What is the difference between adherence and persistence?

Adherence is taking treatment as directed while on it; persistence is still being on it later. Someone can be adherent for months and then stop.

Why does persistence matter so much for obesity?

The condition is chronic and stopping is followed by weight regain, so benefit depends on continued treatment.

How does this relate to estimands?

The treatment-policy estimand counts everyone including those who stopped, which is the same distinction applied inside a trial.

GLP-1 & Incretin Science

How Many People Are Still Taking It a Year Later

JMWritten & reviewed by Jack Muncaster · Founder, UK PeptidesLast reviewed 2026-08-232 cited sources

Adherence describes whether treatment is taken as intended; persistence describes whether it is continued over time. Dziewierz and colleagues reviewed international real-world evidence on both for GLP-1-based therapies in Nutrients in May 2026.

Key facts

Adherence: Taking treatment as intended
Persistence: Continuing over time
2026 review: Dziewierz (PMID 42280404)
Earlier real-world work: Mody 2018 (PMID 29271258)
Why it matters: Decides whether trial results generalise
Connected concept: Treatment-policy estimand

Two words that are not synonyms

Adherence asks whether someone takes a treatment as directed while they are on it. Persistence asks whether they are still on it at all after some period. A person can be perfectly adherent for three months and then stop, which is good adherence and poor persistence. Conflating them obscures which problem a population actually has.

Why persistence is the harder problem here

Obesity is chronic, so benefit depends on continued treatment, and stopping is followed by weight regain. That makes persistence not merely desirable but the condition on which the entire benefit rests. A therapy with excellent efficacy and poor persistence delivers much less across a population than its trial figures suggest.

Research material referenced

Retatrutide 10mg — third-party HPLC tested

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Why trials systematically overstate what a population will see

Trial participants are selected, monitored, supported and reminded, and receive treatment free of charge. None of that applies in routine care. The gap this produces is the difference between efficacy — what a drug does under trial conditions — and effectiveness, what it does in practice, and it is why the two are given separate names.

The direct link to estimands

This is the same distinction the efficacy and treatment-policy estimands formalise. The efficacy estimand describes what happens if everyone adheres; the treatment-policy estimand counts everyone regardless. The gap between them within a trial is a preview of the larger gap between a trial and a population, and it is why a figure quoted without its estimand is uninterpretable.

What drives discontinuation

Cost, gastrointestinal tolerability, supply, and the ordinary attrition of any chronic regimen. Dziewierz and colleagues examine the role of nutritional and lifestyle support alongside the pharmacology, which reflects a view that persistence is not solely a property of the drug but of what surrounds its use.

Why this is not a criticism of the compounds

Poor persistence is a feature of chronic treatment generally rather than of these drugs specifically — Mody and colleagues were examining the same questions for this class back in 2018. It sets an upper bound on population benefit, and knowing that bound is part of reading the trial literature honestly rather than an argument against it.

Extended research context

The GLP-1 & Incretin Science deep dive

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.

Research applications

▸Comparing incretin and amylin compounds on a like-for-like basis
▸Interpreting estimands, thresholds and placebo-adjusted figures in trial reports
▸Tracking the obesity pipeline across sponsors and jurisdictions
▸Understanding receptor pharmacology behind GLP-1, GIP, glucagon and amylin
▸Distinguishing licensed medicines from investigational compounds

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 research-handling mistakes

Learnt from thousands of researcher orders across our UK labs.

✗ Comparing headline percentages across different trials

Fix: Population, duration, estimand and comparator all differ; the numbers are not interchangeable.

✗ Quoting the larger of two figures from the same trial

Fix: Name the estimand. Efficacy and treatment-policy answer different questions.

✗ Treating peak reduction as a durable outcome

Fix: Substantial regain follows cessation across the class; peak figures describe a maintained state.

✗ Assuming an oral route means a weaker mechanism

Fix: 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

Fix: Most of this pipeline holds no authorisation anywhere; mazdutide is approved only in China.

Continue researching

Peer-reviewed guides, comparators and matched reference materials.

Frequently asked questions

What is the difference between adherence and persistence?: Adherence is taking treatment as directed while on it; persistence is still being on it later. Someone can be adherent for months and then stop.
Why does persistence matter so much for obesity?: The condition is chronic and stopping is followed by weight regain, so benefit depends on continued treatment.
How does this relate to estimands?: The treatment-policy estimand counts everyone including those who stopped, which is the same distinction applied inside a trial.

Primary sources & clinical trials

Peer-reviewed research and registered trials from PubMed, ClinicalTrials.gov, PubChem, FDA and NIH. All links open in a new tab and point to the primary source, so every claim can be verified at origin.

Written and reviewed by

Jack Muncaster · Founder, UK Peptides

Jack founded UK Peptides in Manchester after repeatedly receiving research compounds with missing or recycled paperwork. He is responsible for supplier selection, batch release decisions and the content published in this research library. Every article here is sourced to primary literature and every product page to a signed third-party certificate.

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