What Happens When You Stop Weight-Loss Medication?

What a Major Study Found (and What It Means for Your Next Step)

Most people don’t stop treatment because they “gave up.”

They stop because life gets busy, routines slip, the scales plateau, side effects appear, finances change, or they simply feel they’ve “done enough” and want to see if they can maintain progress without medication.

That’s a completely understandable thought. And it’s exactly why a recent analysis published in JAMA Internal Medicine (Nov 2025) is worth talking about—because it helps answer a question many patients quietly carry:

“If I stop now, will the progress stay?”

The short answer: for most people, weight regain is common- and it often comes with loss of health improvements too, unfortuantely

The analysis looked at adults with obesity who had already achieved meaningful weight loss on tirzepatide (it's the scientific name of Mounjaro pen) during a structured treatment period. Then, treatment was stopped (withdrawn) and participants were followed for a year.

What happened next was striking.

Within only 1 year after stopping treatment:

82.5% of participants regained at least 25% of the weight they had lost.

That doesn’t mean everyone returned to square one—but it does mean that for most people, the body pushed back.

And the pattern didn’t stop there:

About 1 in 2 participants regained 50% or more of their weight loss
About 1 in 4 regained 75% or more
And almost 9% regained more than 100% of the weight they had lost (i.e., ended up above their post-loss starting point)

This is one of the clearest clinical reminders that obesity behaves like a chronic, relapsing disease, not a short-term project you “finish.”

It wasn’t just weight. Health markers also moved in the wrong direction

Weight loss is often discussed in terms of clothing size or confidence—and those are real and important outcomes. But clinically, the bigger story is often what happens under the surface: blood pressure, waist circumference, lipids, glucose control, insulin resistance.

In this analysis, the degree of weight regain was linked to a reversal of cardiometabolic improvements.

Here are some of the most practical, patient-relevant changes seen after stopping treatment:

Waist circumference (central fat)

As weight regain increased, so did waist size. Over the year after withdrawal, average waist circumference increased by:

~0.8 cm in those with minimal regain
~5.4 cm with moderate regain
~10.1 cm with larger regain
Up to ~14.7 cm in those with the highest regain

Waist circumference matters because it’s a rough marker of visceral fat, which is strongly linked to cardiometabolic risk.

Blood pressure

Systolic blood pressure increased across categories after stopping treatment, rising by:

Up to ~10.4 mmHg in the highest regain group

Even modest increases in blood pressure can matter over time—especially if someone already has elevated baseline risk.

Blood sugar markers

Markers of glycaemic control worsened in step with weight regain:

HbA1c increased by up to ~0.35% after withdrawal (highest regain group)
Fasting glucose also rose (up to ~9 mg/dL in higher regain categories)

For patients with insulin resistance, prediabetes, or a strong family history of type 2 diabetes, this is clinically meaningful.

Cholesterol and insulin resistance

Unfavourable lipid changes and insulin resistance also returned:

“Bad” cholesterol (non-HDL) rose by up to ~10.8%
Fasting insulin increased substantially in higher regain groups (for example ~46% in one category)
Insulin resistance indices also worsened most in those who regained more

The overall takeaway from the paper was consistent:
the more weight that returned, the more cardiometabolic benefit was lost!

“Does this mean I’ll regain weight if I stop?” Not necessarily- but it’s a risk you should plan for

One of the most helpful parts of the analysis is that it shows variation. Not everyone regained the same amount. A smaller group—about 17.5%—kept weight regain below 25%. Some even continued losing weight after withdrawal.

So what’s the point of sharing the “big” numbers?

Not to scare you. And not to imply medication is the only tool.

The point is to be honest about what many people experience, so you can make a plan that’s realistic—especially if you’ve previously had cycles of losing and regaining weight.

Because when weight regain is framed as a personal failure, people tend to disappear and avoid support. When it’s framed as biology and disease physiology, people are far more likely to seek the right help early.

Why does weight tend to come back?

This is the part many patients don’t get told clearly enough.

After significant weight loss, the body often responds with:

increased hunger signalling
reduced satiety
a tendency to conserve energy
behavioural and hormonal changes that push weight upward

That’s not a moral issue. It’s physiology.

It’s also why most evidence-based obesity guidelines treat pharmacotherapy as something that may need to be continued long-term, just like we treat blood pressure or cholesterol.

What you can do if you’ve stopped (or you’re thinking about stopping)

If you’ve paused treatment, the most important step is not to judge yourself—it’s to decide what support you want next.

Here are sensible next moves:

Don’t wait for a “complete reset.”
If weight regain has started, addressing it early is usually easier than trying to reverse a full rebound.
Review your treatment plan rather than stopping abruptly without a strategy.
Some people may benefit from a maintenance approach, dose adjustments, or a planned transition.
Track more than the scale.
Waist circumference, blood pressure, and glucose markers matter—sometimes before the scale changes dramatically.
If side effects or cost were the issue, say so.
Those are common reasons people stop. A review can often find a safer or more sustainable approach.

How Rightangled can help?

If you’ve previously been on treatment through our service and stopped ordering, you don’t need to “start from scratch” alone.

Our clinicians and prescribers can help you:

review your current situation and goals
consider whether ongoing treatment is appropriate for you
discuss side effects and risk factors
build a realistic maintenance plan

If you want to restart, the key is doing it safely and appropriately, with a plan you can actually sustain.

Ready to review your next step?
Start here!

References

Horn DB, Linetzky B, Davies MJ, et al. Cardiometabolic Parameter Change by Weight Regain on Tirzepatide Withdrawal in Adults With Obesity: A Post Hoc Analysis of the SURMOUNT-4 Trial. JAMA Internal Medicine. Published online Nov 24, 2025. doi:10.1001/jamainternmed.2025.6112