Why Ozempic Results Depend on How Patients Overeat

Doctors who prescribe medicines such as Ozempic have become adept at forecasting certain effects.

They can reasonably expect blood glucose to fall and body weight to decrease.

Far more difficult to foresee is why, after a year of treatment, some people achieve striking results while others taking the identical medicine at the same dose see much smaller benefits.

A 12-month Japanese study indicates that the answer may not lie in the medicine itself, but in the way each patient overeats.

A difficult question to answer

Ozempic, Wegovy and Mounjaro have changed treatment for many people living with type 2 diabetes.

Yet outcomes vary considerably. Some patients lose 9 kg and see their readings settle, whereas others experience only limited change after a year on the same treatment.

Researchers led by Professor Daisuke Yabe at Kyoto University and Dr Takehiro Kato at Gifu University monitored 92 adults with type 2 diabetes during their first 12 months taking these medicines.

Across hospitals in Japan’s Gifu Prefecture, the team examined whether a person’s usual pattern of overeating could identify those most likely to benefit.

How GLP-1 drugs alter eating behaviour

GLP-1 medicines imitate a hormone released by the gut following food intake. They encourage the pancreas to produce more insulin while slowing the rate at which the stomach empties.

They also seem to curb appetite via brain signals, although the extent to which this effect leads to weight loss differs greatly between individuals.

Appetite is influenced by several triggers, including the appearance and aroma of food, as well as stress and sadness. A medicine that dampens one trigger may have little effect on the others.

Three distinct eating patterns

Participants were classified using a validated questionnaire that assessed their tendency to overeat. It identified three patterns.

The first, external eating, means eating because food appears or smells appealing despite not feeling hungry.

The second, emotional eating, involves using food to manage stress, sadness or boredom. The third, restrained eating, refers to consciously trying to limit food consumption.

Most people display a combination of all three. The researchers wanted to establish whether that combination influenced how effectively the medicine worked over an entire year.

Monitoring patients for a year

The participants began treatment with one of four GLP-1 medicines: oral or injectable semaglutide, dulaglutide or liraglutide.

The researchers measured body weight, body fat, blood glucose, cholesterol and dietary intake at baseline, after three months and after 12 months.

At the end of the year, participants had lost an average of roughly 3.6 kg and reduced their body-fat percentage by almost 2 percentage points.

HbA1c fell from 8.2 to 7.0. HbA1c is a standard indicator of average blood glucose control over several months.

Muscle mass remained unchanged throughout, a notable result given persistent concerns about muscle loss with these medicines. Cholesterol measures also improved.

External eating and GLP-1 drugs stand apart

At the three-month assessment, scores for all three eating behaviours had shifted. Emotional eating declined, restrained eating rose slightly and external eating decreased.

By 12 months, however, the trends had separated. Emotional eating had returned towards its starting level, as had restrained eating.

External eating, in contrast, remained lower across the full year, contrary to the direction reported in an earlier study.

Before this research, no study had clearly established which eating pattern most reliably predicts long-term success with GLP-1 medicines in routine clinical practice.

Higher external-eating scores at the beginning of treatment predicted more weight loss at 12 months.

In other words, the greater someone’s initial attraction to tempting food, the more weight they generally lost. No comparable association was found for emotional eating.

The link between brain cues and appetite

Brain imaging may offer one explanation. People with a higher body mass often display increased activity in brain regions associated with craving and reward when they view images of food.

A trial involving a related GLP-1 medicine found that this heightened activity seemed to lessen during treatment.

It remains uncertain whether the medicine causes this directly or acts through other appetite-related mechanisms.

Either way, the behavioural result was consistent. External eaters felt less drawn to tempting food, and this reduction persisted for 12 months.

Treatment may require tailoring

“GLP-1 receptor agonists are effective for individuals who experience weight gain or elevated blood glucose levels due to overeating triggered by external stimuli.” said Yabe.

“However, their effectiveness is less expected in cases where emotional eating is the primary cause,” he continued.

A separate study found that emotional eaters experienced less change in food-cue-related brain activity while receiving GLP-1 therapy, reflecting the year-long pattern reported in this paper.

When patients are asked why they overeat, their answer may therefore provide a useful clinical signal.

Limitations to consider

This observational study involved 92 people and partly depended on self-reported eating behaviour, limiting how confidently cause and effect can be determined.

All participants were from one part of Japan, and many seemed strongly motivated to improve their health.

That profile may not represent the wider population beginning these medicines.

Key clinical implications

The findings offer a clearer explanation for the uneven effects of GLP-1 medicines. External eating is the urge to eat food simply because it looks or smells attractive.

It proved to be the strongest predictor of lasting success with these treatments.

The clinical issue therefore shifts. Rather than merely deciding whether to prescribe Ozempic, clinicians may need to consider whether it should be combined with additional support.

For people who overeat because food seems irresistible, the medicine does much of the work. For those who eat because they are in emotional pain, it is only one part of a broader solution.