Editorial note: this article summarises published research on GLP-1 receptor agonists and related multi-receptor peptides. Baclabs does not sell semaglutide, tirzepatide, retatrutide, cagrilintide or any peptide; we supply bacteriostatic water and reconstitution consumables. Nothing here is medical advice.
GLP-1 peptides are the injectable medicines that have reshaped obesity and type 2 diabetes treatment over the past decade. Liraglutide, semaglutide and tirzepatide are licensed in the UK; retatrutide and CagriSema (cagrilintide plus semaglutide) are investigational. All borrow from the same biology: the gut hormones released after a meal that tell the pancreas to secrete insulin and the brain to stop eating.
This guide covers the shared mechanism, what separates a single agonist from a dual or triple agonist, the headline trial results, the licensed dosing from the UK Summaries of Product Characteristics (SmPCs), the adverse-effect profile, the UK regulatory position, and the reconstitution arithmetic that applies to lyophilised vials rather than pens.
Supporting articles: tirzepatide vs semaglutide, retatrutide, cagrilintide and CagriSema, and reconstitution protocols for lyophilised GLP-1 vials.
How GLP-1 peptides work
Glucagon-like peptide-1 (GLP-1) is a 30-amino-acid hormone released by intestinal L-cells when nutrients arrive. It binds the GLP-1 receptor on pancreatic beta cells and increases insulin secretion in a glucose-dependent way, so it does little when glucose is already normal, which is why GLP-1 monotherapy rarely causes hypoglycaemia. The same receptor in the hypothalamus and brainstem reduces appetite and food reward, and in the stomach slows gastric emptying. People eat less and feel full sooner.
Native GLP-1 survives only minutes before the enzyme dipeptidyl peptidase-4 (DPP-4) cleaves it. Every GLP-1 medicine is an engineered analogue built to resist that cleavage. Liraglutide carries a fatty acid chain that binds albumin, giving a half-life of roughly 13 hours and once-daily dosing; semaglutide uses a longer fatty diacid and an amino acid substitution at the cleavage site, giving a half-life of about a week.
From single to multi-receptor agonists
The second incretin, glucose-dependent insulinotropic polypeptide (GIP), was long dismissed as a target because its insulin effect is blunted in type 2 diabetes. Tirzepatide, a single 39-amino-acid peptide activating both GIP and GLP-1 receptors, changed that view. Willard and colleagues called it “imbalanced and biased”: it binds the GIP receptor as tightly as native GIP but the GLP-1 receptor about five-fold more weakly, and at the GLP-1 receptor favours cyclic AMP signalling over beta-arrestin recruitment [1]. The result is more weight loss than a GLP-1 agonist alone without proportionally more gastrointestinal effect.
Retatrutide adds a third target, the glucagon receptor. Glucagon raises energy expenditure and hepatic fat oxidation and would normally raise blood glucose, but paired with GLP-1 and GIP activity the net effect in trials has been more weight loss and better glycaemia [2]. CagriSema pairs semaglutide with cagrilintide, a long-acting analogue of amylin, a hormone co-secreted with insulin that acts on the area postrema in the hindbrain to reduce food intake and slow gastric emptying, complementing rather than duplicating GLP-1 [3].
Clinical profiles of each compound
Liraglutide (Saxenda, Victoza)
Liraglutide was the first GLP-1 analogue licensed for weight management. In the SCALE Obesity and Prediabetes trial, 3,731 adults without diabetes received liraglutide 3.0 mg daily or placebo with lifestyle intervention. At 56 weeks, mean weight loss was 8.0% versus 2.6%; 63.2% of the liraglutide group lost at least 5% of body weight against 27.1% on placebo [4]. Nausea affected 40.2% of liraglutide recipients.
Semaglutide (Wegovy, Ozempic)
STEP 1 randomised 1,961 adults without diabetes to semaglutide 2.4 mg weekly or placebo and found a mean weight change of −14.9% versus −2.4% at 68 weeks [5]. The SELECT trial then followed 17,604 people with cardiovascular disease and overweight or obesity, but no diabetes, for a mean of 39.8 months: semaglutide reduced major adverse cardiovascular events by 20% (hazard ratio 0.80), from 8.0% to 6.5% [6]. That result added a cardiovascular indication to the Wegovy licence.
Tirzepatide (Mounjaro)
SURMOUNT-1 randomised 2,539 adults with obesity to tirzepatide 5, 10 or 15 mg weekly or placebo for 72 weeks. Mean weight loss was 16.0%, 21.4% and 22.5% respectively, against 2.4% with placebo; 63% of the 15 mg group lost at least 20% of body weight [7]. The head-to-head SURMOUNT-5 trial, published in 2025, then compared tirzepatide with semaglutide directly in 751 adults: at 72 weeks, weight fell 20.2% with tirzepatide and 13.7% with semaglutide, and waist circumference fell 18.4 cm versus 13.0 cm [8]. The tirzepatide vs semaglutide article examines that comparison in detail.
Retatrutide (investigational)
Retatrutide’s phase 2 trial in 338 adults with obesity reported weight loss of 24.2% at 48 weeks in the 12 mg group, versus 2.1% with placebo [2]. Lilly’s phase 3 TRIUMPH programme reported topline results through 2025 and 2026: TRIUMPH-1 (2,339 participants) showed mean weight loss of 19.0%, 25.9% and 28.3% at 80 weeks for 4, 9 and 12 mg respectively, and TRIUMPH-2 and TRIUMPH-3 in people with type 2 diabetes and with cardiovascular disease reported 20.8% and 22.6% at the 12 mg dose [9][10]. Lilly has said it plans to submit to the US Food and Drug Administration (FDA) in the first quarter of 2027. As of September 2026, retatrutide is not licensed anywhere. See the retatrutide science article.
Cagrilintide and CagriSema (investigational)
In a 2021 phase 2 dose-finding trial, once-weekly cagrilintide 4.5 mg alone produced 10.8% weight loss at 26 weeks, beating liraglutide 3.0 mg daily at 9.0% [3]. Combined with semaglutide as CagriSema in the phase 3 REDEFINE 1 trial (3,417 participants, 68 weeks), the treatment-policy estimand gave −20.4% for CagriSema, −14.9% for semaglutide alone, −11.5% for cagrilintide alone and −3.0% for placebo [11]. REDEFINE 2, in people with type 2 diabetes, reported −13.7% versus −3.4% [11]. The cagrilintide and CagriSema article covers the amylin mechanism.
| Compound | Receptors | Dosing | Key trial | Mean weight change (active vs placebo) | UK status |
|---|---|---|---|---|---|
| Liraglutide | GLP-1 | Daily | SCALE, 56 weeks [4] | −8.0% vs −2.6% | Licensed (Saxenda) |
| Semaglutide | GLP-1 | Weekly | STEP 1, 68 weeks [5] | −14.9% vs −2.4% | Licensed (Wegovy, Ozempic) |
| Tirzepatide | GIP + GLP-1 | Weekly | SURMOUNT-1, 72 weeks [7] | −22.5% (15 mg) vs −2.4% | Licensed (Mounjaro) |
| CagriSema | Amylin + GLP-1 | Weekly | REDEFINE 1, 68 weeks [11] | −20.4% vs −3.0% | Investigational |
| Retatrutide | GIP + GLP-1 + glucagon | Weekly | TRIUMPH-1, 80 weeks [9] | −28.3% (12 mg) vs −2.2% | Investigational |
Cross-trial comparisons are indicative only; populations, durations and estimands differ, which is why the direct SURMOUNT-5 comparison carries more weight.
Licensed dosing in the UK
All three licensed products are pre-filled pens and prescription-only medicines under the Human Medicines Regulations 2012. The dosing below is from the current SmPCs on medicines.org.uk, reproduced for reference.
| Product | Starting dose | Escalation | Maintenance |
|---|---|---|---|
| Wegovy (semaglutide) [12] | 0.25 mg weekly, weeks 1–4 | 0.5 mg (weeks 5–8), 1 mg (weeks 9–12), 1.7 mg (weeks 13–16) | 2.4 mg weekly; the current SmPC also lists an optional 7.2 mg dose for obesity |
| Ozempic (semaglutide) [13] | 0.25 mg weekly for 4 weeks | 0.5 mg, then 1 mg after at least 4 weeks each | Up to 2 mg weekly (type 2 diabetes) |
| Mounjaro (tirzepatide) [14] | 2.5 mg weekly for 4 weeks | Increase by 2.5 mg no more often than every 4 weeks | 5, 10 or 15 mg weekly |
| Saxenda (liraglutide) [15] | 0.6 mg daily | Increase by 0.6 mg each week over 4 weeks | 3.0 mg daily; stop if under 5% weight loss after 12 weeks at 3.0 mg |
The slow escalation is deliberate: gastrointestinal effects cluster in the titration phase, and every SmPC allows a step to be delayed if it is not tolerated.
NICE and NHS access
NICE technology appraisal TA1026 recommends tirzepatide for adults with a body mass index (BMI) of at least 35 kg/m² and at least one weight-related comorbidity, with lower thresholds for some ethnic groups; NHS England is phasing it into primary care from June 2025, starting with BMI 40 or more and at least four comorbidities [16]. Wegovy is available through specialist weight management services under TA875. Private prescribers can supply either to eligible patients.
Adverse effects and safety signals
The dominant adverse effects are gastrointestinal. The Wegovy SmPC lists nausea at 43.9%, diarrhoea 29.7%, vomiting 24.5% and constipation 24.2% [12]; in SURMOUNT-1, nausea affected 24.6–33.3% of tirzepatide recipients versus 9.5% on placebo [7]; in TRIUMPH-1, nausea reached 28.6–42.4% and discontinuation for adverse events 11.3% at 12 mg [9]. Beyond the gut, four signals recur:
- Acute pancreatitis. In January 2026 the Medicines and Healthcare products Regulatory Agency (MHRA) issued a Drug Safety Update strengthening warnings for all GLP-1 and dual GIP/GLP-1 agonists after rare necrotising and fatal cases. Treatment is to be stopped if pancreatitis is suspected and not restarted if confirmed [17].
- Gallbladder disease. Cholelithiasis occurred in 1.6% of Wegovy-treated patients in trials [12]; higher rates of cholelithiasis and cholecystitis versus placebo are also noted for liraglutide [15].
- Diabetic retinopathy. People with type 2 diabetes and existing retinopathy showed an increased risk of complications with semaglutide, and the Ozempic SmPC does not recommend the 2 mg dose where retinopathy is uncontrolled [13].
- Thyroid C-cell tumours. In rodents, semaglutide causes thyroid C-cell tumours at clinically relevant exposures. The US label carries a boxed warning and contraindicates use in people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 [18]. Human relevance has not been established, and the UK SmPCs do not carry an equivalent contraindication, though the Saxenda SmPC advises caution in pre-existing thyroid disease [15].
Retatrutide adds two effects the GLP-1 agonists do not show to the same degree: a dose-dependent rise in heart rate over the first 24 weeks of phase 2 [2], and dysesthesia (abnormal skin sensation) in up to 20.9% of participants at 12 mg in TRIUMPH-4 [19].
The UK regulatory picture
Semaglutide, tirzepatide and liraglutide are prescription-only medicines. Retatrutide and CagriSema hold no marketing authorisation in the UK, the EU or the US, so any vial advertised under those names is supplied outside the licensed system. The MHRA treats that market as an enforcement priority: in October 2025 it shut down an East Midlands facility producing counterfeit tirzepatide and unlicensed retatrutide pens [20], and in May 2026 it seized roughly 12,000 doses of unlicensed weight-loss medicines including retatrutide [21]. Unlicensed injectables have no assured identity, sterility or potency.
Reconstitution: why the diluent matters
Licensed GLP-1 products arrive as solutions in pre-filled pens and need no mixing. Lyophilised (freeze-dried) research vials are a powder of stated mass, typically 5–15 mg for tirzepatide-type products or 3–10 mg for semaglutide-type products, that must be dissolved before any volume can be drawn.
Because the vial is punctured repeatedly, the diluent must be preserved. Bacteriostatic water is water for injection with 0.9% benzyl alcohol, which suppresses bacterial growth between draws; unpreserved sterile water suits a single draw only. US Centers for Disease Control and Prevention (CDC) guidance is to date a multi-dose vial on first puncture and discard it within 28 days unless the manufacturer states otherwise [22]. The bacteriostatic water vs sterile water article sets out the difference, and the storage and shelf-life guide explains the 28-day rule.
The core formula
Concentration (mg/mL) = vial content (mg) ÷ diluent volume (mL). To convert to micrograms, multiply by 1,000. On a U-100 insulin syringe, 100 units equal 1 mL, so one unit is 0.01 mL and delivers concentration × 10 mcg.
| Vial | Bacteriostatic water added | Concentration | Per unit (U-100 syringe) |
|---|---|---|---|
| 5 mg | 2 mL | 2.5 mg/mL (2,500 mcg/mL) | 25 mcg |
| 10 mg | 2 mL | 5 mg/mL (5,000 mcg/mL) | 50 mcg |
| 15 mg | 3 mL | 5 mg/mL (5,000 mcg/mL) | 50 mcg |
| 3 mg | 1.5 mL | 2 mg/mL (2,000 mcg/mL) | 20 mcg |
The full tables, including how to plan a diluent volume so that a vial is used up within 28 days, are in the GLP-1 reconstitution protocols article. Multi-dose vials need a preserved diluent: Baclabs supplies UK-stocked bacteriostatic water in 30 mL vials, and the reconstitution guide walks through the arithmetic for any peptide.
What the evidence does and does not tell you
The evidence for semaglutide, tirzepatide and liraglutide rests on tens of thousands of trial participants and years of pharmacovigilance, but it applies to licensed, quality-assured products at licensed doses, not to a vial of unknown provenance carrying the same name. Retatrutide and CagriSema have phase 3 efficacy data but no approved label and no long-term safety database. Dose figures given for investigational compounds in this cluster are the doses studied in the cited trials, not recommendations.
Frequently asked questions
What are GLP-1 peptides?
GLP-1 peptides are engineered analogues of glucagon-like peptide-1, a gut hormone that increases insulin secretion, slows gastric emptying and reduces appetite. Liraglutide and semaglutide act on the GLP-1 receptor alone; tirzepatide also activates the GIP receptor; retatrutide adds the glucagon receptor; and CagriSema pairs semaglutide with the amylin analogue cagrilintide.
Which GLP-1 medicine gives the most weight loss?
Among licensed products, tirzepatide. In the direct SURMOUNT-5 comparison, tirzepatide produced 20.2% mean weight loss at 72 weeks against 13.7% for semaglutide [8]. Investigational retatrutide reported 28.3% at 80 weeks in TRIUMPH-1 [9], but it is not yet approved anywhere and its safety profile is still being assessed.
Is retatrutide available in the UK?
No. Retatrutide has no marketing authorisation in the UK or any other country as of September 2026. Lilly has indicated a US regulatory submission in early 2027. Products sold online as retatrutide are unlicensed, and the MHRA has seized such products in enforcement operations during 2025 and 2026 [20][21].
Do GLP-1 peptides need bacteriostatic water?
Licensed pens are pre-mixed and need no diluent. Lyophilised research vials do, and because they are drawn from more than once, the diluent should be preserved. Bacteriostatic water contains 0.9% benzyl alcohol for that purpose, and an opened multi-dose vial is conventionally used for up to 28 days [22].
What are the main side effects of GLP-1 medicines?
Nausea, vomiting, diarrhoea and constipation, most often during dose escalation. Less common but serious: acute pancreatitis, gallbladder disease and, in people with diabetes, worsening retinopathy. The MHRA strengthened pancreatitis warnings across the class in January 2026 [17]. A rodent thyroid C-cell tumour finding underpins a US boxed warning [18].
References
- Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. Willard FS et al., JCI Insight, 2020. doi:10.1172/jci.insight.140532
- Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial. Jastreboff AM et al., New England Journal of Medicine, 2023. doi:10.1056/NEJMoa2301972
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a phase 2 trial. Lau DCW et al., The Lancet, 2021. doi:10.1016/S0140-6736(21)01751-7
- A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management (SCALE). Pi-Sunyer X et al., New England Journal of Medicine, 2015. doi:10.1056/NEJMoa1411892
- Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). Wilding JPH et al., New England Journal of Medicine, 2021. doi:10.1056/NEJMoa2032183
- Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). Lincoff AM et al., New England Journal of Medicine, 2023
- SURMOUNT-1 results published in the New England Journal of Medicine. Eli Lilly, 2022; Jastreboff AM et al., NEJM, doi:10.1056/NEJMoa2206038
- SURMOUNT-5: Tirzepatide versus Semaglutide for Obesity. American College of Cardiology journal scan of Aronne LJ et al., NEJM, 2025. doi:10.1056/NEJMoa2416394
- Retatrutide delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1). Eli Lilly, May 2026
- Retatrutide successful in two additional Phase 3 obesity trials (TRIUMPH-2 and TRIUMPH-3). Eli Lilly, July 2026
- REDEFINE 1 and REDEFINE 2: Combined Cagrilintide-Semaglutide vs Either Drug Alone or Placebo. American College of Cardiology journal scan of Garvey WT et al. and Davies MJ et al., NEJM, 2025. doi:10.1056/NEJMoa2502081; doi:10.1056/NEJMoa2502082
- Wegovy FlexTouch solution for injection in pre-filled pen, Summary of Product Characteristics. Novo Nordisk, emc, 2026
- Ozempic 0.25 mg solution for injection in pre-filled pen, Summary of Product Characteristics. Novo Nordisk, emc
- Mounjaro KwikPen 2.5 mg solution for injection in pre-filled pen, Summary of Product Characteristics. Eli Lilly, emc, 2026
- Saxenda 6 mg/mL solution for injection in pre-filled pen, Summary of Product Characteristics. Novo Nordisk, emc
- Interim commissioning guidance: NICE TA1026 tirzepatide. NHS England, 2025
- GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists: strengthened warnings on acute pancreatitis. MHRA Drug Safety Update, January 2026
- WEGOVY (semaglutide) injection, US Prescribing Information. FDA, 2025
- Retatrutide delivered weight loss of up to an average of 71.2 lbs with relief from osteoarthritis pain (TRIUMPH-4). Eli Lilly, December 2025
- UK regulators seize illegal weight loss drugs. Pharmaceutical Technology, October 2025
- Two arrested during the MHRA’s largest ever seizure of unlicensed weight loss medicines. MHRA / GOV.UK, May 2026
- Preventing Unsafe Injection Practices. US Centers for Disease Control and Prevention
Disclaimer: This content is for educational purposes only and does not constitute medical advice. Bacteriostatic water is supplied for reconstitution of substances intended for research and for use as directed by a healthcare professional. Peptides and medicines discussed here may be unlicensed in the UK or prescription-only; consult a qualified clinician before using any medicine. Baclabs does not sell peptides.