Obesity Medications Don’t Explain Decrease in Obesity Rates — At Least Not Yet

I keep seeing stories purporting that the reason the United States has seen a tiny decrease in obesity rates since 2020 is our recent generations of obesity medications. I am a huge proponent of these medications and I think they absolutely will affect rates of obesity, but I don’t think this drop is a causal consequence of their prescription. Let’s explore why.

First, we can scratch off the impact of the first generation of glucagon-like peptide-1 (GLP-1) analogs, liraglutide. Marketed as Saxenda, it was approved for obesity in 2014. While somewhat helpful, average losses seen in patients taking it — at 56 weeks, 12 more pounds than those taking placebo — were clearly insufficient to bend the obesity rate curve. This may reflect several factors, including lack of coverage leading to few prescriptions, poor patient adherence consequent to side effects or daily injection requirements, or simply to lack of enthusiasm around its prescription or continuation, given the small amount of ascribed weight loss.

Next is the timing when considering second- and third-generation GLP-1 analogs, semaglutide (Wegovy) and the dual glucose-dependent insulinotropic peptide (GIP)/GLP-1 tirzepatide (Zepbound). Centers for Disease Control and Prevention (CDC) data show that obesity rates began declining in the spring of 2020 (more on that later). Yet, the second-generation GLP-1 analog Wegovy wasn’t approved by the US Food and Drug Administration (FDA) for managing obesity until June 2021, while the third-generation drug Zepbound only received approval for obesity in November 2023. 

While it’s true that these drugs were being used off label prior to their formal FDA approval for obesity, they were not being prescribed as readily as they are today. And even today, their cost and lack of insurance coverage markedly limit their use and impact. 

Also limiting their use were nationwide shortages, first of Wegovy and then of Zepbound, between 2022 and late 2024, which no doubt had an impact on new prescriptions of these medications, as well as on their continued use even among patients who had experienced benefits and minimal side effects. 

Then there’s the issue of the discontinuation of these drugs. One study reported that 50% of those prescribed these medications for obesity discontinued them within 12 months (with 30% discontinuing them within 3 months). And just as with any medication for any chronic medical condition, if treatment is stopped, the condition returns. 

These drugs need to be started at very low doses, with dose increases recommended to occur no more frequently than once monthly to reduce the risk for side effects. Reaching a usefully therapeutic dose for most patients requires 3 months of titration, and more time is required after that to accumulate significant losses. So, even if not discontinued, these drugs aren’t likely to have marked impacts on weight for 3-6 months following their prescriptions. And a reminder again that Wegovy was approved only in June 2021 and Zepbound in November 2023, but obesity rates appeared to decrease starting in the spring of 2020.

What else was happening in the spring of 2020 that might have affected obesity rates if these drugs couldn’t? Out-of-control, prevaccination COVID, where we know that people with obesity have a disproportionate risk of dying from COVID and where disproportionate deaths among people with vs without obesity would be expected to affect obesity rates overall. Also likely to be impactful are disproportionate hospital admissions and severe disease courses for patients with obesity, with the CDC reporting obesity leading to a tripling of risk for admission due to COVID. This matters because lengthy hospitalizations, ICU stays, and increased overall disease severity would all probably lead to very significant weight losses. An attempt was made to partially quantify this, which revealed that among a cohort of patients with obesity, a COVID-related ICU admission led 69% to a > 5% weight loss and 31% to > 10% weight loss.

As to the future, however, if availability and coverage for obesity medications increase, there’s zero doubt that they would have a dramatic impact on obesity rates. For instance tirzepatide’s SURMOUNT-4 trial revealed an average weight loss of a staggering 25.3% at 88 weeks. 

To sum up, yes, we are entering an era where therapeutic full remission of obesity is a real possibility, but where our enthusiasm for medications already having had an impact is premature and where the truth is probably tragic.