Ozempic, Wegovy, and Data

I’ve gotten a lot of questions about Ozempic and Wegovy and, more broadly, about the class of drugs to which they belong. Some of the questions overlap with parenting, given the recent American Academy of Pediatrics guidance suggesting the possibility of medical treatment for obesity for children 12 and up. Some of the questions overlap with questions about diet, a topic about which I’ve written both here and in my academic research. I am going to do my best to answer many of these today and frame (at least from my perspective) why this makes so many people hopeful, so many others angry, and many very confused. What are Ozempic and Wegovy? Ozempic and Wegovy are both part of the same drug class — they are injectable semaglutide. Ozempic is approved to treat Type 2 diabetes, and Wegovy is approved to treat obesity. Both, however, work through the same mechanism and both have effects on weight. The mechanism here is that the drugs mimic a hormone called GLP-1 that targets appetite. People feel less hungry and they eat less. This causes weight loss. It also impacts Type 2 diabetes and other cardiovascular complications, probably due in part to the impacts on weight. What do we know about their effectiveness? When talking about effectiveness, it’s important to start with what we know about the effectiveness of the baseline alternative, which is diet and exercise. These approaches are generally not shown to be very effective for sustained weight loss among people struggling with obesity. It is extremely difficult to get people to change their diet and exercise behavior in the long term. I’ve written about this in the context of diabetes, using grocery scanner data to show limited changes in diet after a diabetes diagnosis. We know from a huge body of literature that changes to diet have largely short-term impacts on weight. This doesn’t mean people cannot lose weight through better eating and physical activity. They can, and some people can keep it off in an ongoing way. But it is not the norm. Relative to the studies we have of diet, the impacts of these drugs on weight are substantial. The largest trial of Wegovy was published in the New England Journal of Medicine in 2021. This is in our highest evidence standard: a double-blind, placebo-controlled study, meaning that there was a treatment and a control group and neither the participants nor their doctors knew which group they were in. Of the 1,961 adults enrolled, all of them had a BMI of greater than 30 (or greater than 27 with a weight-related comorbidity) and did not have diabetes. Follow-up here was extensive — 68 weeks. From baseline to week 68, the treatment group lost an average of 14.9% of their body weight (15.3 kilograms), versus 2.4% for the placebo group (2.6 kg). About two thirds of the weight loss was in the first 20 weeks (see graph below). The treatment group also improved on other measures of health. It is this result that has promoted the excitement we see in at least some corners of this discussion. This is a sizable weight loss, and it appears sustained through a relatively long period of time. This effect has been echoed in other studies; you’ll see variation in the exact numbers, but these drugs are effective for weight loss over the time frame seen in these studies, for study participants. What do we know about side effects? The main way we look for side effects is in the trial data. In that same NEJM paper with the main results, the authors look for adverse events. Seven percent of the treatment group experienced an adverse event severe enough to discontinue treatment, versus 3.1% of the placebo group. The most common adverse event of any severity was gastrointestinal issues. These are much more common in the treatment group — 74% of that group reported some combination of nausea, diarrhea, and vomiting, versus 47.9% of the control group. Although rarer, the treatment group was also significantly more likely to have hepatobiliary disorders (affecting the bile ducts, pancreas, and gallbladder) — 2.5% versus 0.8%. There are other warnings on these medications, the scariest of which is probably the concern about thyroid cancer. In mice and rats, these drugs were linked with this cancer; it’s difficult to know whether that will translate to people, although generally they aren’t recommended if you have a family history of thyroid cancer. An important caveat, related to the next question, is that if there were longer-term side effects, we wouldn’t know about them yet. Similarly, if there are rare side effects, we will not pick them up in the data until there are more people taking these medications. After-market monitoring by the FDA (similar to what is done with vaccines) may reveal these. Do you need to take these drugs forever? This is sort of the million-dollar question. These drugs feel different when imagining one takes them for only a year than if this is a lifetime sign-up for a weekly or biweekly injectable plus some degree of nausea. We do not have complete data on this yet, although what we have does suggest a need for continuation. The graph below summarizes what happened in the drug trial after week 68. Most of the weight was regained, and pretty quickly. The regain effects are a little subtle. A trial published in JAMA also in 2021 evaluated this question by starting a full cohort of people on medication and then taking a third of them off it at 20 weeks but leaving them on a placebo. In this case, the group regained about half of what was lost. It’s less extreme than the effect above, suggesting the continuation of some placebo impact. Overall, though, the data here suggests that sustained weight loss requires sustained treatment, at least at some dosage. What do we know about these medications in children and adolescents? Wegovy is approved in children over 12, based on a combination of the evidence in adults and this trial in teens. The trial included 201 children ages 12 to 18 with diagnosed obesity. Treatment decreased BMI by an average of 16.1% in the treatment group, with basically no change in the placebo group. Similar to the trials in adults, gastrointestinal issues were common in this group (62% of treatment, 42% of placebo). There are many things we do not know, including weight regain if the medication is ceased. Can you take Ozempic and Wegovy during pregnancy? No. Based on evidence in mice, there are concerns about a higher risk of miscarriage and birth defects. These drugs should be discontinued during pregnancy. Over time, we’ll learn more about this based on accidental pregnancy exposures, but for now it should be avoided. Why are feelings running so high? Let me start by noting that this is my opinion. It’s always hard to tell why people are happy or angry, so really all we can do is speculate. It is easy to see why there are people cheering for this. Many people are interested in losing weight for health reasons; although the links between weight and health are far more complex than is generally recognized, there are medical conditions to which a higher weight is a contributing factor. The impact of Ozempic on diabetes is clear, and Type 2 diabetes has significant health impacts. This is the first class of drugs with clear evidence of large impacts on weight and health metrics. So that is exciting. On the other side, I see at least three big narratives of concern. First: Ozempic in particular is approved for use in diabetic patients, where it can have large positive health impacts. In a number of cases, people who want to lose weight for non-medical reasons have sought out this drug, generating shortages. This is extremely problematic. Second: The evidence on long-run impacts suggests it is an indefinite prescription. That’s uncomfortable for many people. It’s not dissimilar to existing medications for chronic conditions (e.g. metformin for diabetes), but the concept of a weekly injectable for life seems to feel different for many. Especially one that generates a feeling of mild nausea much of the time. Third: This is new. Despite the several years of follow-up in these trials, we do not yet have the data to answer many of the questions we might have about possible rare side effects, or any implications of long-term use. There is no solution to this; it’s just the reality of new medications. Finally: My sense is there is some discomfort with the idea of these medications and how they interact with the significant amount of weight stigma that our society harbors. If there is a medication that can help people lose weight, is that going to increase weight bias? This is a problem well outside the medical question of these drugs. Bottom line: These discussions are ongoing. Hopefully the evidence here helps in understanding the underlying data better.

Ozempic, Wegovy, and Data

What we know—and what we don't

This Post Is for Paid Readers Only