Why weight returns fast after stopping obesity drugs? Homeostasis explained

Here's how homeostasis, hormones and obesity drugs affect why lost weight often returns faster than expected

For many people, weight loss is followed by rapid regain, particularly after obesity drugs are discontinued. This pattern is now well documented in medical research, including the recent study published in The BMJ, and is driven by the body’s natural weight-regulating systems.

 

“This is not a failure of willpower,” says Dr Jatin Kumar Majhi, Associate Consultant – Endocrinology at Manipal Hospital, Bhubaneswar. “It is the body’s homeostatic system doing exactly what it evolved to do, which is protect long-term survival.”

What is homeostasis, and why does it affect weight loss?

Homeostasis is the body’s internal balancing system. It keeps vital parameters like blood sugar, temperature, and blood pressure within a narrow, safe range. According to Dr Majhi, body weight is defended in much the same way.

 

 

“The body maintains a constant body weight through a complex homeostatic system that senses energy intake and expenditure,” he explains. “Signals from the brain, gut, fat tissue, pancreas and adrenal glands all communicate continuously to preserve survival.”

 

From an evolutionary perspective, fast weight loss isn’t a goal; it’s a warning sign, a danger that something unusual is happening in the body.

Why does rapid weight loss trigger homeostasis?

“When people lose weight rapidly, the body interprets it as a threat,” says Dr Majhi. “It mounts a vigorous biological defence to restore the previous weight.”

 

According to him, the body pushes hard to bring it back, much like it would correct falling blood sugar or dropping body temperature, for survival.

Which hormones are responsible for pulling the weight back on?

Several powerful hormones shift the moment weight is lost. “As fat mass reduces, leptin production from fat cells decreases,” Dr Majhi explains. “Lower leptin promotes food-seeking behaviour and reduces energy expenditure.”

 

At the same time, ghrelin, which is the hormone that stimulates appetite, rises. Hunger increases, satiety weakens, and cravings sharpen.

 

Insulin sensitivity may initially improve, but adaptive signalling can later favour fat storage. Stress hormones also join the conversation, nudging the body into an energy-conservation mode.

 

“All these signals function together to encourage weight regain,” Dr Majhi says.

So how do obesity drugs manage to override this system temporarily?

Obesity medications work by modifying appetite and satiety signals.

 

“These drugs alter the body’s regulatory cues related to hunger and fullness,” explains Dr Majhi. “As a result, people can lose weight with far less perceived hunger.”

 

The keyword here is perceived. The underlying homeostatic system hasn’t disappeared, it’s been muted.

Do obesity drugs permanently reset the body’s weight set point?

“Current research shows that these medications do not permanently change the body’s weight set point,” says Dr Majhi. “That’s why continued medication is often required.”

 

Once the drug is stopped, the suppressed hunger hormones rebound. But calorie expenditure remains low from prior weight loss.

 

“This creates the perfect environment for rapid regain of fat mass,” he explains, “sometimes even exceeding the original starting weight.”

 

This is why weight regain feels faster after stopping drugs than after lifestyle changes. With drug-induced weight loss, especially without resistance training, lean muscle may be lost alongside fat. Less muscle means a slower metabolism, making regain faster and more efficient.

 

“Regular exercise helps preserve lean muscle mass and supports a healthier metabolism,” says Dr Majhi. “This can slow the rate of weight regain.”  For more health updates, follow #HealthWithBS 

This content is for informational purposes only and is not a substitute for professional medical advice.