UK Peptides · Research Index

Every GLP-1 & Incretin Science Question Answered, in 119 Studies

The incretin and amylin compound landscape, and how to read the trial data behind it.

119 referenced articles

Open research questions

  • Which weight-loss compound produces the largest reduction?
  • What is the difference between CagriSema and amycretin?
  • What is an amylin receptor agonist?
  • How much weight is regained after stopping a GLP-1?
  • Why does CagriSema report two different percentages?
  • Why is orforglipron less effective than retatrutide?

Deep dive: the two routes to a bigger effect

Every compound trying to beat GLP-1 alone has taken one of two routes. The first adds more receptors from the same hormone family — GIP in tirzepatide, GIP and glucagon in retatrutide. The second adds a non-incretin satiety hormone, which in practice means amylin: CagriSema combines cagrilintide with semaglutide, and amycretin engages both receptors from one molecule. Both routes work, because they recruit signalling pathways that do not fully overlap. Neither has escaped the constraint that binds all of them, which is that gastrointestinal tolerability worsens as effect size grows.

Deep dive: why a percentage is not a result

The most-quoted numbers in this field are the least comparable. REDEFINE 1 reported 22.7% and 20.4% for the same compound in the same trial — the first among participants who adhered to treatment, the second across everyone randomised. TRIUMPH-1 reported 28.3% in an uncomplicated obesity population while TRIUMPH-3 reported up to 22.6% in adults with established cardiovascular disease, using the same compound. Before any two figures can be compared they have to match on estimand, population, duration, comparator and whether the number is placebo-adjusted. Most published comparisons match on none of them.

Deep dive: what happens after the trial stops

Every headline figure describes weight while treatment continues. The STEP-1 extension found that a year after semaglutide was stopped, participants had given back roughly two-thirds of what they lost, moving from 17.3% mean reduction to a net 5.6% — though average weight remained below baseline and nearly half stayed at least 5% down. Meta-analysis puts regain at around 0.8 kg per month. This is why maintenance studies such as TRIUMPH-6 matter more to the field's future than another two points of peak reduction.

Handling checklist

  • Identify which estimand a quoted percentage comes from before citing it
  • Check the trial population and baseline BMI against the comparison you are making
  • Confirm the duration and whether the reduction curve had plateaued
  • Read discontinuation rates alongside efficacy figures
  • Verify every NCT identifier against ClinicalTrials.gov rather than secondary reporting

Common mistakes

Comparing headline percentages across different trials
Population, duration, estimand and comparator all differ; the numbers are not interchangeable.
Quoting the larger of two figures from the same trial
Name the estimand. Efficacy and treatment-policy answer different questions.
Treating peak reduction as a durable outcome
Substantial regain follows cessation across the class; peak figures describe a maintained state.
Assuming an oral route means a weaker mechanism
Route and receptor count are independent. Orforglipron is weaker because it hits one receptor, not because it is a tablet.
Reading investigational compounds as available treatments
Most of this pipeline holds no authorisation anywhere; mazdutide is approved only in China.

Related reading

Reference material for laboratory research. Not medical advice, and not an offer to supply any compound for human use.