The Weight Loss Family Tree

Too many names

Liraglutide. Semaglutide. Tirzepatide. Retatrutide. Cagrilintide. Mazdutide. Survodutide. If you have tried to follow weight loss drug news in the past few years, the names blur together.

One genuinely helpful thing about The Complete Guide to Peptides is that, because it is organised as an encyclopedia, all of these appear in the same format. Line them up and a clear family tree appears. Once you see it, every new drug announcement makes sense.

The root: GLP-1

Everything starts with one hormone. GLP-1 (glucagon-like peptide-1) is released by your gut when you eat. The book's entries describe its effects consistently:

• It boosts insulin release, but only when blood sugar is high (glucose-dependent), which is why it carries low risk of hypoglycaemia on its own.
• It suppresses glucagon, a hormone that raises blood sugar.
• It slows how fast the stomach empties.
• It signals fullness to the brain.

The problem with natural GLP-1 is that it lasts only a couple of minutes in the blood before being broken down. So the first job for drug designers was to make versions that last.

Branch 1: longer lasting GLP-1

Liraglutide was the first widely used one. The book gives the standard schedule: start at 0.6 mg daily and increase gradually up to 3 mg daily. That is a daily injection because it lasts about a day.

Semaglutide was engineered to last about a week. The book gives the weekly schedule, starting at 0.25 mg and rising, with 2.4 mg used for weight management. It also mentions, in its myths section, that an oral form exists for type 2 diabetes, which is correct and a real feat of drug design.

Both are approved medicines, and the book's entries note their prescription status and their known risks: gastrointestinal effects, rare pancreatitis and gallbladder problems, and the thyroid C-cell tumour signal seen in rodent studies.

Branch 2: add a second hormone

The next idea was to hit more than one receptor.

Tirzepatide acts on GLP-1 receptors and also on receptors for GIP (glucose-dependent insulinotropic polypeptide), another gut hormone. It has produced greater average weight loss than semaglutide in trials. It is approved.

Mazdutide combines GLP-1 with the glucagon receptor. That might sound strange, since glucagon raises blood sugar. But glucagon also increases energy expenditure and fat burning in the liver. The GLP-1 side keeps blood sugar in check while the glucagon side adds a metabolic push. The book describes it as a dual GLP-1 and glucagon agonist. It has been in trials, largely in China, and has been approved there.

Survodutide follows the same GLP-1 plus glucagon approach and has been in trials, including for fatty liver disease.

Branch 3: add a third

Retatrutide acts on all three: GLP-1, GIP and glucagon. The book correctly describes it as a multi-agonist targeting all three receptors. It has been in late-stage trials and has produced some of the largest average weight losses of any drug tested so far.

(One small slip: in retatrutide's research recommendations, the book suggests searching "Retatrutide dual receptor agonist". It is a triple agonist. Searching that phrase will still find results, but it is a nice example of why you check the details.)

A different trunk: amylin

Cagrilintide comes from a different hormone family entirely. It mimics amylin, a hormone released by the pancreas alongside insulin. Amylin also slows stomach emptying and increases fullness, but through different brain pathways from GLP-1.

The book notes it was designed to complement GLP-1 drugs, and mentions CagriSema, a combination of cagrilintide with semaglutide, which has been tested in large trials. That combination idea, pairing two different fullness signals, is one of the more interesting directions in the field.

Reading the family tree

Here is the pattern once you see it:

Every new name you read about will fit somewhere in this tree. Ask "which hormones does it mimic?" and you immediately know roughly what to expect from it.

The important distinction

What the family tree also shows is a sharp line between approved drugs and investigational ones. The book gives dosing for all of them in the same format. For the approved ones, those doses come from prescribing information and match what doctors use. For the investigational ones, dosing is still being worked out in trials, and anyone using them outside a trial is using an unapproved product of unknown origin.

That difference is not a technicality. Approved drugs come from regulated manufacturing with guaranteed content and sterility. A vial labelled "retatrutide" bought online comes with neither.

The takeaway

This part of the book is useful precisely because it puts the whole family in one place. Understanding that nearly all of modern obesity pharmacology branches from a single gut hormone, and then adds second and third signals, makes the headlines far easier to follow.

It also makes the practical choice clearer. If weight is a medical problem for you, several approved members of this family exist, and a doctor can prescribe them. The newer branches are exciting and worth watching. They are not yet on the shelf.

This series reviews a consumer book, not a clinical guideline. Many compounds it discusses are not approved for human use in most countries. Nothing here is medical advice or a recommendation to use any substance. Speak to a qualified clinician before starting anything.