By Alan Cassels at Brownstone dot org.

This is a slightly shortened version of a Feb 26 New York Times article where journalist Katrin Bennhold interviews Dani Blum of the Times' "Well Team" about Ozempic and GLP-1 drugs.

The Fifth Doctor snoops in on the conversation and adds his two cents' worth.

I've known several people who are on Ozempic who lost weight really fast. How exactly do these drugs work?

Dani: …Basically, the drugs mimic naturally occurring hormones that blunt our appetites and leave us feeling fuller, for longer. When people take these drugs, they're just less hungry.

Fifth Doctor: Yes, less hungry, but also potentially more mentally unwell. Mounting reports of anxiety, worsening depression, and thoughts of suicide surround those taking GLP-1s, drugs like Ozempic. While it might be rare that the drugs make you go crazy, the potential troublesome psychiatric effects added to the long list of nasty physical effects makes the treatment intolerable for most patients. These effects are so severe that most patients stop taking the drug and thus a trial of these drugs becomes an expensive failed experiment for most people.

Do people have to stay on them forever to keep the weight off?

Dani: Basically, yes. It's possible, but rare, for people to keep the weight off when they go off these drugs. Even Oprah gained back 20 pounds when she went off them. Doctors I talk to say we should think of these medications like statins — something to be taken long term.

Fifth Doctor: Look, if Oprah can't sustain weight-loss post-Ozempic, what are your chances? Problem is, she probably found out the hard way that the weight comes back but the muscle you've also lost on GLP-1s stays lost, so you may end up in worse shape after you stop the drug than before you started. Also: "What the heck is '"long term?'" At best we have up to 18 months randomized data for current doses of GLP-1s, plus several years of followup from real-world studies, but not decades-long randomized exposure at obesity doses. As for staying on statins "forever," geez, that statement ranks among the dumbest bits of medical advice possible. It would take me a whole article to explain why "statins for life" is a loser's game, so stand by for the Fifth Doctor's advice on that file. But back to these game-changing weight loss drugs.

Do we know yet what the side effects of long-term use might be?

Dani: No, we don't really know a lot about potential long-term side effects yet. We just don't have decades and decades of data. We do know that these medications can have side effects in the short term. Most commonly, these are gastrointestinal issues: nausea, constipation, diarrhea, stomach pain. People can also get fatigued. In rare cases, people can experience more severe problems, like kidney or gallbladder issues, or pancreatitis.

Fifth Doctor: The tip-of-the-iceberg side effects are the ones we know, but like any new, widely-used drug there is that other thorny class of drug effects, the Rumsfeldian "Unknown unknowns" which for GLP-1s, are undoubtedly a minefield. Before you embark on your Ozempic-trip, you have to imagine yourself staring down the barrel of a .44 magnum and Clint Eastwood saying: "Ask yourself, do you feel lucky, punk?"

But at the same time, there seems to be a new study out every week showing GLP-1s help treat various ailments. What's going on there?

Dani: Such a good question. We've seen positive data on how these drugs can help with things like sleep apnea, heart issues and kidney issues…Some think that these drugs can reduce inflammation throughout the body, which could have big benefits. But again, these drugs are pretty new, and there are many open questions.

Fifth Doctor: The caveats are welcome in an ass-covering sort of way, but let's call a spade a spade. Every new study of a new drug is often little more than a marketing opportunity for the companies making them. When the manufacturers control the release of the research, ie: publishing th...