The science behind the Ozempic craze — and what's next

haven’t used this many footnotes in a minute

Sophia Wronsky

Feb 26, 2025

- More deep dives into F&B and healthcare (like this one)

- An interview with a food reality TV star

- The cure for the sad desk lunch

- Good stuff to eat and Irish zaddies to ogle

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Dear reader,

You’ve probably been aware of the concept of calories in/calories out (CICO) since the first time you looked at yourself naked and thought “oof.”

The concept that you can lose weight simply by reducing your caloric intake (or burning more calories through exercise) is embedded at the foundation of the weight loss industry. I spent years working at and advising companies in this industry, and found it extremely frustrating that CICO has maintained such a chokehold on public discourse. While it is true that consuming fewer calories for a period of time will likely result in short-term cosmetic weight loss (e.g., my break-up diet of 2013 during which I only ate one ham and cheese croissant a day and lost 10 lbs), it is not the full story for sustained, significant weight loss. Research shows that achieving sustained, significant weight loss (10%+ of body weight for 12+ months) is virtually impossible on a calorie-restricted diet alone.12 CICO is, however, a simple, mathematical formula that is easy to grok, and no one has come up with a succinct alternative or explained why doesn’t work.3 I took a stab, below, and will be spending some time brainstorming alternatives.

Why CICO Doesn’t Really Work (it’s complicated, it’s personal)

Not all calories are created equal: your body extracts different amounts of energy depending on the macronutrients in the food (e.g., carbohydrates, fats, proteins).
You have a “set point”: your body speeds up or slows your metabolism to respond to the differences in caloric intake to keep the body the same weight or fat mass.4
The bugs in your gut have an opinion: your microbiome influences how many calories are absorbed.5
You can’t “burn off” a big meal on the treadmill: your body will respond to increased exercise by reducing the energy it expends on other activities (e.g., resting metabolism, fertility)

Other Important Notes:

There are even more factors in play: hormones (e.g., leptin, ghrelin, and insulin) play a role in appetite, satiety, and fat storage; sleep, stress, and exercise all contribute.
Many foods, particularly those that are low in fiber (e.g., potato chips, white bread), decrease satiety (the fancy word for “I’m full”), which can result in people eating more.
Shakes, bars, and other meal replacements often lack fiber and other nutrients. So while you might hit your macros, you may miss your micros and/or experience a host of unpleasant GI issues.

Ahead of the USDA releasing new dietary guidelines later this year, the most simple and repeatable guidance for weight loss I’ve been able to find remains: “Eat food. Not too much. Mostly plants.” (Michael Pollan)

GLP-1s

The tl;dr: while it seems like everyone in Hollywood and on TikTok are taking GLP-1s to lose weight, they will likely not sustain results unless they make behavioral changes in tandem.

GLP-1 agonists (e.g., Ozempic, Wegovy) are a class of medications that mimic a naturally occurring hormone that regulates blood sugar, promotes satiety, and reduces inflammation, leading to weight loss with relatively few side effects. Originally used for the treatment of diabetes, they have proven to be extremely effective at weight loss for people with obesity in clinical trials (notably, they have not been tested on those of “normal weight”). Critically, these medications have not been proven to drive sustained weight loss results: those who stop medications typically regain nearly all of the weight.6

Some companies (including my former employer, Calibrate, and legacy players like WeightWatchers), are attempting to prove that a combined regimen of medications and intensive lifestyle intervention can drive sustained weight loss and change the metabolic set-point. They have had promising preliminary results (over 90% maintained at least 10% weight loss after stopping GLP-1s).7

Access to GLP-1s is getting easier and the vanity marketing machine is working its magic, so companies offering a combined approach will continue to struggle to achieve scale and adoption when the market is flooded with easy alternatives:

Industry Outlook

With increasing rates of obesity in the US (>70% adults have obesity or overweight), it’s no surprise that the weight loss industry is massive (>$100B for GLP-1s alone) and continues to grow. A few companies that I have my eye on:

ZOE: As I noted above, genetics and microbiome have an impact on metabolic rate, and ZOE is offering a personalized nutrition program. I’m impressed by the founding team, evidence-based trials, and integration of home-based tests. I’m bummed that they aren’t available in NY yet — although the requirement of state-by-state approvals is a great example of why innovation in digital health in the US is hard.
Function Health: is buzzy for its celebrity endorsements and recent injection of cash — which I’m sure is subsidizing the cost of the battery of testing ($15,000 per person) that gives customers a view into their health. I’m interested if 1) what nutritional advice Function will prescribe, 2) what Function is going to do with all that data long-term, and 3) what my biological age is.
Compounding Pharmacies (e.g., hims & hers): given supply shortages in GLP-1s from pharmaceutical companies, the FDA allowed pharmacies to compound and sell medications on the cheap. Now, the supply chain challenges have been resolved, and big pharma is sounding the alarm that compounded medications are not safe. Expect lots of noise, lawsuits, and ads about this.

The companies I noted above are getting really good at testing and marketing — but it’s unclear which will be able to deliver sustained outcomes. There are a number of opportunities for the taking:

Optimized content and products for GLP-1 users to sustain outcomes
Personalized nutrition coaching — that actually teaches you how to cook
Early diagnosis and intervention for disease prevention in what defines as the pre-chronic market

Other Stuff & Things

Wishing they’d make a movie about a rat sommelier after learning that rats can distinguish between varietals of wine.
Delighted that the prime minister of Denmark is really into baby carrots. Same, girl, same.
Continuing to be alarmed by what is happening at the FDA, especially in the wake of the rise of food safety recalls in 2024. Should we start giving pro-science wellness creators $$?
Adding “how to add the ultra-processed food pipeline” to my ever-growing list of fears about raising a child.
Loving The Cut’s coverage of what the chefboiz are cooking (and wearing) for date night.
Obsessing over Veuve Clicquot's marketing partnerships. First the SMEG fridge, now Moon Boots (spotted at a consignment store in Sun Valley this weekend)? Be still my heart.