Developing GLP-1 Weight Loss Drugs was ‘Harder’ Than Detecting Gravity Waves

I don’t think it’s possible to overstate how big of a deal these GLP-1 weight loss drugs are, the primary two being Mounjaro (tirzepatide) and Wegovy (semaglutide). Although these drugs have only been on the market for a couple years, there are already large communities discussing them. In all likelihood, actual usage is probably a lot higher than reported usage. There is still a sort of social stigma associated with weight loss drugs. It’s like saying, “I need a $1,000/month drug because I lack the willpower to put the fork down.” The same for cosmetic surgery. People like to show off the results of having had surgery, but are secretive about actually having undergone it, in which there is still a stigma. Successful cosmetic surgery looks like having not underwent any obvious surgery at all.

But if only losing weight were so easy. Putting down the fork is easy, but keeping it down is the challenging part. There have been many stories bemoaning how science studies fail to replicate–the so-called ‘replication crisis’, but the overall futility of diets is one of the most persistent and well-replicated findings of human biology. People may lose weight initially, and then regain much of it 2-3 years later, assuming much weight is lost at all. As I wrote earlier, these drugs are a game changer in the battle against obesity, as nothing short of bariatric surgery has been shown to work at producing long-term weight loss.

It’s not like debating mask or lockdown efficacy or how well vaccines worked at stopping Covid, in which both sides can readily summon convincing studies for or against their respective positions by cherry picking cities or counties in which masks worked or failed: the evidence is close to incontrovertible for all demographics and other variables that diets do not work except for maybe a small percentage of the population.

To get an idea of how advanced these drugs are, the detection of gravity waves by LIGO (Laser Interferometer Gravitational-Wave Observatory), as predicted by Einstein’s theory of general relativity, preceded Ozempic by five years, in 2015 vs 2020. And then Mounjaro, which came to market in late 2021, developed by Eli Lilly, which is even more powerful. To put this in perspective, the detection of gravity waves entailed precision comparable to “measuring the distance to the nearest star (some 4.2 light-years) to an accuracy smaller than the width of a human hair…”

Yes, measuring a cosmic hair was easier than developing a safe (as far as we know based on GLP-1 use dating back to the early 2000s for diabetes treatments, and clinical trials), non-stimulant, non-addictive, and effective weight loss drug. And this is despite the backing of multiple muti-billion dollar corporations and huge demand for weight loss drugs as a market incentive, and still it took a really long time. The development of weight loss drugs goes back a century, such as DNP (repurposed as a weight loss drug, but with lethal consequences for some users), phentermine, etc. Federal or state-backed science budgets are comparably paltry, and no market demand.

The usual objections are like, “But people were much more lean hundreds of years ago. Can’t we adopt their lifestyle?” True, but average life expectancy was only around 40-50 at that time, and not just due to childhood and infant mortality. It’s easier to stay lean when you are sick with infections or competing with intestinal parasites for nutrition due to spoiled food. It would seem as if rising rates of obesity tracks modernity and rising lifespans. (And perhaps we’re at the point in which obesity has become so bad that it begins to lower life expectancy.) As people live longer, especially past 40, obesity rises. This is is seen all over the world, even in Africa, in which countries like Nigeria have obesity rates comparable to parts of the US now (14-17%).

But these drugs are not miracle drugs, and are not without potentially negative side effects such as nausea, nutritional deficiencies, and muscle loss. Efficacy is variable. The typical weight loss is 13-25% of starting weight, but this varies considerably. From what I have read, about 10% of individuals lose little to nothing, and others lose a much higher percentage. Success stories online of substantial weight loss may influenced by survivorship bias: people who lose little or no weight are going to be less inclined to share their progress.

The true ‘miracle drug’ or game changer will be a safe, non-addictive metabolism booster, similar to DNP but without the accidentally ‘cooking your body to death’ aspect of it, or heart problems and addiction from stimulants. A metabolism booster will bypass some of the potential muscle loss and nutritional deficiencies of GLP-1 drugs by allowing people to eat full meals without the nausea and other problems that arise from delayed gastric emptying from Mounjaro and similar drugs. In the battle against obesity, society needs all the help it can get. Given that it took 100 years to get to where we are now in which third of the nation is obese, the timing could not have been better, but owing to the complexity of human biology it may be a while before we see another breakthrough.