Mounjaro and Wegovy: What Happens If Tolerance Develops? Changes After Stopping and How to Manage It

GLP-1 class weight-loss injections,

Mounjaro and Wegovy,

are medications that help with

weight loss effects and

blood sugar control,

and interest has recently surged in Korea as well.

However, when used for a long period,

questions such as “Will tolerance develop?”

and “Will weight rebound if I stop taking it?”

inevitably come up.

Today, I’ll organize these two questions

with a focus on those points.

Tolerance refers to

a phenomenon in which

even when the same dose of a medication is used,

the effect decreases over time.

However, what is commonly called “tolerance”

with Mounjaro and Wegovy

is, medically speaking, often not actual tolerance,

but rather

“a slowing of the rate of weight loss” or

“the maintenance phase after weight reduction.”

📌 In multiple long-term clinical trials,

both Mounjaro and Wegovy

showed weight loss at the beginning of use,

but after a certain point,

no further weight reduction occurred,

and a “plateau phenomenon” was observed.

This is simply a plateau reached at the limit of the drug’s effect,

and it is difficult to view it as “tolerance,”

in which the drug response itself disappears.

👉 Put simply,

when weight loss stops while using Mounjaro or Wegovy,

it falls under the “plateau phenomenon,”

and it cannot really be described as tolerance.

https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2022/08/04/15/32/SURMOUNT-1

https://www.nature.com/articles/s41591-024-02996-7

https://www.nature.com/articles/s41591-022-02026-4

: With both medications, stopping them tends to lead to appetite recovery and weight regain,

but there are differences in the details.

(1) Mounjaro

GIP

(Glucose-dependent Insulinotropic Polypeptide) is

a hormone that promotes insulin secretion,

and Mounjaro activates this GIP receptor

along with GLP-1.

The action of GIP is known to play a role not only in

appetite suppression,

but also in promoting

energy expenditure (calorie burning)

within the body.

Therefore, after stopping Mounjaro,

GLP-1 activity may decrease,

and appetite may increase again,

but thanks to the action of GIP, energy expenditure in the body is

affected to some extent,

so the rate at which weight is regained

may be relatively slower than with Wegovy.

(2) Wegovy

Wegovy is

a GLP-1 receptor agonist,

and this medication

mainly reduces food intake and keeps you feeling full for longer

by suppressing appetite and delaying gastric emptying.

Therefore, when the medication is stopped,

the appetite-suppressing effect quickly weakens,

leading to a return to eating more food than usual,

so relatively rapid weight regain

is more likely to occur.

Mounjaro and Wegovy

are effective for weight loss,

but if the medication is stopped for a short period or if management is lacking,

rebound weight gain can appear strongly.

Therefore, it is important to always adjust the medication gradually

under the guidance of medical professionals

and maintain the improved lifestyle habits.