What happens when the medication stops

These drugs work. In the STEP 1 trial, people on semaglutide lost about 17% of their body weight over 68 weeks. But when the trial stopped the drug and followed people for another year, they regained roughly two-thirds of what they'd lost, ending about 5.6% below where they started (Ceriello et al., 2026; Shah et al., 2026).

Tirzepatide tells the same story. In SURMOUNT-4, everyone took the drug for 36 weeks and lost about 21% of their weight. Then half were switched to placebo. Over the next year the placebo group regained about 14% of their body weight, while the group that stayed on tirzepatide lost another 5.5% (Shah et al., 2026). Pooled across trials, regain after stopping runs at roughly 0.8 kg (about 1.75 lb) a month (Ceriello et al., 2026).

It isn't just the scale. Waist size, blood pressure, HbA1c, cholesterol and inflammation markers drift back toward baseline too, and in a SURMOUNT-4 follow-up analysis the reversal tracked how much weight came back (Horn et al., 2026).

I'm not sharing this to scare anyone. It's what we'd expect from an effective treatment for a chronic condition: the effect depends on the treatment continuing, the same way blood pressure medication works while you take it. Real-world data are messier (many people restart or switch drugs, so average curves look flatter), but the trial picture is consistent (Gasoyan et al., 2026).

So the honest question isn't "will exercise replace the drug?" It's "can exercise change how much of the result you keep?"

The trial that followed people for a full year after stopping

There's one study that answers that question better than any other, and it's worth knowing by name: S-LITE.

Researchers in Copenhagen took 195 adults with obesity, ages 18 to 65, without diabetes. Everyone first lost about 13 kg (29 lb) on an 8-week low-calorie diet. Then they were randomly assigned to a year of one of four things: supervised exercise, the GLP-1 drug liraglutide, both combined, or placebo (Lundgren et al., 2021).

During that maintenance year, the combination group did best, ending about 16% below their starting weight. Exercise alone prevented regain. The combination roughly doubled the drop in body fat while preserving lean mass.

Then came the part that matters for this issue. The researchers stopped all treatment and checked back one year later (Jensen et al., 2024):

• People who had taken liraglutide alone regained 6.0 kg more than people who had only exercised, even though both groups had lost similar amounts.

• The liraglutide-only group regained 6.3 kg of fat, more than 70% of the fat they'd lost.

• People who had done both were still 5.1 kg lighter than the drug-only group.

• After accounting for the drug, exercise itself was associated with about 4.6 kg less weight a year after treatment ended.

• The combination group had much higher odds than placebo of still being 10% or more below their starting weight (odds ratio 7.2).

The drug got people down. The training habit is what was still working a year after everything stopped.

Why movement helps you hold

There are three plausible reasons, and I like that they're physiological, not just "willpower."

Your own GLP-1. In an S-LITE follow-up analysis, a year of exercise raised the body's own after-meal GLP-1 response by 37%, about 25% more than usual activity. The drug groups showed no change in their natural GLP-1 (Holt et al., 2025). In other words, training appears to rebuild some of the appetite signaling the medication was providing.

Appetite signals. Exercise modestly lowers ghrelin, the hunger hormone, and reduces hunger ratings and relative food intake. The effects are real but small, so this is a nudge, not a switch (Li et al., 2025; Quist et al., 2019).

Muscle and metabolism. Between a quarter and about 40% of the weight lost on GLP-1 drugs can be lean mass, and when people regain, it comes back mostly as fat (Lieberman et al., 2026). Resistance training can cut diet-related lean-mass loss by roughly 50–95% (Locatelli et al., 2024), which helps protect resting metabolism. Exercise plus the drug also preserved bone density in S-LITE, where the drug alone reduced it (Jensen et al., JAMA Netw Open, 2024).

The fine print

I want to be straight with you about how strong this evidence is.

Exercise slowed regain. It didn't stop it. The effect in S-LITE is meaningful but partial.

It's essentially one trial, and it used liraglutide. That's an older, less potent drug than semaglutide or tirzepatide. No randomized trial has yet tested exercise after stopping the newer agents, and that's the biggest gap in this research (Jensen et al., 2024; Mehrtash et al., 2025).

It wasn't a 40+ study. S-LITE enrolled adults 18 to 65. Almost none of the GLP-1 discontinuation research is specific to our age group, so I'm extrapolating, carefully.

The volume targets are softer than they sound. You'll often see 200–300 minutes a week of moderate activity recommended for weight maintenance. That number comes mostly from observational data, and randomized trials haven't consistently shown it beats 150 minutes (Jakicic et al., 2024; Swift et al., 2026).

And the three myths worth retiring:

• "Exercise can't prevent regain once you stop." Too absolute. It measurably reduced regain in the best trial we have.

• "Exercise doesn't help weight loss, so it won't help maintenance." Exercise alone produces modest loss, which is where this myth comes from. Its real value shows up in maintenance, muscle, bone and heart health.

• "Once you start, you're on it forever." Partly true. Many people will regain without ongoing therapy, and that's a decision for you and your prescriber. But lifestyle, especially exercise, can preserve a meaningful share of the benefit, and lower-dose and step-down strategies are being studied.

The good news: the best time to start is now

If you're on a GLP-1 right now, you're in the best window you'll get. Lower appetite makes it easier to add training, recover from it and build muscle before hunger returns. That's the clearest practical lesson from S-LITE: the people who trained during treatment carried the benefit into the year after (Jensen et al., 2024). No trial has compared starting during treatment with starting at taper, so this is a reasoned inference, not proof.

And even if some weight comes back, the gains in fitness, strength, blood pressure and insulin sensitivity often hold (Swift et al., 2026; Jensen et al., Sports Med, 2026). Count those as wins.

What this looks like in a real week

General guidance for an apparently healthy adult, drawn from ACSM, AHA and a JAMA Internal Medicine framework (Jakicic et al., 2024; Swift et al., 2026; Mehrtash et al., 2025):

• Move: Build to 150 minutes a week of moderate activity (or 75 vigorous). Once that's steady, work toward 200–300 if you need more. S-LITE used about four sessions a week: two harder (30 minutes of vigorous cycling plus a 15-minute circuit) and two easier walks, runs or rides.

• Lift: Two to three full-body sessions a week, about 60–90 minutes total. Machines and bands are a fine start.

• Walk more: Add daily steps on top of workouts. Light activity counts.

• Plan the handoff: Start now, not when your prescriber talks about tapering, and keep your care team in the loop.

For adults 40+, I'd add: progress slower than you think you need to, leave a day between hard lifting sessions, and lean on joint-friendly options like cycling, water work or machines when something's cranky.

Where my job ends

Here's where I draw the line, because it matters with these medications.

Programming exercise for an apparently healthy adult (cardio, lifting, mobility, balance) and sharing general public-health nutrition guidance is squarely in my lane as an ACE-certified trainer. Deciding whether to start, stop, taper or re-dose a medication is not. Neither is managing side effects, adjusting insulin or sulfonylureas (which can raise low-blood-sugar risk when you add new activity), or individualized nutrition plans. Those belong to your prescribing physician and a registered dietitian.

Stop and contact your physician if you notice chest pain or pressure, unusual shortness of breath, fainting or near-fainting, a racing or irregular heartbeat, persistent dizziness, signs of low blood sugar (shakiness, sweating, confusion), signs of dehydration, or severe or persistent abdominal pain. If you're currently inactive and planning vigorous exercise, or you have heart, metabolic or kidney disease, get medical clearance first (Riebe et al., 2015).

The takeaway

The medication can take the weight off. The habit you build while you're on it is what helps you keep it.

What I can't do in a newsletter is look at your medication timeline, your week and your training history and tell you what to do with it. That's the part that needs a person, and it's the part I love doing.

Drop HOLD in the comments on this week's post for the full breakdown, or if you're ready to build your plan, book a free 15-minute assessment call (link in bio).

Richard Skolasky is an ACE Certified Personal Trainer. This article is for general educational purposes only and does not constitute individualized exercise prescription. Consult a qualified healthcare provider before beginning or modifying a training program.

REFERENCES

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2. Gasoyan H, Schulte R, Boyer CB, et al. Obesity treatments and weight changes in clinical practice after discontinuation of semaglutide or tirzepatide. Diabetes Obes Metab. 2026;28(6):4795-4805. doi:10.1111/dom.70660

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9. Li N, Wu M, Li Y. Acute exercise effects on appetite and energy intake in people living with overweight and obesity: a systematic review and meta-analysis. Int J Sport Nutr Exerc Metab. 2025:1-17. doi:10.1123/ijsnem.2025-0078

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