risk may be higher in older adults and people taking diuretics.

CAG and kidney function

CAG is not established as directly toxic to the kidneys.

However, severe gastrointestinal adverse effects can reduce fluid intake or cause fluid loss, which may impair kidney function.

People with existing kidney disease may be more vulnerable to dehydration-related complications.

CAG and heart rate

Long-term cardiovascular effects remain under investigation.

Some appetite-regulating medicines influence:

• Heart rate

• Blood pressure

• Autonomic activity

Large cardiovascular-outcome research is necessary to establish whether weight-loss benefits translate into reduced cardiovascular events and whether any treatment-specific risks emerge.

REDEFINE 3 is designed as a long-duration outcomes study and is listed as lasting up to approximately four and a half years.

CAG and thyroid cancer

CAG is not a GLP-1 receptor agonist, so warnings associated with a semaglutide-containing combination cannot automatically be assigned to CAG alone.

However, long-term carcinogenicity and thyroid safety require formal regulatory review.

Claims that CAG has either no cancer risk or the same risk as semaglutide are premature.

Pregnancy and breastfeeding

Intentional weight-loss treatment is generally not appropriate during pregnancy.

Adequate evidence has not established CAG as safe during:

• Pregnancy

• Breastfeeding

• Attempts to conceive

Developmental and reproductive safety will require assessment before any regulatory approval.

CAG and fertility

CAG is not a fertility treatment.

Substantial weight loss may indirectly influence reproductive function in some people, but severe energy restriction or rapid weight loss may also disrupt:

• Menstrual cycles

• Ovulation

• Testosterone

• Sperm production

The effect depends on baseline health, nutrition and degree of weight loss.

CAG in children

CAG is not an established paediatric obesity medicine.

EMA records show that paediatric development plans have been considered for CAG and semaglutide, but these administrative development decisions do not establish approval or routine paediatric safety.

Children require age-specific evidence because growth, puberty, bone health and nutrition may be affected differently.

CAG and eating disorders

Appetite suppression may be dangerous in people with current or previous eating disorders.

Potential concerns include:

• Restrictive eating

• Malnutrition

• Compulsive weight monitoring

• Purging

• Body-image deterioration

• Relapse

Weight-loss research does not establish safety for anorexia nervosa, bulimia nervosa or other eating disorders.

CAG and oral medicines

Slower gastric emptying could potentially alter how quickly oral medicines are absorbed.

This may be particularly relevant for medicines requiring:

• Rapid onset

• Narrow therapeutic ranges

• Precise timing

• Reliable peak concentrations

Specific medicine-interaction guidance will depend on future pharmacology and regulatory data.

CAG with insulin

Combining CAG with insulin may require adjustment of diabetes management because:

• Food intake may fall.

• Gastric emptying may change.

• Glucagon responses may be altered.

• Weight and insulin requirements may decline.

Unadjusted insulin exposure could increase hypoglycaemia risk.

CAG with sulfonylureas

Sulfonylureas stimulate insulin release.

If food intake falls substantially while insulin secretion remains elevated, hypoglycaemia risk may increase.

Combination treatment requires clinical monitoring rather than assumptions based on CAG’s mechanism alone.

CAG with semaglutide

CAG and semaglutide have been intentionally studied together as CagriSema.

This does not mean that independently sourced products can safely reproduce the clinical-trial combination.

Important differences may include:

• Formulation

• Concentration

• Dose escalation

• Storage

• Injection device

• Product purity

• Medical monitoring

The phase III evidence relates to regulated investigational products used within controlled protocols.

CAG with TZ GLP1

There is insufficient controlled evidence establishing the safety of combining CAG with TZ GLP1.

Both can strongly reduce appetite and may affect gastrointestinal function.

Potential concerns could include:

• Severe nausea

• Vomiting

• Dehydration

• Excessive calorie restriction

• Malnutrition

• Loss of lean mass

• Medication-interaction difficulties

A combination being biologically plausible does not establish that it is safe.

CAG with RT GLP3

CAG and RT GLP3 have not been established as a clinically validated combination.

RT GLP3 already activates three metabolic receptors, while CAG adds a separate appetite-regulation pathway.

The combined effect on tolerability, nutrition and long-term safety is unknown.

Does CAG stop working?

Weight-loss responses may slow or plateau over time.

A plateau does not necessarily mean the biological effect has completely stopped.

As body weight falls:

• Energy expenditure declines.

• The body requires fewer calories.

• Hunger-regulation pathways adapt.

• The initial energy deficit becomes smaller.

Long-term maintenance and post-treatment evidence remain important research questions.

What happens after CAG is stopped?

Long-term discontinuation data remain limited.

With many appetite-regulating medicines, stopping treatment can allow:

• Hunger to return

• Satiety effects to weaken

• Energy intake to rise

• Weight regain to occur

Whether CAG produces a distinct post-treatment pattern requires longer follow-up.

Does CAG permanently reset appetite?

No evidence demonstrates that CAG permanently resets the appetite system.

Its effects depend on continued receptor activity while the compound is present and biologically active.

Lasting behavioural changes may help some people maintain weight loss, but a permanent pharmacological reset has not been proven.

Product-quality concerns

Products sold online as CAG may differ substantially from clinical-trial material.

Important quality variables include:

• Correct peptide sequence

• Correct molecular modifications

• Purity

• Concentration

• Sterility

• Endotoxin levels

• Counterion composition

• Aggregation

• Storage stability

• Degradation

CAG’s structure and long-acting modifications make identity testing more complex than confirming the approximate mass of a basic short peptide.

Analytical testing

HPLC can estimate purity and detect certain chemical impurities.

Mass spectrometry can support confirmation of molecular mass and identity.

Peptide mapping can provide additional evidence that the intended amino-acid structure is present.

Testing should confirm the presence and position of modifications used to extend biological activity.

Sterility testing evaluates contamination by living microorganisms.

Endotoxin testing assesses inflammatory bacterial components.

Stability testing examines whether the peptide remains chemically intact and accurately concentrated during storage.

No single test proves complete pharmaceutical quality.

WADA status

CAG is not generally classified as an anabolic agent.

However, athletes should not assume that an investigational peptide is permitted solely because it is not prominently named.

Anti-doping rules include broad categories involving:

• Peptide hormones

• Related substances

• Non-approved substances

• Compounds with similar biological effects

Competitive athletes should consult the current official Prohibited List and specialist anti-doping guidance.

Common CAG myths

Fact: CAG is a long-acting amylin analogue.

Fact: CagriSema combines CAG with semaglutide.

Fact: Its primary effect is appetite and satiety regulation, leading to lower energy intake.

Fact: Appetite reduction varies between individuals and is unlikely to represent a permanent reset.

Fact: It remains investigational and is not an authorised UK medicine.

Fact: Clinical trial success and marketing authorisation are separate processes.

Fact: They act through different receptor systems.

Fact: The risk may increase when it is combined with insulin or other glucose-lowering treatments.

Fact: Substantial weight loss generally includes some lean mass and other tissue changes.

Fact: Identity, concentration, purity, formulation and sterility may differ.

Frequently asked questions

Yes. CAG is a synthetic long-acting peptide analogue of amylin.

It is a synthetic analogue of the naturally occurring peptide hormone amylin.

No.

It activates amylin-related receptor systems formed from calcitonin receptors and receptor-activity-modifying proteins.

It is being researched for increasing satiety, reducing food intake and supporting weight loss.

Clinical weight-loss results and amylin biology support an appetite-reducing effect.

It may influence food-reward pathways, but individual responses vary and dedicated craving evidence remains limited.

Amylin signalling slows gastric emptying, and CAG may reproduce this effect.

It may influence glucose regulation indirectly, but it is not insulin and is not an approved standalone diabetes medicine.

It is not primarily an insulin-secretagogue medicine.

Its main known action is reducing food intake rather than substantially increasing metabolic rate.

It supports weight reduction mainly through appetite regulation rather than directly burning fat.

At 26 weeks, the highest studied CAG dose produced an average weight reduction of approximately 10.8%, compared with about 3% for placebo.

CagriSema is CAG coadministered with semaglutide.

No. It consists of two separate active compounds.

Phase III evidence indicates greater average weight reduction with the combination than with placebo and supports benefit beyond the individual components in the studied populations.

No standalone CAG medicine is currently authorised for routine prescribing.

No. It remains investigational at the time of writing.

It is not currently available as a routine authorised prescription medicine.

No. Both are amylin analogues, but CAG is longer acting and was developed specifically for once-weekly obesity treatment.

No.

No. TZ GLP1 is a GIP and GLP-1 receptor agonist.

No. RT GLP3 is an investigational GLP-1, GIP and glucagon receptor agonist.

The combination has been studied extensively as CagriSema, but trial results relate to controlled pharmaceutical products and protocols.

Controlled safety evidence is insufficient.

This is not an established or clinically validated combination.

Common research adverse effects include nausea, vomiting, diarrhoea, constipation and abdominal discomfort.

Yes.

Yes.

Yes.

Yes.

Vomiting, diarrhoea or substantially reduced intake may cause dehydration.

The risk may increase when it is combined with insulin or certain other diabetes medicines.

The relationship remains incompletely characterised. Severe persistent abdominal pain requires medical assessment.

Substantial weight loss itself can increase gallstone risk.

It may slow gastric emptying and could worsen symptoms in people with significant gastric-motility disorders.

Potentially. Slower gastric emptying may alter the timing of oral medicine absorption.

Safety has not been established, and intentional weight-loss treatment is generally inappropriate during pregnancy.

Adequate safety evidence is lacking.

It is not an established paediatric medicine.

It has not been proven to prevent all lean-mass loss during weight reduction.

This remains under investigation, including in a registered study examining bone health during weight loss.

Weight loss may plateau as the body adapts and energy requirements fall.

Long-term discontinuation data are limited, but appetite may return and weight regain may occur.

A recognised addiction or physical-dependence syndrome has not been established.

A specific withdrawal syndrome has not been established.

Long-term safety and cardiovascular-outcome evidence remain under investigation.

Athletes should consult the current official list and specialist guidance because investigational peptides may fall within broad prohibited categories.

No. Identity, purity, sterility, formulation and concentration cannot be assumed to be equivalent.

CAG research in context

Clinical evidence supports that CAG can produce meaningful average weight reduction in adults with overweight or obesity.

The phase II standalone trial showed dose-dependent weight loss, with higher studied doses producing greater average reductions than placebo.

Coadministration with semaglutide produces greater weight reduction than placebo and appears to provide additional benefit beyond using either pathway alone.

This has now been demonstrated across phase III programmes involving:

• Adults without type 2 diabetes

• Adults with type 2 diabetes

• East Asian populations

Researchers have not yet fully established:

• Long-term cardiovascular outcomes

• Long-term weight maintenance

• Outcomes after treatment discontinuation

• Long-term bone and muscle effects

• Safety during pregnancy

• Paediatric safety

• Optimal use alongside other obesity medicines

• Long-term cancer risk

• Effects in severe gastrointestinal disease

• Whether standalone CAG will obtain approval

• Whether all online products accurately contain CAG

Stronger long-term evidence requires:

• Cardiovascular-outcome trials

• Longer follow-up

• Post-treatment observation

• Detailed body-composition assessment

• Bone-health assessment

• Reproductive-safety studies

• Broader population diversity

• Real-world pharmacovigilance after any future approval

Key takeaways

CAG is a synthetic, long-acting analogue of the naturally occurring hormone amylin.

It is not a GLP-1 receptor agonist.

Its proposed effects include:

• Increased satiety

• Reduced hunger

• Smaller meal size

• Reduced food intake

• Slower gastric emptying

• Altered food-reward signalling

A phase II trial reported dose-dependent weight reduction, with the highest studied CAG dose producing an average loss of approximately 10.8% at 26 weeks.

CAG is also being developed with semaglutide under the name CagriSema.

Phase III trials have demonstrated substantial weight reduction with CagriSema in people with and without type 2 diabetes.

Common adverse effects involve the gastrointestinal system and include:

• Nausea

• Vomiting

• Diarrhoea

• Constipation

• Abdominal discomfort

CAG and CagriSema remain investigational and are not currently authorised UK medicines.

Positive trial results should not be confused with regulatory approval.

Commercially sourced research products should not be assumed to match the identity, quality, formulation or sterility of the regulated products used in clinical trials.

Glossary

Amylin: A pancreatic peptide hormone released alongside insulin that influences satiety, gastric emptying and glucagon.

Amylin analogue: A synthetic compound designed to reproduce some of amylin’s biological effects.

AMY receptor: A receptor complex formed from a calcitonin receptor and a receptor-activity-modifying protein.

CagriSema: The investigational combination of CAG and semaglutide.

Calcitonin receptor: A G-protein-coupled receptor that can form amylin receptors when combined with receptor-activity-modifying proteins.

Gastric emptying: Movement of food from the stomach into the small intestine.

Glucagon: A pancreatic hormone that raises blood glucose.

GLP-1: Glucagon-like peptide-1, an intestinal hormone involved in appetite and glucose regulation.

Hedonic eating: Food intake driven by pleasure or reward rather than immediate energy needs.

Homeostatic eating: Food intake driven primarily by biological energy requirements.

Hypoglycaemia: Abnormally low blood glucose.

Lipidation: Chemical attachment of a fatty-acid-related structure to extend a peptide’s duration of action.

RAMP: Receptor-activity-modifying protein, which combines with certain receptors to alter their function.

Satiety: The feeling of fullness that reduces the desire to continue or resume eating.

This article is provided for educational purposes only.

It is not intended to diagnose, treat or prevent disease or to replace advice from a qualified healthcare professional.

CAG is an investigational long-acting amylin analogue. It is not currently an authorised medicine in the United Kingdom.

Although clinical trials have reported meaningful body-weight reductions with CAG alone and larger reductions when combined with semaglutide, important uncertainties remain regarding long-term safety, cardiovascular outcomes, treatment discontinuation, muscle and bone effects and use in special populations.

Research products sold as CAG should not be assumed to reproduce the identity, quality, formulation, concentration or sterility of the investigational pharmaceutical products used in controlled clinical trials