Mercedes had been told by her doctor that she could be prescribed a GLP‑1 weight‑loss injection in 2024. The news overwhelmed her: "[When] she said yes, I cried in her office. And I didn’t really stop crying for a week," she recalled. For many patients, these drugs have represented hope after years of failed attempts to lose weight; for Mercedes and others, that hope has sometimes ended in fresh disappointment.
GLP‑1 receptor agonists — drugs that mimic a gut hormone involved in appetite and glucose control — have been hailed as a gamechanger in obesity care because they can substantially reduce appetite and body weight for many users. But clinicians report that a minority of patients derive negligible benefit, and some people describe intense continued cravings, likened by some to "heroin withdrawal" in the way they experience persistent urges to eat.
There is no single explanation for why some patients do not respond. Doctors and researchers point to multiple possible factors, including biological variability in how individuals' appetite and metabolism respond to the medication, differences in dosing or duration of treatment, coexisting medical conditions or medications that blunt effect, and behavioural or psychological issues such as disordered eating that may require additional interventions. A growing consensus among clinicians is that lack of response is often multifactorial and that more research is needed to tease apart the drivers of non‑response.
For patients who do not benefit, clinicians take a range of approaches: reassessing the diagnosis, reviewing other medicines, adjusting dose or delivery where appropriate, and integrating dietary, behavioural and psychological support. Some specialists emphasize the importance of setting realistic expectations before treatment begins and monitoring progress closely so that changes can be made promptly if weight loss stalls.
The emergence of these therapies has highlighted broader challenges in obesity care: demand for effective treatments is rising, but so too are difficult questions about long‑term outcomes, equitable access and how best to help people for whom the drugs do not work. As use of GLP‑1 medications expands, clinicians and researchers say understanding why a minority of patients fail to respond must be a priority to ensure that all patients receive effective, individualized care.