Chapter 59
Obesity and Diabetes — 18
Only one comparable breakthrough class of medications seems obvious to me, cardiologist that I am—statins. They are taken daily by an estimated two hundred million people around the world, with considerable regional variability by income status of countries. About fifty million people in the United States take a statin, even though its population only accounts for 4.2 percent of the world. That huge number of statin takers is in the same ballpark as the number of Americans who are currently eligible for GLP-1 drugs. There are many parallels between GLP-1s and statins from which we can learn.
Ilove the term pleiotropic, which is frequently used in medicine to explain things we don’t understand. Instead of just fessing up that we don’t know, this fancy word makes it seem more scientific—that the medication has multiple effects, and we don’t know which one, or some combination of them, that accounts for the benefit. This is quite true for both statins and GLP-1s. Nevertheless, they both feature a reduction of inflammation, as seen by biomarkers like hs-CRP. And inflammation is the final common pathway for most chronic diseases, spanning from cardiometabolic to neurodegenerative.
It is hard to parse out that impact from other effects: such as lowering LDL cholesterol by statins or improving glucose control by GLP-1s. What’s surprising is that both classes of drugs have substantially unknown mechanisms for most of the good they do. (Meanwhile, we tend to insist on explainability of artificial intelligence before it can be used in health care, holding it to higher account than we do everyday treatments.)
The expectations for GLP-1s in 2023, after showing reduction of heart and kidney disease, became outlandish. Soon after positive results from these clinical trials, financial analysts projected that we are at the beginning of the end of obesity, heart disease, type 2 diabetes, sleep apnea, and kidney disease. This exuberance is understandable but irrational. Sure, there might be billions of people who could benefit from GLP-1 drugs, but the number of people who will take them is only a tiny fraction. That’s not just because of cost, access to prescription, and limited supply but also because many people can’t tolerate the drugs due to their gastrointestinal side effects. Likewise for statins, there are a substantial proportion who get muscle aches and cramps, intolerance that leads to discontinuation.
The first statins—lovastatin (Mevacor) and simvastatin (Zocor)—were commercially released soon after I started practicing cardiology in the mid to late 1980s. I’ve had the chance to watch their transformative but incomplete impact over the next four decades. A study reported in late 2023 demonstrated that the proportion of guideline-eligible adults taking statins plateaued at only 35 percent over two decades. These were people who should be taking a statin for primary prevention, meaning they had a high LDL cholesterol but no cardiovascular disease, type 2 diabetes, or a high-risk score for heart disease. Even among people with an LDL greater than 190 mg/dL, which is exceptionally high, less than half were taking a statin.