The future of weight loss is data, not pharma

In my Substack piece I attacked the corruption and greed which lies behind Big Pharma's recent push to medicalize obesity, but I wanted to extend that essay here, to look at the history of weight loss treatments, and ask: what are the alternatives?

The run-up to Big Pharma’s development of GLP-1 meds like Wegovy, or Ozempic used off-label is long and complicated, but the bottom line is: other ways to lose weight have worked very poorly, or not at all. It's the failure of these other approaches that opened the door for pharma to sweep in and spend billions on marketing in exchange for tens of billions in sales.

I’d like to sketch out the history of the weight loss industry, and point to what’s coming next. I propose a timeline like this:

1. The “before” era — before the last century, the concept did not really exist. The percentage of people in the early 1900s and before who were obese was very low. Starvation was a much bigger risk than obesity.
2. Faith-based — I use the term very loosely to mean “faith-based” mechanisms that were not scientific or empirical, just commandments that “thou shalt do this” or “thou shalt do that” and then magically, weight loss would follow
3. Scientific-theoretical — attempts to generalize from scientific principles like “calories” or “keto” to make them useful and actionable to an individual.
4. Pharmacological — injectable hormone interventions to “force” the body into a metabolic shift, with weight loss as a consequence
5. Data-driven technological (or scientific-empirical) — a data-driven approach that creates metabolic shift via real-time data, with “nudges” to change behavior

1) The “before” era

All of history, to the late 1800s

For most of human history, the idea of weight loss and dieting on purpose did not make sense. I read Anna Karenina recently, set in 1874, and it was striking when they talked about children that their overwhelming concern was for them to grow as much as possible, as quickly as possible. The biggest risk then (and all of human history, in fact) for both children and mothers was the threat of disease or starvation. Obesity was very rare, and not in the shortlist of major concerns. For almost the entire population, weight loss was a very negative or alien concept, associated with disease like cholera or tuberculosis.

2) Faith-based

Late 1800s to 1920s

3) Scientific-theoretical

Early 1900s to today

A modern milestone was the 1918 book Diet and Health with Key To The Calories by Dr Lulu Hunt Peters. While the word “calorie” was invented in 1820s France and came into English in the late 1800s, it was in this book, the first bestselling diet book — 2 million copies sold — that Dr Peters first brought the concept of calorie as a unit of food energy to mass awareness.

It was so new that she had to define the word calorie, and how to pronounce it, early in the book.

“Definition to learn: CALORIE; symbol C.; a heat unit and food value unit; is that amount of heat necessary to raise one pound of water 4 degrees Fahrenheit.”

The book was sensitive to the fact that for many, food was scarce, and included “the right methods of gaining weight, as well as those for losing weight.” It gives the impression of a good-faith effort to educate, on scientific principles, saying that “the lack of knowledge of foods is the foundation for both overweight and underweight”.

A few years later, Wilbur Olin Atwater was the first person to calculate metabolic rates and the amount of calories burned in various activities. After he produced a "calorimeter” to measure the utilization of energy, the concept spread further, eventually becoming legally enshrined and commonly used in the food and restaurant industry, with labeling on boxes and menus.

Peters and Atwater laid the foundation stones of today’s mainstream “calories in, calories out” (CICO) model of energy, whose grounding metaphor is the human as a “machine”, food as the “fuel”, with the macronutrients — fats, proteins, carbs — as different “types of fuel” (like diesel and petrol for cars) that each yield a certain number of miles to the gallon. The “miles” in this metaphor are calories.

This scientific-theoretical approach has plenty of “faith-based” elements, to be sure, and tribes promoting one view or another. Probably the most clear battle lines between tribes are in the macronutrient mix they espouse: keto, paleo, low-fat, low-carb, and so on typically recommend different percentages of the key macros that “should” be eaten.

Why this model is broken

Before we move on to phase 4, the pharmacological approach to obesity, it’s worth looking at why the scientific-theoretical approach has failed so badly.

First, the science only deals with generalities. Even if, in theory, the CICO (calories in, calories out) model were correct — which I don’t believe it to be — it is highly abstract, and when trying to apply it to individual bodies, the people looking to reduce weight, who are specific and unique, it fails. So all the “one size fits all” diet programs say that “in theory, you, the customer, should lose weight” — but in practice they don’t work. One size fits none.

Second, the empiricism also works at a general level, but is not testable or measurable for a single individual. You can’t “A-B test” one packaged meal with 520 calories vs another with 480 calories on an individual person. You can only average them out, for example, to say “the average person in a group of 100 people who ate the 480 calorie meal vs the 520 calorie meal, lost weight”. But that does nothing to help an individual decide “what calories are right for me”, to avoid the all-too-common process of over-restricting and then suffering and then falling off the wagon, that dooms so many diets.

Third, the generalized metrics and measurability are bogus. Because the process of measuring calories in food — the bomb calorimeter — is crude and impractical, the end results are hopelessly inaccurate. In fact, the calories on a food label have a margin of error of around 20%. Imagine if a bathroom scale told you “you weigh 100kg, but it might be 80kg or even up to 120kg?” You’d throw it out and angrily demand a refund.

(There is a fourth reason I’ll write about separately, which is that the calories paradigm is pegged to the wrong law of physics. Instead of the conservation of energy law, we should look to the conservation of mass. Food going into your mouth is only potential energy, not calories, which are a unit of heat, that happens at a later stage, as the body ‘burns’ the food. As it’s eaten, it’s better measured as mass not “energy”. More on that later.)

The scientific-theoretical approach to weight loss failed, and today we have an obesity crisis of epic proportions – and a pharma industry pouncing on the failure.

It’s for these three reasons above that the scientific-theoretical approach to weight loss failed, and today we are faced with an obesity crisis of epic proportions. This failure, and the size of the potential market, at least 650 million people, and probably a lot more, that opened the door to the next phase in weight loss, the pharmacological approach to obesity.

Pros

Through experimentation, and extending the application of drugs like Metformin that had a positive impact on blood sugar (glucose) levels, the pharma industry has now launched a range of GLP-1 agonists that mimic a hormone in the body and affect various endocrine and digestive processes, with a net result that people feel less hungry less often, and when the do eat, they eat less.

The GLP-1 meds are injectables, either weekly, or daily, and have some side effects, which many people don’t like, but the good news is that they show efficacy against obesity in a way that the scientific-theoretical could not. The trials of Wegovy showed around 15% weight loss over a year.

While I believe the downsides to outweigh the benefits (details below), I fully understand how the pharma weight loss approach will be attractive to many people who have struggled and failed to lose weight many times, who feel dejected, and whose health is suffering.

Compared to a heightened risk of diabetes, cardiovascular disease, or other common comorbidities of obesity, the chance to “kick-start” a weight loss process and move out of the “danger zone” is an appealing one, especially given the total failure of the 20th Century's scientific-theoretical approach to weight loss.

Cons

“But what’s not to like?” say many people. I’ll go into detail in another post, but in brief, the main issues are cost, recidivism, short-termism, and side effects. There are also unknown long-term risks, as well as personal factors issues, like frequent injections many people don’t like.

Cost is a major issue, as the list price for Wegovy, the most advanced GLP-1 med on the market, is $1349.02 for a month’s supply. Novo Nordisk offers some discounts in non-US markets, and for those in the US whose insurance does not cover it, but it is very expensive.

It is only temporary salve, and recidivism levels seem to be almost 100%. The very high price is made worse by the fact that you have to take GLP-1 meds forever, or the weight will come back. Because you are injecting an “artificial support” for your satiety systems — you are mitigating the effects of food choices that resulted in obesity, rather than changing those choices — the body, once the artificial support is pulled away, reverts to its prior state. Same behaviors, same end result.

The quick-fix mindset derails real change. Like so much marketing in modern life, the promise of a “quick fix” or a “silver bullet” for obesity has equal and opposite downsides. While pharmacological interventions can dull appetite and slow metabolic processes, they come at a cost of deferring real change and understanding of the body. The only truly long-term, sustainable way to lose weight and keep it off is to gain an understanding of your body, the foods you put in, and the impact those have on you. The quick fix of injections is like using a crutch rather than mending a broken leg.

Side effects and inconvenience can be a barrier. The FDA lists “nausea, diarrhea, vomiting, constipation, abdominal (stomach) pain, headache, fatigue, dyspepsia (indigestion), dizziness, abdominal distension, eructation (belching), hypoglycemia (low blood sugar) in patients with type 2 diabetes, flatulence (gas buildup)” and other side effects, which are perhaps unsurprising when injecting large volumes of hormone agonists.

There are also many unknown long-term risks. There have been no long term studies on GLP-1 injections, including lifetime impact analyses; no study on the vacuum created by forcing a set of physiological reactions in the body, and no pleiotropic impact studies of effects on the biome or other systems. Lastly, as a personal preference, many people don’t like or want to inject themselves with syringes.

The bottom line is that, while unquestionably more effective than the fad diets or false empiricism of the prior, there are significant problems with the GLP-1 medications, and downsides to consider.

This last point – the limited metrics – is the key difference between the pharmacological approach, and the next era, the data-driven, technological approach to reversing obesity.

Data-driven (scientific-empirical)

2020s–

While the scientific-empirical phase of weight loss systems appealed to scientific concepts at a theoretical level — the conservation of energy, the measurement of energy in fundamental, fungible units, like calories — practical application in everyday life was difficult or impossible. Its Achilles heel was that these theoretical science concepts were useless in practice.

If you tried to count calories going into your body, you start off with a 20% margin of error on the food packaging, and it only gets worse from there. Each body processes food differently, and as soon as food goes into the mouth, it disappears off the radar. All metrics cease until you step on the scale, which is an extremely crude way to measure something as dynamic as the human body and microbiome, in constant flux.

Without any working radar, eating food means flying blind, and “if you can’t measure it, you can’t manage it”. This is where the technological, or scientific-empirical phase begins.

“If you can’t measure it, you can’t manage it”

In 2017, there was a breakthrough that made the data-driven tech approach to obesity possible: the first mass-market CGMs (continuous glucose monitors) went on sale. Like GLP-1 meds, CGMs were aimed initially at diabetics, but have expanded to much wider utility among the general population.

Wearable technologies in general usually start niche and pricey, then over time become mass-market and affordable. This already happened with fitness trackers like Fitbit and Apple Watch, which can today measure 24-7, inexpensively, a set of metrics — heart rate, blood oxygen, temperature, ECG — that used to need a huge, expensive machine in a hospital lab.

Accessible CGMs opened the door to the technological weight loss era. Just as the body regulates oxygen, water, and body temperature, it aims to keep our blood glucose (BG) within a fairly narrow range: if it’s too low, we risk not having energy reserves (eg to run away from a predator) but if it’s too high, for too long, it’s toxic.

Because our modern diet is high in sugars and carbs, most people spike their glucose levels several times per day, causing the body to regulate its system due to this excess energy — blood glucose above the normal range — to be pulled out of the bloodstream and stored away as indirect potential energy within the body, in the form of glycogen or fat.

By measuring the real-time changes in blood glucose, we finally have a ‘radar’ to see inside the body, and steer our choices.

By using a CGM in conjunction with other wearable data — heart rate, temperature and so on — to triangulate how the body is reacting to food, along with exercise, sleep, and all other environmental conditions of that specific body, we can create the first data-driven weight loss system.

This “radar” for the body, with blood glucose at the center, is the first time in human history that we can navigate our healthfulness with total confidence in the outcome. Rather than a fundamentally retrospective analysis of a person’s health — guesswork about calories, or “take this injection and see what happens” — the data-driven approach opens the door to real-time analysis, steering to better choices, and curing us instead of just “covering up” the symptoms.