Real-world persistence on GLP-1 receptor agonists and tirzepatide is poor, with many people stopping inside the first year. The reasons are gastrointestinal adverse effects, disappointing efficacy, cost, and fear of rare harms. What follows discontinuation is well described: weight regain and deterioration across several cardiometabolic risk factors.
The argument this review makes goes further. Repeated cycles of starting, stopping and restarting produce fluctuation in both body weight and HbA1c, and each of those fluctuations is itself a risk factor for cardiovascular and microvascular events. Because these drugs are not anti-atherosclerotic and do not stabilise plaque, the period just after stopping may carry a particular risk. The authors are explicit that hard outcome data in people who discontinue are scarce.
So the clinical move is upstream. Before starting, establish that the patient can stay on it — supply, cost, tolerability, and their own expectations. A patient who cannot sustain the drug for years may be better served by a regimen they can sustain than by a cycle of starts and stops, and that judgement belongs at the first consultation rather than the fourth.
- Check affordability and supply before the first prescription, not after the first interruption.
- Treat a request to stop as a consultation, not an administrative act — review what replaces the drug.
- Where cost is the barrier, discuss a sustainable alternative rather than an intermittent course of the same drug.
- Monitor weight and HbA1c for at least six months after any discontinuation.
- In India, out-of-pocket payment for these agents is the rule rather than the exception, which makes the sustainability question sharper here than in the settings most persistence data come from.
Why it matters
The treatment works — the difficult part is what happens when it stops.
Don't overread it
The harm from cycling on and off is inferred from variability research, not demonstrated in a trial of discontinuation.
The statistics, in plain English
This is a narrative review, so there is no pooled effect size to quote. The claim that weight and HbA1c fluctuation raise cardiovascular risk is drawn from other literature, not measured in people who discontinued incretins; the review says plainly that outcome data in that specific group are few.
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