What "GLP-1 peptide" actually means
GLP-1 stands for glucagon-like peptide-1, a hormone your gut releases after a meal. It signals satiety, slows stomach emptying, and nudges the pancreas to release insulin only when blood sugar is high. Drugs that mimic GLP-1 were first developed for type 2 diabetes; the weight-loss effect turned out to be large enough that they are now prescribed primarily for obesity.
The category has since expanded. Tirzepatide is a dual agonist: it hits both the GLP-1 and GIP receptors. Retatrutide adds glucagon receptor activity, making it a "triple G" agonist. Each extra receptor changes the side-effect profile and, in trials, appears to push mean weight loss higher.
The three compounds at a glance
| Compound | Receptors | Half-life | Key trial | Mean weight loss |
|---|---|---|---|---|
| Semaglutide | GLP-1 only | ~7 days | STEP-1 | ~15% at 2.4 mg over 68 weeks |
| Tirzepatide | GLP-1 + GIP | ~5 days | SURMOUNT-1 | ~21% at 15 mg over 72 weeks |
| Retatrutide | GLP-1 + GIP + glucagon | ~5–7 days | Phase 2 | ~24% at 12 mg over 48 weeks |
These figures are trial averages, not predictions for any individual. Retatrutide data are phase 2 and may change after larger, longer studies.
Dosing and titration overview
All three are once-weekly subcutaneous injections. The dose is raised slowly over weeks or months to reduce nausea and allow the gut to adapt. Starting at a high dose usually produces intolerable side effects.
| Compound | Starting dose | Typical escalation | Maintenance range |
|---|---|---|---|
| Semaglutide | 0.25 mg weekly | Increase every 4 weeks | 1.0–2.4 mg weekly |
| Tirzepatide | 2.5 mg weekly | Increase by 2.5 mg every 4 weeks | 5–15 mg weekly |
| Retatrutide | 2 mg weekly | Escalate over several weeks | Up to 12 mg weekly (phase 2) |
These are educational summaries of published protocols, not personalised dosing instructions. Any use of these medicines requires a qualified prescriber.
Side effects and muscle preservation
Gastrointestinal effects are the headline issue. Nausea, vomiting, diarrhoea and constipation are common, usually peak after a dose increase, and often settle over time. Gallbladder disease, pancreatitis, and severe dehydration are less common but require medical attention.
A separate concern is body composition. When people lose weight rapidly, lean mass often falls alongside fat. Resistance training two to three times per week, protein intake around 1.2–1.6 g per kg body weight, and a moderate calorie deficit rather than an aggressive one are the standard mitigations. This applies to all three compounds.
Who should not use GLP-1 peptides
Personal or family history of medullary thyroid carcinoma or MEN2 is a contraindication. They should also be avoided in pregnancy and usually stopped before planned pregnancy. People with a history of pancreatitis, severe gallbladder disease, or type 1 diabetes need specialist review. Because GLP-1 agonists slow gastric emptying, they can alter absorption of other oral medicines.
Frequently asked questions
What is a GLP-1 peptide?
GLP-1 peptides are molecules that mimic glucagon-like peptide-1, a gut hormone released after eating. They slow gastric emptying, suppress appetite, and increase insulin release in a glucose-dependent way. Semaglutide, tirzepatide and retatrutide are the best-known examples. Tirzepatide also activates GIP; retatrutide adds glucagon receptor activity.
Which is more effective for weight loss: semaglutide, tirzepatide or retatrutide?
Head-to-head trial data is limited, but phase-3-equivalent results suggest a rough hierarchy. Semaglutide 2.4 mg produced about 15% mean weight loss over 68 weeks. Tirzepatide reached up to about 21% at 15 mg. Retatrutide phase-2 data showed up to about 24% at 12 mg. Larger, longer retatrutide trials are needed to confirm durability and safety.
What are the main side effects of GLP-1 peptides?
Nausea, vomiting, diarrhoea and constipation are the most common dose-dependent effects. Gallbladder issues, pancreatitis, and low blood sugar when combined with other diabetes medicines are rarer but serious. All three drugs carry a warning for personal or family history of medullary thyroid carcinoma.
Do GLP-1 peptides cause muscle loss?
Weight lost on any calorie deficit includes some lean mass. Trials of semaglutide and tirzepatide show that roughly 30–40% of total weight lost can be lean tissue, which is higher than ideal. Resistance training, adequate protein intake, and sufficient calories are the usual mitigation strategies.
What is the difference between GLP-1, GIP and glucagon agonism?
GLP-1 mainly suppresses appetite and slows stomach emptying. GIP may improve insulin sensitivity and lipid handling, and appears to reduce nausea when co-activated. Glucagon increases energy expenditure and fat oxidation. Tirzepatide combines GLP-1 and GIP; retatrutide adds glucagon to make a 'triple G' agonist.