Metabolic peptide FAQ hub

Tirzepatide is a dual GIP/GLP-1 receptor agonist, meaning it activates both the GIP and GLP-1 incretin receptors simultaneously, whereas older agents such as semaglutide or liraglutide act only on the GLP-1 receptor. This dual mechanism appears to produce substantially greater reductions in body weight and blood glucose than GLP-1 monoagonism alone, as demonstrated in the head-to-head SURPASS-2 trial and confirmed by the magnitude of weight loss in the SURMOUNT programme.

Yes. Tirzepatide (Mounjaro) is an MHRA-licensed prescription medicine in the UK approved for type 2 diabetes management and chronic weight management. It is available through NHS prescribing pathways and private clinics. It is a prescription-only medicine and cannot legally be supplied without a valid UK prescription from a qualified prescriber. Research-grade tirzepatide is separately available for legitimate preclinical research under appropriate governance.

In SURMOUNT-1, the pivotal 72-week randomised controlled trial in adults without type 2 diabetes, participants receiving the 15 mg maintenance dose achieved a mean weight reduction of approximately 22.5% from baseline. This is approximately twice the weight loss typically observed with semaglutide 2.4 mg (Wegovy) in comparable populations and represents the largest pharmacologically induced weight reduction reported in any registered clinical trial at the time of publication.

In SURMOUNT and SURPASS trial populations, the most frequently reported adverse events were gastrointestinal in nature: nausea (reported by approximately 17–25% at higher doses), diarrhoea (12–17%), constipation (11–13%), and vomiting (6–10%). These effects are most pronounced during dose-escalation phases and typically attenuate with continued treatment. The slow titration schedule used in the trials is specifically designed to improve gastrointestinal tolerability.

The enhanced efficacy is attributed to the combined and potentially synergistic activation of both GIP and GLP-1 receptors. GIP receptor activation in adipose tissue and the central nervous system adds appetite-suppressing and energy-partitioning effects that complement those of GLP-1 receptor agonism. Additionally, GIP receptor co-activation may sensitise adipose tissue to the lipolytic actions of GLP-1 signalling. The net result is a greater reduction in ad libitum energy intake and a more favourable fat-to-lean mass loss ratio than observed with GLP-1 monoagonists.

The SURPASS-CVOT trial and cardiometabolic biomarker data from SURMOUNT trials have demonstrated reductions in established cardiovascular risk markers including systolic blood pressure, triglycerides, LDL-cholesterol, and waist circumference. The SELECT trial framework applied to semaglutide established a precedent for pharmacological weight-management agents reducing hard cardiovascular events, and tirzepatide's SURPASS-CVOT data have shown consistent directional trends supporting cardiovascular risk reduction.

Active clinical research is investigating tirzepatide in several additional contexts: SURMOUNT-OSA examined obstructive sleep apnoea severity; early-phase hepatology studies are assessing liver fat reduction and NASH histological improvement; and the SUMMIT trial is investigating its effects in heart failure with preserved ejection fraction. These exploratory programmes reflect the broad metabolic and organ-protective implications of dual incretin receptor agonism.

Tirzepatide is a licensed prescription medicine under the Human Medicines Regulations 2012. For legitimate preclinical or in vitro research, research-grade tirzepatide peptide may be procured through specialist research chemical suppliers subject to appropriate institutional governance. Its supply for unlicensed human use outside of a prescribing pathway is prohibited. Any research programme involving human participants requires full ethical approval and appropriate regulatory authorisation.

Retatrutide adds glucagon receptor agonism to the GIP and GLP-1 receptor agonism that defines tirzepatide. The glucagon component is hypothesised to increase basal energy expenditure and thermogenesis—mechanisms that complement the appetite suppression and incretin effects of GIP/GLP-1 agonism. Phase 2 data suggest this triple mechanism produces approximately 1.5–2 additional percentage points of weight loss versus tirzepatide at comparable timepoints, though direct head-to-head data are not yet available from Phase 3.

In the Phase 2 NEJM 2023 trial, participants with obesity receiving 12 mg retatrutide weekly achieved a mean body-weight reduction of approximately 24.2% at 48 weeks. Crucially, the weight-loss trajectory had not plateaued by Week 48 in the highest-dose group, suggesting that longer treatment might yield further reductions. This represents the largest pharmacologically induced weight-loss result published in a human clinical trial as of 2026.

No. Retatrutide is not approved by the MHRA or any regulatory authority as of May 2026. It remains an investigational new drug undergoing Phase 3 TRIUMPH trials. It is not legally available outside of authorised clinical research settings in the UK. Procurement through unregulated channels would contravene the Human Medicines Regulations 2012 and carries significant safety risks given incomplete Phase 3 characterisation.

Glucagon is a catabolic hormone that promotes hepatic lipid oxidation, glycogenolysis, and thermogenesis. Its receptor agonism is included to increase basal energy expenditure—a mechanism absent from GLP-1 and GIP agonism, which primarily reduce energy intake. Preclinical research demonstrated additive weight-loss effects when glucagon agonism was combined with dual GIP/GLP-1 agonism. The principal design challenge was calibrating the glucagon component to provide energy expenditure benefits without inducing significant hyperglycaemia.

The Phase 2 safety profile was broadly similar to other incretin-class agents: the most common adverse events were gastrointestinal (nausea, vomiting, diarrhoea, constipation), predominantly during dose-escalation phases. The glucagon receptor component introduces theoretical concerns around transient hyperglycaemia and hepatic effects that require monitoring. Full characterisation of the long-term safety profile awaits Phase 3 data. The thyroid C-cell class warning applicable to GLP-1 receptor agonists is also applicable.

Phase 3 TRIUMPH trials commenced in 2023 with primary endpoints at 72 weeks. Based on typical regulatory timelines, a New Drug Application or marketing authorisation application to the FDA, EMA, and MHRA might be submitted in 2025–2026, with potential approval decisions in 2026–2027, subject to trial results and regulatory review timelines. These projections are inherently uncertain.

This remains an active area of research. Preclinical data indicate that the glucagon receptor component increases basal metabolic rate through thermogenesis in brown adipose tissue and increased hepatic lipid oxidation. Human mechanistic substudies from the Phase 2 programme using indirect calorimetry are expected to quantify any increase in resting energy expenditure, which would distinguish retatrutide's mechanism from the predominantly food-intake-reducing mechanism of GLP-1 monoagonists.

Semaglutide is a synthetic GLP-1 receptor agonist that mimics the action of the endogenous gut hormone glucagon-like peptide-1. It reduces body weight primarily through central appetite suppression in the hypothalamus, which reduces ad libitum energy intake by approximately 35%. It also delays gastric emptying, stimulates glucose-dependent insulin secretion, and suppresses glucagon. The modifications to its structure—particularly the C-18 fatty diacid chain—extend its half-life to approximately seven days, enabling once-weekly dosing.

Semaglutide (Ozempic) is available on NHS prescription for type 2 diabetes. Wegovy (semaglutide 2.4 mg) for weight management has been subject to restricted NHS availability and is being phased into NHS specialist weight management services from 2024 onwards under NICE guidance TA875. Rybelsus (oral semaglutide) is also NHS-listed for type 2 diabetes. Availability through private prescribers is more immediate. All forms require a valid prescription.

Head-to-head data from SURPASS-2 demonstrate that tirzepatide 15 mg produces greater weight loss (approximately −11.2 kg) than semaglutide 1 mg (approximately −5.7 kg) in type 2 diabetes populations. Indirect comparisons between STEP 1 (semaglutide 2.4 mg, −14.9%) and SURMOUNT-1 (tirzepatide 15 mg, −22.5%) in non-diabetic obesity populations consistently favour tirzepatide, though these comparisons are limited by the absence of a direct head-to-head trial at weight-management doses.

The SELECT trial (2023) demonstrated a statistically significant 20% relative reduction in MACE (cardiovascular death, non-fatal MI, non-fatal stroke) in 17,604 adults with obesity and cardiovascular disease but no diabetes over a median 34.2 months. SUSTAIN-6 demonstrated cardiovascular superiority in type 2 diabetes. The FLOW trial (2024) demonstrated 24% reduction in the composite kidney outcomes endpoint. Collectively, these data represent the strongest cardiovascular and end-organ evidence base for any metabolic peptide.

The most clinically significant risks in trial populations were: gastrointestinal adverse events (nausea, vomiting, diarrhoea, constipation) in 40–50% of participants during dose escalation; gallbladder disease related to rapid weight loss; and diabetic retinopathy complications with rapid glycaemic improvement (particularly in SUSTAIN-6). Acute pancreatitis was reported at low rates without a significant difference from placebo. The thyroid C-cell warning applies across the GLP-1 receptor agonist class.

Yes. Semaglutide is under investigation for Parkinson's disease (a Phase 2 trial in the UK reported in 2024 showed slowed motor score deterioration) and Alzheimer's disease, based on preclinical evidence of neuroprotective GLP-1 receptor effects and epidemiological observations of reduced dementia rates in GLP-1 receptor agonist-treated populations. Additionally, the association between semaglutide use and reduced rates of substance use disorder is under mechanistic investigation.

Demand for Ozempic (semaglutide for diabetes) and Wegovy (semaglutide for weight management) increased substantially from 2022 following publication of STEP trial weight-loss data and associated media coverage. Novo Nordisk's global manufacturing capacity was insufficient to meet this accelerated demand, resulting in MHRA-notified supply disruptions across 2022–2024. Novo Nordisk subsequently invested in significant manufacturing capacity expansion, and supply constraints have progressively improved.

Liraglutide is a synthetic analogue of the gut hormone GLP-1, modified with a C-16 fatty acid chain to extend its plasma half-life to approximately 13 hours for once-daily dosing. In the UK it is licensed as Victoza for type 2 diabetes management and as Saxenda for chronic weight management. It was the first GLP-1 receptor agonist approved for obesity pharmacotherapy, establishing the mechanistic proof-of-concept for this entire therapeutic class.

Semaglutide 2.4 mg weekly (STEP 1: −14.9%) produces approximately twice the weight loss of liraglutide 3.0 mg daily (SCALE: −8.0%) in comparable non-diabetic obese populations. This difference is attributable to semaglutide's greater central appetite-suppressing potency, its longer half-life producing more stable receptor occupation, and its higher dose relative to the GLP-1 receptor agonism benchmark. Daily injection versus once-weekly administration is also a practical differentiator in clinical and research contexts.

Victoza (liraglutide for type 2 diabetes) is available on NHS prescription within approved prescribing guidelines. Saxenda (liraglutide for weight management) has had restricted NHS availability, with access through specialist obesity services and subject to local formulary decisions. NICE guidance TA664 covers liraglutide for weight management with specific BMI and comorbidity criteria. Private prescribing is available through appropriate clinicians.

The difference stems from their fatty acid conjugation strategies: liraglutide uses a C-16 palmitic acid chain, producing albumin binding that extends half-life to approximately 13 hours—sufficient for once-daily dosing. Semaglutide uses a C-18 fatty diacid chain with a longer hydrophilic spacer, producing tighter albumin binding and a half-life of approximately 7 days. Novo Nordisk specifically engineered semaglutide's linker chemistry to achieve this further extension after liraglutide established the feasibility of the approach.

The LEADER trial enrolled 9,340 adults with type 2 diabetes and high cardiovascular risk, followed for a median 3.8 years. Liraglutide 1.8 mg daily reduced the primary MACE composite (cardiovascular death, non-fatal MI, non-fatal stroke) by 13% relative to placebo (HR 0.87), driven principally by a significant 22% reduction in cardiovascular death. This was the first positive cardiovascular outcomes trial for any GLP-1 receptor agonist and established the cardiovascular protective framework that subsequent SELECT and SUSTAIN-6 trials built upon.

Yes. While semaglutide and tirzepatide have largely superseded liraglutide in new clinical prescribing for weight management due to greater efficacy and more convenient weekly dosing, liraglutide retains clinical relevance for patients with specific tolerability profiles, in type 2 diabetes management, and as a comparator in ongoing mechanistic research. Its comprehensive clinical dataset—SCALE, LEADER, LEAD 1–6—remains a foundational reference for incretin biology researchers.

AOD-9604 is a synthetic peptide corresponding to residues 177–191 of human growth hormone, with an additional N-terminal tyrosine residue. It was engineered to isolate the lipolytic (fat-mobilising) activity of hGH from its growth-promoting and diabetogenic effects. Intact hGH stimulates IGF-1 production and promotes linear growth via its N-terminal domain; AOD-9604 lacks these structural elements and does not activate the IGF-1 axis at research doses.

No. Despite advancing to Phase 2b/3 clinical evaluation, the AOD-9604 clinical programme did not demonstrate sufficient efficacy at the primary weight-loss endpoint required for marketing authorisation approval. However, it did receive a US FDA GRAS (Generally Recognised As Safe) notification as a food ingredient, reflecting the extensive clinical safety characterisation. The failure to achieve regulatory approval was principally an efficacy issue rather than a safety one.

Preclinical studies and Phase 2 clinical data consistently show no measurable elevation of circulating IGF-1 at therapeutic doses of AOD-9604. This IGF-1 axis independence is the defining pharmacological distinction from intact hGH, and was a central feature of the development rationale. The absence of IGF-1 stimulation means AOD-9604 avoids the insulin resistance, glucose intolerance, and acromegalic adverse effects associated with exogenous hGH administration.

AOD-9604 is not approved by the MHRA for any therapeutic indication and is not a licensed medicine in the UK. It may be procured as a research peptide for legitimate preclinical or in vitro scientific investigation through specialist research chemical suppliers, subject to appropriate institutional governance and ethics approval. Its supply or use for human therapeutic purposes outside of authorised clinical trials is not permitted under UK medicines regulations.

AOD-9604 and HGH Fragment 176-191 are closely related but structurally distinct. HGH Fragment 176-191 corresponds to residues 176–191 of the hGH sequence (16 amino acids). AOD-9604 corresponds to residues 177–191 with an additional N-terminal tyrosine, giving it a different N-terminal residue and potentially different receptor interaction profile. AOD-9604 was the subject of Metabolic Pharmaceuticals' formal clinical development programme; HGH Fragment 176-191 is primarily a preclinical research tool.

Phase 1 trials confirmed AOD-9604's safety and pharmacokinetic profile. Phase 2 dose-ranging studies demonstrated a favourable safety profile including no IGF-1 elevation, no adverse glucose effects, and no hGH-related adverse events across all doses investigated. Efficacy signals for weight loss were observed in some Phase 2 substudies but were insufficient in magnitude and consistency to meet Phase 3 primary endpoint requirements, leading to the programme's discontinuation as an obesity drug.

HGH Fragment 176-191 is a synthetic 16-amino acid peptide corresponding to the C-terminal lipolytic domain of human growth hormone. In preclinical adipocyte studies and rodent models, it stimulates lipolysis (triglyceride breakdown) and inhibits lipogenesis (new fat synthesis) without activating the IGF-1 axis or producing the growth-promoting, diabetogenic effects of intact hGH. It is used primarily as a mechanistic research tool in adipose tissue biology.

HGH Fragment 176-191 comprises residues 176–191 of the mature hGH sequence (16 amino acids). AOD-9604 is the same C-terminal fragment but with an additional N-terminal tyrosine residue (residues 177–191 plus tyrosine), developed by Metabolic Pharmaceuticals for formal drug development. AOD-9604 underwent Phase 2 and Phase 3 clinical trials and received a US FDA GRAS notification; HGH Fragment 176-191 has remained a preclinical research tool without comparable clinical development.

Preclinical data consistently show no measurable elevation of circulating IGF-1 at doses producing significant lipolytic effects. This IGF-1 axis independence is the key pharmacological distinction from intact hGH and is attributable to the fragment lacking the N-terminal structural elements required for growth hormone receptor dimer activation and downstream JAK2/STAT5/IGF-1 gene transcription.

No. HGH Fragment 176-191 is not approved by the MHRA for any therapeutic indication and is not a licensed medicine. It is a research compound available for preclinical or in vitro investigation through specialist research chemical suppliers under appropriate institutional governance. It has not undergone formal Phase 2/3 clinical evaluation equivalent to its AOD-9604 derivative.

The internal disulphide bond between cysteine residues at positions 182 and 189 of the fragment creates a constrained cyclic loop conformation that is essential for biological activity. Studies using reduced (linearised) forms show complete loss of lipolytic effect, establishing that the cyclic structure—not the linear sequence alone—constitutes the active pharmacophore. This has practical implications for storage and reconstitution: the peptide must not be exposed to reducing agents that would cleave the disulphide bond.

The compound has been characterised in isolated rat adipocyte lipolysis assays, 3T3-L1 differentiated adipocyte cell culture, diet-induced obese rat models, genetically obese ob/ob mice, and Zucker fatty rat models. These diverse model systems have consistently demonstrated the fragment's lipolytic activity and IGF-1 axis independence, providing a reasonably robust preclinical evidence base for the mechanistic claims, though human pharmacology data are essentially absent.

Tesamorelin is a synthetic GHRH analogue that stimulates the pituitary to produce its own growth hormone in pulsatile fashion, rather than directly administering exogenous GH. This distinction is important: endogenous pulsatile GH release preserves normal somatostatin-mediated feedback regulation, maintaining IGF-1 within physiological ranges and avoiding the runaway GH excess, insulin resistance, and acromegalic effects associated with supraphysiological exogenous GH administration.

Tesamorelin (Egrifta) is approved by the US FDA for the treatment of excess visceral abdominal fat in HIV-infected adults with lipodystrophy. This is its sole approved indication globally. It is not approved by the MHRA (UK), the EMA (EU), or any other regulatory authority outside the United States for any indication. In the UK it is classified as a research compound.

Yes. Research programmes have investigated tesamorelin in: metabolic syndrome and abdominal obesity in HIV-negative individuals; mild cognitive impairment and early Alzheimer's disease (TRIUMPHANT-AD programme), based on GH/IGF-1's roles in hippocampal neuroplasticity; non-alcoholic fatty liver disease, given GH's known effects on hepatic lipid metabolism; and age-related GH deficiency. These studies leverage the established safety database from the HIV lipodystrophy programme.

Yes. GH axis stimulation by tesamorelin can impair insulin sensitivity through classic GH counter-regulatory effects on glucose uptake. In LIPO trial populations, a small proportion of participants developed glucose intolerance requiring monitoring and in some cases discontinuation. Fasting glucose and HbA1c monitoring are standard in clinical research protocols using tesamorelin. The magnitude of glucose impairment is generally less than seen with exogenous GH administration, consistent with the lower and more physiologically regulated IGF-1 elevations produced.

Tesamorelin is not approved by the MHRA for any indication in the UK. It is a research compound that may be procured for preclinical or in vitro investigation under appropriate institutional governance, or studied in humans only within a formally authorised clinical trial with a Clinical Trial Authorisation (CTA). Supply for unlicensed human therapeutic use is not permitted under the Human Medicines Regulations 2012. GHRH-class peptides are prohibited by WADA.

Tesamorelin is administered via once-daily subcutaneous injection, typically into the abdominal region. Its plasma half-life is approximately 26–38 minutes — much shorter than semaglutide or tirzepatide — reflecting its mechanism of action as a pulsatile stimulus rather than a sustained receptor occupant. The pharmacodynamic effects on GH pulsatility persist well beyond this short plasma half-life through downstream pituitary signalling, and daily dosing is sufficient to maintain significant VAT reduction in clinical research.

CJC-1295 is a GHRH receptor agonist that stimulates pituitary GH secretion through the Gsα/cAMP pathway; Ipamorelin is a ghrelin receptor (GHS-R1a) agonist that stimulates GH secretion through a separate Gq/IP3/calcium pathway. Because these two pathways converge synergistically on GH vesicle exocytosis, co-administration produces GH release substantially greater than either compound achieves alone. This synergistic GH secretagogue profile is the scientific rationale for studying the two compounds as a research combination.

CJC-1295 with DAC (Drug Affinity Complex) contains a reactive maleimide group that spontaneously forms a covalent bond with Cys34 of serum albumin in vivo, producing a half-life of approximately 7–8 days—sufficient for once-weekly injection. CJC-1295 without DAC (Mod GRF(1-29)) lacks this albumin-binding moiety and has a half-life of approximately 30 minutes, producing transient GH pulses that more closely mimic endogenous GHRH pulsatility. The two forms produce different pharmacodynamic profiles and are used for different research objectives.

No. While all three are GHS-R1a agonists (ghrelin mimetics), ipamorelin is distinguished by its high selectivity: it produces GH secretion with minimal co-stimulation of ACTH, cortisol, or prolactin. GHRP-6 and GHRP-2 activate GHS-R1a but also stimulate corticotroph and lactotroph secretion at GH-effective doses, introducing confounding non-GH pituitary effects in research. This selectivity makes ipamorelin the preferred GHS-R1a agonist for research specifically investigating GH secretagogue biology.

No. Neither CJC-1295 nor Ipamorelin is approved by the MHRA for any therapeutic indication in the UK. Both are research compounds. CJC-1295 was studied in Phase 1/2 clinical trials by ConjuChem but was not advanced to regulatory submission. Ipamorelin was studied by Novo Nordisk and Helsinn for postoperative ileus but not approved. Their supply for human use outside of authorised clinical trials is not permitted under the Human Medicines Regulations 2012.

Both compounds increase circulating IGF-1 through stimulation of pituitary GH secretion, which then acts on hepatic GH receptors to drive IGF-1 synthesis. CJC-1295 with DAC Phase 1 data documented mean IGF-1 increases of 1.5–3-fold above baseline lasting up to 28 days following a single injection. The magnitude of IGF-1 elevation is dose-dependent and, at research doses, is expected to remain within the physiological range rather than producing the supraphysiological elevations associated with exogenous GH abuse.

The principal safety concerns are those associated with GH axis activation: glucose intolerance from GH's counter-regulatory effects on insulin sensitivity; water retention and peripheral oedema; carpal tunnel syndrome symptoms at sustained higher GH elevations; and theoretical malignancy promotion risk from sustained IGF-1 elevation. CJC-1295 Phase 2 data also noted the development of anti-peptide antibodies in some participants. Neither compound has published human safety data beyond 28-day treatment periods.

WADA prohibits all GH-releasing peptides and growth hormone secretagogues, including CJC-1295, Ipamorelin, and the entire GHS-R1a agonist class. The prohibition is based on the anabolic and lipolytic effects of increased GH and IGF-1 secretion, which confer potential performance-enhancing advantages in strength, power, and recovery. Detection methods for GH secretagogue use—including urinary and blood assays targeting metabolites and downstream biomarkers—have been developed and are used in doping control programmes.

An investigational long-acting amylin analogue developed by Novo Nordisk, studied principally in combination with semaglutide (CagriSema) for chronic weight management. Not licensed for human therapeutic use in the UK.

No. Cagrilintide is investigational and is not licensed by the MHRA for any human therapeutic indication. Use outside an authorised clinical trial is not lawful.

Cagrilintide acts on amylin pathways; GLP-1 receptor agonists act on the GLP-1 receptor. The combined CagriSema therapy hypothesises additive weight-management benefit from engaging both mechanisms.

An investigational fixed combination of cagrilintide (amylin analogue) and semaglutide (GLP-1 receptor agonist), in active phase 3 evaluation for obesity and type 2 diabetes.

No. CagriSema is investigational and is not licensed by the MHRA for any human therapeutic indication.

CagriSema adds amylin signalling via cagrilintide to the GLP-1 receptor agonism of semaglutide. The combined mechanism is hypothesised to produce greater body-weight reduction than semaglutide alone, with confirmation depending on the phase 3 readouts.

Dulaglutide (Trulicity) is a once-weekly GLP-1 receptor agonist licensed in the UK for type 2 diabetes. It is the active comparator in SURPASS-CVOT.

Dulaglutide is a GLP-1 mono-agonist. Tirzepatide is a dual GLP-1/GIP agonist; semaglutide is a GLP-1 mono-agonist available at a higher anti-obesity dose. Cross-trial comparison should be done with care; SURPASS-CVOT is the head-to-head trial of tirzepatide versus dulaglutide.

No. Dulaglutide is licensed for type 2 diabetes glycaemic control. Anti-obesity indications in the GLP-1 class are held by other agents (Wegovy, Saxenda, Mounjaro at the higher-dose obesity arm).

An investigational long-acting GLP-1 / glucagon dual receptor agonist co-developed by Boehringer Ingelheim and Zealand Pharma. Phase 3 programmes for obesity and MASH are in active enrolment / readout.

No. Survodutide is investigational and is not licensed by the MHRA for any human therapeutic indication.

Tirzepatide is a GLP-1 / GIP dual agonist; survodutide is a GLP-1 / glucagon dual agonist. The added glucagon-receptor component is hypothesised to drive energy expenditure and hepatic fat oxidation. Head-to-head trials have not been published at the time of review.

An investigational GLP-1 / glucagon dual receptor agonist developed by Altimmune. Phase 2 programmes for obesity and MASH have read out; phase 3 development is the next step.

No. Pemvidutide is investigational worldwide at the time of review.

An investigational GLP-1 / glucagon dual receptor agonist developed by Innovent Biologics in China under licence from Eli Lilly. Phase 3 programmes in obesity and T2D are anchored in the Chinese regulatory pathway.

No. Mazdutide is investigational outside its regional approval pathway and is not licensed for human therapeutic use in the UK.

Cotadutide's development programme has had material changes during 2023-2025. Obesity development has been discontinued; narrower indications have been retained. The current ClinicalTrials.gov / AstraZeneca pipeline is the authoritative reference.

No. Cotadutide is investigational and is not licensed for any human therapeutic use in the UK.

No. Orforglipron is a small-molecule non-peptide GLP-1 receptor agonist. It is listed here for cross-class context with the peptide GLP-1 RAs that dominate the existing licensed landscape.

No. Orforglipron is investigational across all major jurisdictions at the time of review.

Rybelsus is peptide semaglutide co-formulated with the SNAC absorption enhancer; absorption requires a fasted state. Orforglipron is a small-molecule agonist absorbable orally without an enhancer.

Danuglipron's development programme has had material changes during 2023-2025, including discontinuation of the twice-daily formulation in late 2023. Subsequent programme changes have followed. The current ClinicalTrials.gov / Pfizer pipeline is the authoritative reference.

No. Danuglipron is investigational and is not licensed by the MHRA for any human therapeutic indication.

Pramlintide (Symlin) is a synthetic analogue of the pancreatic hormone amylin, approved by the FDA in the United States as an adjunct to mealtime insulin in type 1 and type 2 diabetes. It slows gastric emptying, suppresses postprandial glucagon and signals satiety via the area postrema.

No. Pramlintide is not currently licensed by the MHRA for any human therapeutic indication. It holds FDA approval in the US as Symlin, but it does not hold a UK marketing authorisation. UK access would require appropriate specialist and regulatory engagement.

Pramlintide is the first-generation amylin analogue and established the pharmacological proof-of-concept for amylin-receptor agonism in diabetes and weight management. Cagrilintide (AM833, Novo Nordisk) is a next-generation amylin analogue engineered with fatty-acid acylation for once-weekly albumin-bound dosing, overcoming pramlintide's short half-life that requires 2–3 daily injections.

Pramlintide has a half-life of approximately 48 minutes. It must be injected subcutaneously immediately before each main meal to match the postprandial window during which amylin effects (slowing gastric emptying, suppressing glucagon) are pharmacologically relevant.

Exenatide is a GLP-1 receptor agonist derived from exendin-4, a peptide found in Gila monster venom. It was the first GLP-1 receptor agonist approved in clinical practice (FDA 2005). Available as Byetta (twice-daily) and Bydureon BCise (once-weekly extended-release).

Exenatide products have historically held MHRA marketing authorisations for type 2 diabetes. As a UK prescription-only medicine, access requires a qualified prescriber. By 2026, newer GLP-1 agents (semaglutide, tirzepatide, dulaglutide) dominate UK NHS prescribing. Clinicians should confirm current product availability via the MHRA register.

EXSCEL (Exenatide Study of Cardiovascular Event Lowering) was a cardiovascular outcomes trial published in the NEJM in 2017. It evaluated once-weekly exenatide versus placebo in adults with type 2 diabetes across a broad CV risk spectrum. Exenatide demonstrated non-inferiority on MACE-3 but did not achieve statistical superiority on the primary cardiovascular endpoint.

Exenatide (exendin-4 derived) was the pioneering molecule that established clinical proof-of-concept for GLP-1 receptor agonism. Later agents — liraglutide, dulaglutide, semaglutide — are engineered as GLP-1 analogues with structural modifications for extended half-life and improved tolerability. Semaglutide and tirzepatide have demonstrated greater HbA1c and body-weight reductions in head-to-head and cross-trial data.

An investigational once-weekly GLP-1 receptor agonist based on an exendin-4 peptide fused to an IgG4 Fc domain (Fc-fusion). Developed by Hanmi Pharmaceutical and later partnered with Sanofi. The AMPLITUDE-O trial (NEJM 2021) reported a statistically significant reduction in MACE-3 in adults with T2D and high CV risk or CKD.

Efpeglenatide is investigational and is not licensed by the MHRA for any human therapeutic indication. Despite the cardiovascular outcome data from AMPLITUDE-O, the programme has experienced ownership and prioritisation changes during 2021–2026, and no MHRA marketing authorisation has followed at the time of review. Efpeglenatide must not be used outside an appropriately authorised research setting.

AMPLITUDE-O (NEJM 2021, Gerstein HC et al.) was a cardiovascular outcomes trial in 4,076 adults with T2D and high CV risk or CKD. It reported that efpeglenatide reduced the primary composite endpoint of MACE-3 (CV death, non-fatal MI, non-fatal stroke) with a hazard ratio of approximately 0.73 (95% CI approximately 0.58–0.92). Renal composite outcomes also favoured efpeglenatide.

Like dulaglutide and once-weekly semaglutide, efpeglenatide is designed for weekly subcutaneous injection. Its distinctive structural feature is the exendin-4 peptide fused to an IgG4 Fc domain (Fc-fusion), compared with the GLP-1 analogue + IgG4 Fc approach of dulaglutide or the fatty-acid-acylated GLP-1 analogue approach of semaglutide. The programme status has evolved since AMPLITUDE-O.

An investigational peptide-antibody conjugate developed by Amgen. The antibody backbone delivers GIP receptor antagonism while the conjugated peptide delivers GLP-1 receptor agonism. Designed for monthly subcutaneous administration.

Tirzepatide is a GLP-1 / GIP dual agonist — it activates both receptors. MariTide antagonises the GIP receptor while agonising the GLP-1 receptor. The two molecules approach the GIP receptor from opposite directions, and head-to-head trial data would be required to characterise the comparative clinical effect.

No. MariTide is investigational worldwide at the time of review.

Metabolic peptides are short chains of amino acids (typically 10-50 residues) that act on metabolic-pathway receptors — most commonly the GLP-1, GIP, glucagon, GHRH and ghrelin receptors. They differ from small-molecule drugs in size (peptides are ~10-50× larger), in administration (most require subcutaneous injection because they would be digested if taken orally; Rybelsus is the unusual oral exception), and in mechanism (they bind their target receptor with high specificity, whereas small molecules can have broader off-target effects). The clinical advantage of peptide pharmacology is precision; the trade-off is the injection route and a higher cost of manufacture.

As of mid-2026 the published trial data places the compounds in this order, from largest to smallest mean weight reduction: retatrutide (~24% at 48 weeks in Phase 2, 12 mg dose, NEJM 2023), tirzepatide (~22% at 72 weeks in SURMOUNT-1, 15 mg weekly), semaglutide (~15% at 68 weeks in STEP-1, 2.4 mg weekly), liraglutide (~8% at 56 weeks in SCALE, 3 mg daily). Retatrutide has only Phase 2 data; tirzepatide and semaglutide have complete Phase 3 evidence packages including cardiovascular outcomes.

Three metabolic peptides are MHRA-licensed prescription medicines in the UK: tirzepatide (Mounjaro), semaglutide (Ozempic, Wegovy, Rybelsus) and liraglutide (Saxenda, Victoza). All other compounds — retatrutide, AOD-9604, HGH Fragment 176-191, tesamorelin, CJC-1295, ipamorelin — are not licensed for human therapeutic use in the UK. Research-grade material of these is supplied for laboratory and analytical use only and must not be administered to humans. The MHRA's Yellow Card Scheme handles pharmacovigilance for the licensed medicines.

In authorised laboratory research contexts, lyophilised peptides are typically stored at -20 °C until reconstitution; once reconstituted with bacteriostatic water (0.9% benzyl alcohol) most retain potency at 2-8 °C for several weeks depending on the compound. This is institutional research-handling information for governance reference only. This site does not publish reconstitution maths, dose calculators or self-administration instructions, and does not recommend any product or supplier. See our laboratory procurement governance page for the institutional research context.

GLP-1 monoagonists (semaglutide, liraglutide) bind only the GLP-1 receptor. Dual GIP/GLP-1 agonists (tirzepatide) bind both GLP-1 and GIP receptors, exploiting the synergy between two distinct incretin pathways for greater weight and glycaemic effects. Triple agonists (retatrutide) add a third — glucagon-receptor agonism — which increases energy expenditure and accelerates hepatic fatty-acid oxidation on top of incretin-driven appetite suppression. Each successive class has produced larger trial-measured weight reductions; the trade-off is that newer compounds have shorter safety records.

Because the legal and safety status of these two categories is completely different. An MHRA-licensed prescription medicine (Mounjaro, Wegovy, Ozempic, Saxenda, Rybelsus, Victoza) has passed regulatory scrutiny on manufacturing, purity, labelling and clinical evidence, and is supplied to humans by licensed UK prescribers. A research peptide is not approved for human therapeutic use and may not be manufactured to pharmaceutical-grade standards. Conflating the two — for example by sourcing a 'compounded' or 'research-grade' product for personal use — exposes the user to unknown purity, dosing, and adverse-event risk. We do not endorse human use outside the MHRA-licensed pathway.

MHRA-licensed prescription medicines (Mounjaro, Wegovy, Ozempic, Saxenda, Rybelsus, Victoza, Trulicity) are legally supplied only via a prescription from a UK-registered prescriber, dispensed by a registered pharmacy following appropriate clinical assessment. Unlicensed research-only peptides are not licensed by the MHRA for human therapeutic use; administration to humans outside an appropriately authorised research setting is not lawful. This site does not list, rank or recommend suppliers and does not provide guidance on obtaining peptides. See our UK regulatory status hub for the legal context and the laboratory procurement governance page for institutional research-only framing.

Mixed. Liraglutide has the longest exposure record (approved 2010) and the LEADER cardiovascular outcomes trial demonstrated long-term safety in type 2 diabetes. Semaglutide has SELECT (cardiovascular outcomes in non-diabetic obesity, 2023) and SUSTAIN-6. Tirzepatide's long-term data is still maturing — SURMOUNT-MMO is the in-progress CV outcomes trial. Retatrutide is too new for any long-term data; its Phase 3 TRIUMPH programme first read-outs are expected from 2025-2027. Research peptides outside this group (AOD-9604, HGH 176-191, CJC-1295) have no long-term human safety data and remain confined to laboratory research.

The SELECT trial (semaglutide 2.4 mg in adults with overweight or obesity and established cardiovascular disease) showed a 20% reduction in major adverse cardiovascular events (MACE) over 39.8 months. The effect appears larger than weight loss alone would predict, suggesting direct cardiovascular mechanisms — possibly endothelial function, anti-inflammatory effects on atherosclerotic plaque, or effects on cardiac contractility. SUSTAIN-6 showed similar MACE reduction in type 2 diabetes. Tirzepatide's SURMOUNT-MMO and SURPASS-CVOT are testing whether the dual-agonist class delivers a comparable CV signal; interim data is consistent but final read-out is expected 2026-2027.

Trial data shows substantial weight regain after discontinuation. The STEP-4 trial randomised participants who had achieved weight loss on semaglutide 2.4 mg to either continue or switch to placebo; the placebo group regained approximately two-thirds of the lost weight within 48 weeks. SURMOUNT-4 showed a similar pattern with tirzepatide. The implication is that these compounds work through ongoing receptor agonism rather than producing durable changes in appetite biology — comparable in this respect to most chronic-disease pharmacotherapy. Long-term human use is therefore the licensed prescribing model.

The dominant interaction is mechanism-related: delayed gastric emptying can slow absorption of orally administered medicines taken at the same time, particularly narrow-therapeutic-index drugs like warfarin or levothyroxine. The BNF lists relevant interactions for the MHRA-licensed brands. Co-administration with insulin or sulphonylureas substantially increases hypoglycaemia risk — these combinations require dose reduction of the insulin/SU. No clinically meaningful CYP450-mediated interactions have been reported for the peptide class. For research peptides this question does not arise because the compounds are not for human use.

Both are tirzepatide, manufactured by Eli Lilly, with identical molecular composition and pharmacology. Mounjaro is the brand name used in the UK and EU (originally approved for type 2 diabetes, weight management indication added 2024). Zepbound is the US-market brand name for the weight-management indication. The product, dose schedule and clinical evidence are the same; the brand differentiation is purely commercial.