Wondering About Wonder Drugs

By SAM URETSKY

The Food and Drug Administration (FDA) approves 40 to 50 drugs a year. Some are new molecules, while other approvals are of older drugs for new uses. Most don’t get much attention, but some become commercially important. In 1974, Upjohn (now a division of Pfizer), released ibuprofen, the first non-steroidal anti-inflammatory, not counting aspirin, and if seemed as if the drug was a cure for arthritis. It’s not. In 1977 Smith Kline (the name changes a lot) released cimetidine for treatment of ulcers – and then offered a false reason for why the drug’s benefits didn’t last very long– ulcers are actually caused by bacteria

But in 2005 the grail was found – or so it seems. About 1906, Frank J, Kellogg, the brother of the cereal maker, founded Kellogg’s Safe Fat Reducer, and other companies were promising weight loss nostrums, such as Marjorie Hamilton’s Obesity Cure ($15, which would be about $560 today.) At that time, the closest thing to a drug that worked was thyroid extract, which can be dangerous. In 2002 Amylin developed exenatide, the first GLP-1 agonist, and later formed an alliance with Lilly in to bring the drug to market. Exenatide was approved by the FDA in April 2005, for people whose diabetes is not well controlled on other oral medications.

There have been a number of modifications of the original molecule, but in July 2024 the journal Nature published a report that combined two current interests, Artificial Intelligence and GLP-1: Using large language models to assess public perceptions around glucagon-like peptide-1 receptor agonists on social media. The abstract begins: “The prevalence of obesity has been increasing worldwide, with substantial implications for public health. Obesity is independently associated with cardiovascular morbidity and mortality and is estimated to cost the health system over $200 billion dollars annually. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a practice-changing therapy for weight loss and cardiovascular risk reduction independent of diabetes.” They used AI to analyze 390,000 discussions of the effects of GLP-1 in Reddit discussions. The results showed a mainly neutral-to-positive view of these medications, but the analysis of the findings of this large a review may show new side effects not previously seen in clinical nor reported in previous trials. This type of study may even show a direction for further study.

On Dec. 5, 2024, Medscape published a report, “GLP-1s Hold Promise for Addiction but Questions Remain.” While there have not been serious controlled studies of these drugs, there has been chatter about potential use for treating drug addiction and alcoholism.

There have been several drugs in this class, marketed by different names for diabetes and for weight loss:

Semaglutide:
Brand names: Ozempic (for diabetes), Wegovy (for weight loss)
Manufacturer: Novo Nordisk
Semaglutide was the top-selling drug in the United States in 2023, with sales of almost $14 billion

Liraglutide:
Brand names: Victoza (for diabetes), Saxenda (for weight loss)
Manufacturer: Novo Nordisk

Dulaglutide:
Brand name: Trulicity
Manufacturer: Eli Lilly

Exenatide:
Brand names: Byetta, Bydureon
Manufacturer: Eli Lilly

Dual Agonists:
Tirzepatide:
Brand names: Mounjaro (for diabetes), Zepbound (for weight loss)
Manufacturer: Eli Lilly

With the number of GLP-1 agonists and the demand for effective weight loss, there has been interest in which, if any, is the best, with advertising to follow. YouTube is rife with advertising claiming that one or the other is best. Cureus (vol16, no4) published a meta analysis of nine different studies to see if there were significant benefits, one to the other. While semaglutide was marginally more effective at weight loss, there was no stand-out. The authors note that there have been newer drugs in the same general class that have not been available for comparative studies. Mounjaro® (tirzepatide) and Zepbound® (tirzepatide), which act on two different receptors, is apparently more effective at causing weight loss than the other drugs, but there have not enough studies to determine which is most effective, safest, or even cost effective.

Still, it is important to realize that these drugs are generally safe and effective, and a discussion in Medscape (12/6/24) was titled “No, Diet and Exercise Are Not Better Than Drugs for Obesity” which begins, “They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.”

We’ve come along way since Marjorie Hamilton (about 1910) reported “fat is simply thickened nutrition.” It might be called “Indiana Jones and the weight loss remedy that actually works!”

Sam Uretsky is a writer and pharmacist living in Louisville, Ky. Email sam.uretsky@gmail.com

From The Progressive Populist, February 1, 2025

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