Will-Power and Pill Power

AI image, with Nightcafe

In the dying days of 2024, we visited a dear friend who has struggled with his weight for as long as we have known him. He was an early proselytiser for the keto diet, had dived deep into the physiological mechanisms which make it effective, and, more to the point, had lost fifteen kilograms when he “went keto”, to use his phrase.

Or twenty, or twelve… He went keto several times, and it always worked, but he always relapsed. Tempted by biryani, as it were: rice, like other carbohydrates, is a strict no-no in the keto world, which dictates that fat and protein should dominate your daily intake. His experience with his weight reminded me of a joke from my teenage years “Giving up smoking is really easy - I’ve done it dozens of times.”

But obesity, like smoking, is no joking matter, and has serious implications for both the length and the quality of life. My friend needs no reminding of this; unlike many overweight people I know, he was never touchy about the topic, and would often be the first to bring it up. On this visit, he shared the fact that he had just started taking semaglutide, the Novo Nordisk medical compound that has been extraordinarily successful in combating both excess weight, and diabetes.

Every week, twenty five thousand people begin taking Wegovy, the weight loss version of semaglutide in the US. Statisticians believe they are beginning to see the impact of the drug on the average weight in the US, and some observers believe that ‘peak obesity’ is now behind us. About time, too.

The World Health Organization, believes that “obesity has nearly tripled since 1975. In the U.S., 42% of adults were considered obese (2017-2018).” The National Institutes of Health (NIH)* remind us that this is not just a matter of aesthetics or self-image, as “people affected by obesity have a higher chance of developing serious health problems, including asthma, type 2 diabetes, high blood pressure, cardiovascular disease, stroke, and many cancers, which together are among the leading causes of preventable or premature death. Children with obesity may be at a greater risk for allergies.”

Is the drug too good to be true, as commentator Ruchir Sharma* writes in the Financial Times? “As a quick fix for obesity, this could turn out to be just another diet fad”, he suggests. I detect more than a hint of moral superiority here - as a dedicated and disciplined sprint runner, Ruchir has doubtless summoned huge amounts of will-power to maintain his practice even while his work in global investing subjected him to relentless travel, jet lag, and high-level meetings.

I wrestle with the notion of will-power - is it something everyone can summon, or is it a genetic gift each of us have in different measure? I know the travails and triumphs of being overweight. I was a fat kid, and my favorite aunt called me Billy Bunter. At some point, my love of the outdoors tipped the scales in favour of a relatively lean frame, despite my life-long love affair with sweets of every provenance. More times than I care to remember, I have looked down upon people who have not been able to keep their appetite in check - whether for food, alcohol, tobacco or drugs.

Early research* into the effects of semaglutide and other GLP1 drugs suggests that they can reduce people's cravings for alcohol, nicotine and opioids. They may also impact other forms of compulsive behavior, such as gambling and online shopping.

Drugs like Semaglutide don’t just work on blood sugar. "They also work in your brain," says Dr. Lorenzo Leggio, who's the clinical director of the National Institute of Drug Abuse.

"The mechanism in the brain that regulates overeating overlaps with those responsible for the development and maintenance of addiction, including alcohol disorder," he says. "Dopamine in the striatum [the brain's motivation center] is the motivation and learning signal for everything. Not just for food," DiFeliceantonio says. "All addictive drugs increase dopamine there. That's a common thing."

And so after the first taste of beer, the dopamine tells you, "Do it again! Have another gulp."

But studies have found that in animals and people, GLP-1 drugs reduce the release of dopamine in this region when you eat something sweet and fatty, or when you consume alcohol. "The drug talks with our brain and says, 'We've had enough food here. So let's slow down. Let's have less appetite, let's have less food. Less alcohol," says NIDA's Leggio.

Dopamine is also the hormone that gives me - and doubtless Ruchir, too - pleasure when we run*. But it’s not on tap. When I return to running after a longish break, the first few outings are more pain than reward, a struggle to loosen joints, to get the muscles used to repeated strain, and the lungs to working hard and deep. The dopamine reward can take weeks to kick in. For a first-time runner, especially an overweight one, the highs of running are possibly months away. Meanwhile, the instant hit of beer, or a chocolate milkshake, are always at hand

If Wegovy and its imitators can suppress the rewards from gulping calories, with no major side-effects, this is something we must salute as a massive contribution of pharmaceutical science. If nearly half of the adult American population is overweight, all of middle-class India is getting there. After six weeks watching the Indian middle-class on the beaches of Goa, I would venture that we already have an overweight epidemic in India.

There’s no point being sniffy and moralistic about it. If semaglutide can help people lose weight, that’s one way to deal with dopamine. Runners, like Ruchir and me, should thank the randomness of grace that we have others.

• Incidence of obesity

https://www.niehs.nih.gov/health/topics/conditions/obesity

• Ruchir Sharma, the contrarian

https://www.ft.com/content/ff169e88-c415-400f-8a58-5ebdd5d2a643

• Semaglutide suppresses other cravings

https://www.npr.org/sections/health-shots/2023/08/28/1194526119/ozempic-wegovy-drinking-alcohol-cravings-semaglutide

• Running and dopamine

https://www.runnersworld.com/health-injuries/a60410918/running-and-dopamine/