GLP-1s After the Shortage: Branded vs Compounded vs Telehealth — A 2026 Reader

What are GLP-1 Receptor Agonists?

GLP-1 (glucagon-like peptide-1) receptor agonists are a class of medications originally developed for type 2 diabetes that have become the most clinically significant weight management tools available. They work by mimicking the gut hormone GLP-1, which is released after eating, to slow gastric emptying, reduce appetite signalling in the hypothalamus, and increase insulin secretion in a glucose-dependent manner.

The current leading agents in this class are semaglutide (Wegovy for weight management, Ozempic for diabetes — same molecule, different dose and labelling) and tirzepatide (Mounjaro — a dual GLP-1/GIP agonist). Both are prescription-only medicines in the UK regulated by the MHRA.

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How GLP-1s Work: Mechanism of Action

GLP-1 receptors are expressed in the pancreas, brain (hypothalamus and brainstem), stomach, and cardiovascular tissue. Activation produces four key effects relevant to weight and metabolic health:

1. Appetite suppression — signals to the hypothalamus reduce hunger drive, particularly reducing cravings for high-calorie foods.
2. Gastric emptying delay — food moves through the stomach more slowly, extending satiety signals.
3. Glucose-dependent insulin secretion — insulin is released only when blood glucose is elevated, avoiding hypoglycaemia.
4. Glucagon suppression — reduces hepatic glucose output in hyperglycaemic states.

Tirzepatide adds a GIP (glucose-dependent insulinotropic polypeptide) agonist action to all of the above, which appears to amplify weight loss efficacy — explaining why SURMOUNT-1 showed greater mean weight reduction (~20% body weight) than STEP 1 (~15%). ^[1][2]

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Evidence: What the Research Shows

STEP Programme (semaglutide)

The STEP clinical programme (STEP 1–5) established semaglutide 2.4 mg/week as the benchmark intervention. STEP 1 (n=1,961, non-diabetic adults with obesity) showed mean 14.9% body weight reduction vs 2.4% on placebo at 68 weeks. ^[1] STEP 5 (104-week extension) showed maintained weight loss, indicating sustained efficacy.

SURMOUNT-1 (tirzepatide)

SURMOUNT-1 (n=2,539) showed dose-dependent weight loss with tirzepatide 15 mg/week producing ~22.5% mean reduction at 72 weeks — the largest weight reduction demonstrated in a pharmacological RCT at that time. ^[2]

SELECT Trial (cardiovascular outcomes)

The SELECT trial (n=17,604, adults with obesity and established cardiovascular disease, no diabetes) showed that semaglutide 2.4 mg/week reduced major adverse cardiovascular events (MACE) by 20% vs placebo over ~3.3 years. ^[4] This is the first direct evidence of cardiovascular mortality benefit from a weight-management drug independent of diabetes status.

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Dosage and Protocol

Medication	Starting dose	Maintenance dose	Route	Titration
Semaglutide (Wegovy)	0.25 mg/week	2.4 mg/week	Subcutaneous injection	4-week escalation steps over 16–20 weeks
Tirzepatide (Mounjaro)	2.5 mg/week	5–15 mg/week	Subcutaneous injection	4-week escalation; titrate to tolerability

Both require supervised initiation. Nausea and vomiting (common, usually transient) are managed by slow titration.

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Safety, Side Effects, and Drug Interactions

Common: Nausea, vomiting, constipation or diarrhoea (most frequent during dose escalation; typically resolve). Reduced appetite leading to micronutrient deficiency in some patients if diet quality is poor.

Serious: Pancreatitis (rare, reported; pre-existing pancreatitis history is a contraindication). Thyroid C-cell tumours (seen in rodent models at high doses; not demonstrated in human RCTs but a labelled warning — contraindicated with personal/family history of medullary thyroid carcinoma or MEN2 syndrome). Gallbladder disease (increased gallstone risk associated with rapid weight loss, not drug-specific).

Drug interactions: No clinically significant interactions via CYP pathways. Delayed gastric emptying may affect absorption timing of oral medications — take time-sensitive drugs (e.g. thyroid hormone, oral contraceptives) at standardised times relative to meals.

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UK Regulatory Status

Both semaglutide (Wegovy) and tirzepatide (Mounjaro) hold MHRA marketing authorisation for chronic weight management in adults with BMI ≥30 kg/m², or ≥27 kg/m² with a weight-related comorbidity. Both are Prescription-Only Medicines (POM).

Compounded semaglutide is not permitted in the UK. The MHRA has no equivalent of the US FDA shortage-provision pathway that allowed US compounding pharmacies to produce semaglutide during the shortage period. Any “compounded semaglutide” marketed to UK patients is operating outside MHRA authorisation. The FSA does not regulate prescription medicines — this falls entirely within MHRA scope.

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How to Stack GLP-1s with Other Protocols

GLP-1s are metabolic interventions with implications for the whole protocol stack:

Rapamycin: Both drugs affect metabolic pathways (mTOR/AMPK axis for rapamycin; insulin/glucose for GLP-1s). No known harmful interaction; some practitioners combine them. See our rapamycin protocol guide.

Exercise: GLP-1-induced weight loss includes lean mass loss in some patients. Resistance training alongside GLP-1 therapy is recommended by most prescribers to preserve muscle mass. Protein intake should be actively managed — target ≥1.2 g/kg of target body weight.

Continuous glucose monitoring (CGM): Highly complementary. CGM data allows real-time assessment of glycaemic response to meals and exercise, informing dose timing decisions and dietary choices alongside GLP-1 therapy.

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Find a UK Practitioner Who Specialises in GLP-1 Protocols

GLP-1 prescribing in the UK is available through NHS obesity services (qualifying criteria apply) and a growing number of private telehealth and clinic-based services. Proven Longevity’s directory includes practitioners who offer supervised GLP-1 protocols with full metabolic workup and monitoring.

Find a UK GLP-1 specialist →

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Frequently Asked Questions

Is compounded semaglutide available in the UK? No. The UK compounding pathway does not permit copies of authorised medicines. Patients in the UK must use MHRA-authorised branded products (Wegovy, Ozempic for relevant indications) prescribed by a licensed clinician.

How does Mounjaro (tirzepatide) compare to Wegovy (semaglutide)? In head-to-head terms, SURMOUNT-vs-STEP data suggests tirzepatide produces greater mean weight loss (~20–22% vs ~15% for semaglutide). Direct head-to-head RCTs are ongoing. Tirzepatide’s dual mechanism (GLP-1 + GIP) appears to drive superior efficacy in clinical trials. Individual response varies.

Does Wegovy reduce cardiovascular risk? Yes — the SELECT trial showed a 20% reduction in MACE for semaglutide 2.4 mg/week in adults with obesity and established cardiovascular disease over ~3.3 years. This is independent of the blood sugar effects. ^[4]

Will I regain weight when I stop? Rebound weight gain after stopping GLP-1 therapy is well-documented in the trial data — most of the lost weight returns within 1–2 years of discontinuation without lifestyle maintenance. GLP-1s are most effective as long-term management tools, not short-term interventions.

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References

1. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989–1002. PubMed 33567185
2. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205–216. PubMed 35658024
3. Ryan DH, et al. Long-term weight loss effects of semaglutide in STEP 5 trial. Lancet Diabetes Endocrinol. 2021;9(5):271–280. PubMed 33690850
4. Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389(24):2221–2232. PubMed 37952131
5. US FDA. Compounded Drug Products That Are Copies of Commercially Available Drug Products. FDA guidance
6. Novo Nordisk. Wegovy (semaglutide) UK prescribing information. eMC product 14106
7. Eli Lilly. Mounjaro (tirzepatide) UK prescribing information. eMC product 15104
8. MHRA. Semaglutide for weight management — prescribing update. 2024. MHRA guidance