So here is the cynical, and often accurate, view of drug development. A promising compound is found, early animal and human trials show good efficacy, so you move on to Phase 3 trials–the large pivotal trials that will be used to support your FDA application for approval. Your early Phase 1 and 2 trials have given you some indication of people who are most likely to benefit and those who may be less likely to do so or who are more susceptible to adverse events. You want the best results from the trial, but you also want to maximize your “label” from the FDA–you want the broadest possible set of disease indications and populations that are eligible for treatment and you want to minimize sub-groups deemed as not appropriate for prescribing.
So you design your eligibility criteria and your screening for patients who go into the trial to reach those dual outcomes. This shaping of patient populations used in these large approval trials is the critical element in study design and execution. But it also means the drugs aren’t tested on a fully representative sample of the American population. And I can assure you that after approval, the drug company will be spending millions and millions of dollars on advertising to persuade every American that they need the drug and to get doctors to prescribe the drug as widely as possible.
And the end result of this is multiple examples of prominent new drugs that are approved and go into use and then run into serious safety issues because they are prescribed for people who weren’t adequately represented in the trials. The COX-2 inhibitors for arthritis, Avandia and other medications for diabetes, and fen-Phen for weight loss are a few examples of this phenomenon. This is a long lead-in to a recent study on the new weight-loss drugs, which I suspect may also fall into this category. The precursors to these drugs have been around for a long-time and used for some diabetes patients. But whether they have been adequately studied in representative populations now that they are being prescribed for just about anyone with a weight problem is an open question.
And this study suggests that there is reason for concern in regard to the GLP-1 drugs. The study was conducted in the Veterans’ Affairs health system and looked at patients with diabetes, which was the original indication for this class of compounds. While use of these drugs was associated with lower incidence of some conditions, it was associated with a higher risk for others, including gastro-intestinal and kidney disease. Given the widespread use of these drugs for anyone who is overweight, comprehensive ongoing safety studies and monitoring is critical and ensuring the patients understand all the risks is equally important.
Losing weight is hard. I am overweight. It isn’t easy to implement the combination of diet and exercise changes to get into a healthy weight range. Weight loss drugs could be a a helpful tool on that journey. But as with any drug there should be a full and careful study of potential side effects. The FDA also needs to do a far better job of having labels that more precisely describe what sub-groups are appropriate for prescribing and needs to monitor doctor’s prescribing behavior. And one thing RFK, Jr. is absolutely right about is that we need to ban consumer advertising of drug products and regulate more tightly how manufacturers market to physicians and other prescribers.
A couple of things.
1) For weight loss try Noom. No drugs. No tricks. No special foods, supplements or diets. Just eat better, eat fewer processed (thinking foods with added fats and sugars and lots of simple carbs) foods, and get better exercise. And follow their lessons. No banned foods and no required foods. Just eat a small piece of chocolate cake if you have the craving for some. It works. But it’s not easy. I use it and have lost over 35 pounds and am much healthier for it.
2) I think this article tangentially hits on what Sharyl Attkisson and others write about: the FDA and regulatory bodies are full of scientists who either worked for drug and vaccine companies or get grants from them, or who want to work for them later in their career. “Independent” foundations who do research have lots of staff, etc., who’ve worked for pharma or who get grants from pharma. Now this isn’t bad per se, but when there’s little independent research to investigate pharma’s claims then we’re mostly getting one-sided looks at drugs and few, if any, are doing actual science to replicate their claims and challenge their findings. And then because of this insiderism there isn’t push back on making sure we test things on whole populations, which is your valid point. When this happens in energy, for example, we’re told their research is invalid because “Exxon funded it.” But of course there’s a whole environmental industry ready and willing to go after Exxon and energy companies, yet there’s no real equivalent with pharma.
3) Checks and balances are few to none as a) media make a ton of money off of pharmaceutical ads and they could face loss of ad revenue if they are tough on pharma b) government regulators are in the money train, either coming from pharma or planning to go to pharma or, like Dr. Fauci, make royalties off of pharma and c) congress is bought by pharma (it’s laughable to see Sen. Warren badger RFK Jr. about taking drug company money when she is one of the largest recipients of drug company money) so they won’t hold them accountable.