Semaglutide
The most rigorously trialled compound in the peptide space. Multiple large phase 3 randomized trials with cardiovascular outcome data.
Metabolic & Weight
Liraglutide
The first once-daily GLP-1 analogue to reach broad approval. Cardiovascular outcome data from LEADER established the class safety precedent.
Overview
Liraglutide is a modified copy of the gut hormone GLP-1. It prompts insulin release when blood sugar is high, slows stomach emptying, and reduces appetite. The modification is a fatty acid chain that makes it stick to albumin in the blood, extending its life from minutes to around half a day. That still means daily injection, which is the main practical difference from the weekly compounds that followed it.
Liraglutide is an acylated GLP-1 analogue with 97% homology to native GLP-1(7-37). It carries a Lys34Arg substitution and a C16 palmitic acid attached via a gamma-glutamyl spacer at Lys26. Albumin binding and self-association into heptameric micelles at the injection site slow subcutaneous absorption and confer partial DPP-4 protection, producing a terminal half-life of roughly 13 hours. Receptor pharmacology is conventional GLP-1R Gs coupling: adenylate cyclase activation, cAMP elevation, PKA and Epac2 signalling, glucose-dependent insulin exocytosis, glucagon suppression, delayed gastric emptying, and central anorectic signalling at arcuate POMC/CART neurons with indirect GABAergic inhibition of NPY/AgRP neurons.
Research areas
MetabolicObesityCardiovascularNeurodegeneration
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| 0.6 mg daily for one week, escalating by 0.6 mg weekly to 3.0 mg daily for weight management | SCALE Obesity and Prediabetes trial protocol (Pi-Sunyer et al., NEJM 2015) |
| 1.2 mg or 1.8 mg daily maintenance for glycaemic control in type 2 diabetes | LEADER trial protocol (Marso et al., NEJM 2016) |
Trial status
Approved. Phase 3 complete across LEAD, SCALE and LEADER programmes.
Phase 3 — LEAD programme
CompletedSix trials establishing glycaemic efficacy in type 2 diabetes across monotherapy and combination settings.
Phase 3 — SCALE Obesity and Prediabetes
Completed3,731 participants without diabetes. Mean weight change of -8.4 kg on liraglutide 3.0 mg vs -2.8 kg on placebo at 56 weeks.
Phase 3 — LEADER
Completed9,340 patients with type 2 diabetes at high cardiovascular risk. Primary composite outcome in 13.0% on liraglutide vs 14.9% on placebo over a median 3.8 years.
Reported safety signals
- Gastrointestinal adverse events are the most common and are the principal driver of discontinuation.
- Boxed warning for thyroid C-cell tumours based on rodent carcinogenicity studies.
- Higher rates of gallbladder-related events were reported in the SCALE weight management programme.
Primary sources
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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