Thoughts on Weight-Loss Drugs and Trust in the Scientific Enterprise
An email from a colleague nails the tension regarding use of the new drugs for obesity.
I am in Copenhagen and Aarhus speaking about medical evidence. One of my talks will argue that cardiologists should treat obesity.
This morning I received an email from a cardiologist who is struggling with the new data on the GLP-1 agonist drugs. It’s a timely note—as Copenhagen is home of Novo Nordisk, the makers of semaglutide. My sample is small but it seems the company has built trust among my Danish colleagues.
That said, I struggle with how to apply the medical evidence. The effect size and reduction in important outcomes with the GLP-1 agonists are clear. But. There is the matter of trust and long-term effects.
I don’t (want to) share my colleague’s super-negative view of academia. Yet I publish this note because it demonstrates the importance of trust in science.
Here is the email. See what you think. I hope the writer is wrong. JMM
My name is *****. I am a cardiologist outside of (a big US city).
I am writing as I wanted your opinion. I am still very apprehensive about the glp1 agonists. Many patients come and ask me for them and for the most part I tell them my apprehension—including the fact that they don't change behavior and a lot of my patients who got the medicine somewhere else put the weight back on once they stopped it.
I can't erase the original trials increase in pancreatic cancer in my head not to mention the link with thyroid cancer and pancreatitis.
Trust in academia has also fizzled for me. I have come to realize the ACC and AHA conferences have turned into giant marketing campaigns. They are cranking out studies left and right about the weight loss, which I admit is great, but I am still skeptical, as I can totally see them either hiding the data of harm or simply performing the study in a way that it is not recorded. I hate to say the movie Fugitive reminds me of these things. We have seen major Cardiology trials also have fraud.
After all, they are making boat loads of money.
It's sad. When I was a fellow in 2007 I felt like when some things got approved it had to go through a gauntlet of skepticism. Now it just gets pushed through by money, manipulation and statistical acrobatics.
On the other hand, I also don't want to deny my patients a potentially good treatment because of my bias and skepticism.
Again, I have seen all the recent trials, but unfortunately I don't trust them.
I am using my medically conservative rule I learned from a great teacher of mine: don't prescribe a new drug unless it's been on the market for at least 3 years. I know it's been there since 2015 but now with millions of people on it for weight loss I am waiting for either the bombshell to go off or that I am wrong.
I was hoping you have some insight to either tell me I'm nuts for my thinking or tell me don't deny your patients.
Trials like Step-HFpEF were indeed naked marketing exercises, and did not move the needle at all for me.
But much harder to ignore SELECT. I will say I’m less impressed with a BMI of 27 (the inclusion criteria), but when you get to a BMI of 33 (average among actual participants in the study), I feel that constitutes a more intractable health problem that may justify medical intervention, especially in a secondary prevention cohort.
I still use euphemisms like “take this pill, and take it out for a walk daily”. But I have to acknowledge that significant overweight becomes a vicious cycle that precludes pts from being able to do adequate exercise. And so you have to break that vicious cycle somehow. And this drug may be one way.
I must say I do share the email author’s cynicism in many ways. I am dismayed that the major societies (and their guideline writers) have become nothing more than cheerleaders for pharma. I’m not sure how to put that genie back in the bottle.
My version of medical conservatism is to apply the data on patients that look like those who were (or could have been) enrolled in a study. I’ll use a drug on someone who looks like someone who could be a study subject. But I refuse to extrapolate to the kitchen sink (like latter day guideline writers seem so keen to do) in the name or service of knowledge translation.
However, I would stop short of alleging fraud, as the email author seems to be doing. I can believe it happens from time to time; but I don’t think it’s anywhere near as ubiquitous as to require essentially rejecting any and all study data.
I never have and never would recommend drugs for weight loss. Absent any hormonal abnormalities, the physiology of weight gain and loss is pretty simple. Take in more calories than your body expends and you will gain weight. Burn more calories than you ingest and you will lose. People may have different levels of basal metabolism that may make this more difficult for some. I found that those most successful in losing weight were those that followed a low carbohydrate diet---probably because the relatively high fat and protein content seems to enable most people to cut the calories with less hunger pangs and cravings. There are dozens of variations in this diet with different names (and best selling books) every few months or so. But they are all fundamentally the same. Of course this sort of diet is anathema to those who preach the low fat, low cholesterol diet and causes great angst for those who wish to simultaneously advocate these contradictory positions on diet.