Do GLP-1 weight loss drugs stop working long-term?

What did @thetodayshow actually say?

The Today Show's segment made three connected claims: stopping weight loss injections causes people to regain lost weight in under two years, that regain happens faster than with any other weight loss plan, and that risk markers for diabetes and heart disease can return after stopping.

To their credit, the framing is mostly grounded in real research. The STEP 1 trial extension (Wilding et al., 2022, New England Journal of Medicine) tracked semaglutide users who stopped after 68 weeks and found participants regained about two-thirds of their lost weight within one year of stopping. That's a real finding from a rigorous trial. The cardiovascular and metabolic marker rebound is also documented. So the segment isn't fabricated. But the way they stitched it together created a misleading picture, and one specific claim, the "faster than any other weight loss plan" line, is not supported by the evidence they appear to be referencing.

Does the science back this up?

Partly, yes. The weight regain data is solid, but the comparative claim about speed of regain is a stretch that the studies don't actually make.

Wilding et al. (2022) is the most-cited study here. After semaglutide was discontinued, participants regained roughly 11.6 of the 17.3 kg they had lost, within 12 months. That's significant. A similar pattern was documented with tirzepatide in the SURMOUNT-4 trial (Aronne et al., 2024, JAMA). Participants who switched from tirzepatide to placebo regained 14% of their body weight over 52 weeks, while those who continued lost another 5.5%.

But here's what the segment glossed over: these studies weren't designed to compare regain speed against other interventions like calorie restriction, surgery, or behavioral programs. The "faster than any other weight loss plan" claim implies a head-to-head comparison that doesn't exist in the literature the segment appears to draw from. That's a meaningful overreach.

What did they get wrong (or right)?

They got the core biology right and the comparative framing wrong.

The claim that "risk markers for diabetes and heart disease can also return" is accurate. Wilding et al. (2022) showed that cardiometabolic improvements, including blood pressure, blood glucose, and lipid levels, largely reversed after stopping semaglutide. This is consistent with how GLP-1 receptor agonists work: they suppress appetite and improve insulin sensitivity while active, but those effects are not permanent once the drug is cleared.

Where the segment earns criticism is the phrase "faster than those on any other weight loss plan." That's a comparative claim requiring comparative data. No major published study has run a controlled race between post-GLP-1 regain and post-diet regain speed. Some research, like Wadden et al. (2020, Obesity), suggests behavioral interventions produce slower initial loss and often slower regain, but that's not a clean comparison either.

The framing also implies these drugs are uniquely problematic, when in fact weight regain after stopping any obesity treatment, including bariatric surgery in some cases, is a documented phenomenon across the board.

What should you actually know?

Weight regain after stopping GLP-1 medications is real, well-documented, and clinically important. But the takeaway from that fact is more nuanced than "these drugs don't work."

The STEP 1 extension and SURMOUNT-4 data suggest these medications may need to be taken long-term to maintain their effects, similar to how antihypertensives or statins work. You don't stop a blood pressure drug and expect your blood pressure to stay low. The same logic applies here. That's not a flaw unique to GLP-1 drugs. That's how most pharmacological treatments for chronic conditions function.

The segment's framing, "turns out weight loss drugs might not be the way to go," risks pushing people away from a class of medications that have demonstrated meaningful cardiovascular benefit in trials like SELECT (Lincoff et al., 2023, NEJM), which showed semaglutide reduced major cardiac events by 20% in people with obesity and established cardiovascular disease, regardless of weight loss achieved.

• Weight regain after stopping is real and backed by multiple large trials.
• The "faster than any other plan" comparison is not supported by head-to-head data.
• Cardiometabolic markers do tend to rebound, but this is consistent across most obesity treatments.
• Long-term use may be necessary for sustained effect, similar to other chronic disease medications.
• Framing these drugs as ineffective ignores their documented cardiovascular benefits.