Learn: peptides, GLP-1 medicines and how to read the evidence

GLP-1 basics

GLP-1 (glucagon-like peptide-1) is a hormone the gut releases after a meal. It tells the pancreas to release insulin when blood glucose is high, slows how quickly the stomach empties and signals fullness to the brain. GLP-1 medicines mimic or amplify that signal for far longer than the natural hormone lasts, which is why they help with blood glucose and with appetite and weight.

Mechanisms: receptors and molecule types

A medicine's mechanism is which receptors it acts on: GLP-1 alone, GLP-1 plus GIP, GLP-1 plus glucagon, amylin, or combinations. Its molecular type is what it is chemically: most GLP-1 medicines are peptides, chains of amino acids given by injection or, with special formulation, by mouth; orforglipron is a small molecule tablet. GLPInfo records the two separately because they answer different questions.

How trials work

Medicines reach approval through phased trials. Phase 1 tests safety in small groups; Phase 2 looks for a dose and an effect; Phase 3 tests the medicine against a placebo or a comparator in large groups over months or years, with a primary endpoint agreed in advance. A registry entry (for example on ClinicalTrials.gov) records the design and the estimated and actual completion dates. GLPInfo records each trial and each dose arm separately; a result belongs to its own arm and population.

Interpreting results

Weight change is not linear and trial populations, durations and methods differ, so GLPInfo never ranks unrelated trials by weight loss per week. A head-to-head trial, where two medicines are compared in the same study, is different from a cross-trial observation. Relative risk reduction (a percentage change in the rate of an event) and absolute risk reduction (the change in how many people out of a hundred have the event) tell different stories and are labelled as such.

Safety

The most common side effects of GLP-1 medicines are gastrointestinal: nausea, vomiting, diarrhoea and constipation, usually worst during dose escalation. Rarer but important risks are described in each official label. Safety updates from regulators are shown on the timeline with a warning treatment, a source and a date. Nothing on GLPInfo replaces the current label or a prescriber's advice.

Approval versus access

Regulatory approval means a regulator has licensed a medicine for a stated indication and population in its jurisdiction. Launch means the company has made it commercially available there. Funded access means a payer, such as the NHS through NICE guidance, covers it for a defined group. These are three different milestones; GLPInfo shows them separately, and an approval in one jurisdiction says nothing about another.

How GLPInfo estimates timing

A company target is a dated sponsor statement; a regulator target is an official decision date; a GLPInfo estimate is an editorial range built from the remaining work (trial completion, filing, validation, review with clock stops) with its assumptions, sources, reviewer and review date shown. Confidence in timing is qualitative and never a probability of approval. An overdue estimate becomes Timing under review; it never becomes an approval. Where there is no responsible range, the tracker says Timing unknown and names the next observable milestone.

Glossary

Indication

The condition and population a medicine is licensed to treat, as written in its label.

Formulation

The physical form and strength of a medicine, for example a once-weekly injection or a once-daily tablet.

Primary endpoint

The main outcome a trial was designed to measure, fixed before the trial starts.

Comparator

What the medicine is tested against in a trial: a placebo or another treatment.

Estimand

A precise statement of what a trial result is estimating, including how discontinuations are handled.

PDUFA date

In the US, the FDA's target date for acting on an application under the Prescription Drug User Fee Act. A target, not a guarantee of approval.

CHMP opinion

The recommendation of the EMA's Committee for Medicinal Products for Human Use. The European Commission makes the final authorisation decision.

MHRA

The UK's Medicines and Healthcare products Regulatory Agency.

NICE

The National Institute for Health and Care Excellence, whose guidance shapes NHS funding in England.

Label update

A change to a medicine's official product information, which may add data without adding a new indication.