Why Weight-Loss Drugs Fail Some People — and What Can Be Done

Genetics may compound the problem. A recent study in Nature of nearly 28,000 people taking GLP-1 drugs found that some carried a genetic variant making them more likely to experience nausea and vomiting. Even so, Taylor argues that with an appropriate dose and careful clinical guidance, the drugs should overcome genetic obstacles.

What role do diet, exercise and sleep play?

Patients are often told to maintain a healthy diet alongside treatment — and for good reason. Those who continue eating highly calorific foods will see only a marginal impact from the drugs.

Exercise matters too. A 2024 study in eClinicalMedicine found that people taking GLP-1 drugs lost more weight, and were more likely to keep it off long term, when they combined treatment with supervised exercise rather than relying on the drugs alone.

Sex may also influence outcomes. A study in Diabetes Care found that women lost more weight than men while taking the drugs — possibly because women naturally produce more of the body's own GLP-1 hormone, and because oestrogen increases the body's sensitivity to insulin (the hormone that regulates blood sugar). Taylor, however, is sceptical. "I wouldn't be surprised if it was slightly less effective in men," he says, but sex is likely to play "only a minor role".

Sleep deprivation could also be a factor: one study found it exerts a "mild, but discernible effect" on GLP-1 concentrations in healthy men. Taylor again cautions against drawing a direct line. "The effect of sleep on the body in terms of metabolic effects is trivial," he argues. In heavier individuals, poor sleep is often caused by excess weight — fat around the throat triggering snoring or even sleep apnoea (interrupted breathing during sleep) — rather than the reverse. "If a person injects the GLP-1s consistently, there will probably be just an improvement in sleep," he says.

How can patients improve their odds?

For an unfortunate minority, evidence suggests no change in dosage will make a difference. For everyone else facing controllable obstacles, the first step is honest communication. Doctors must explain how the drugs work and warn that nausea is likely at first — and that it fades with continued use, Taylor says. This is especially important for the many people taking the drugs without medical supervision.

"If this is not explained — and especially so if people are taking these drugs without medical supervision, as many people are — then this is a really potent issue," he said. "Individuals vary in their response to drugs," but it is the doctor's responsibility to "ensure that people are aware of what's about to happen."

The message, in short: the injection is only part of the equation.