Why GLP-1s could become the "everything drug"

• While it may be tempting to think of them as wonder drugs, there's a lot that's still unknown. It's still not clear whether they're a cure-all, or whether the benefits come from the fact that obesity and diabetes give rise to so many other health problems.
• At over $1,000 a month, GLP-1s are also driving up costs in the health system, and their benefits can go away if patients discontinue the medications.

State of play: The injectable drugs' potential beyond weight loss was driven home early this year by a study of almost 2 million Veterans Health Administration patient records that found GLP-1s lowered the likelihood of dozens of health conditions.

• Researchers found the benefits were modest — about a 10% to 20% reduction in most cases — but noted that could be meaningful, especially for conditions like dementia that have few effective treatments.
• "Given the drugs' newness and skyrocketing popularity, it is important to systematically examine their effects on all body systems — leaving no stone unturned — to understand what they do and what they don't do," Ziyad Al-Aly, the study's senior author said.

Friction point: The Food and Drug Administration has only approved GLP-1s for obesity, Type 2 diabetes, heart risk and, under certain circumstances, sleep apnea. That means using them for any other condition is "off label" and at a physician's discretion.

• The designation can affect whether insurers pay for the treatments. That's no small matter when the monthly cost of brand-name options like Wegovy and Zepbound range from $1,000 to $1,350 without coverage. (Novo Nordisk, maker of Ozempic and Wegovy, notes that most people don't pay those prices, and that almost 90% of patients with coverage for Ozempic pay $25 or less).
• The hype around the drugs has sent many Americans to telemedicine companies that sell brand-name or knockoff GLP-1s. One recent study found that nearly 40% of GLP-1s approved by the FDA for diabetes are being prescribed off-label.
• Meanwhile, drug supply shortages and patchwork health plan coverage policies have made GLP-1s less available to patients most in need, including those in marginalized communities.
• Dozens of lawmakers in Congress last week pressed the FDA to take action against illegal, counterfeit versions of the active ingredients in Ozempic and Wegovy.

Reality check: While the drugs have enormous promise, they come with significant side effects, including increased risk for gastrointestinal disorders, low blood pressure, kidney stones and pancreatitis.

• Surprisingly for weight-loss treatments, there can be a higher risk for arthritis, possibly due to loss of muscle and bone mass.

• More than 36% of patients who start GLP-1s for either obesity or diabetes treatment stop taking the drugs within a year, according to one study. The cost and adverse effects are often cited as reasons.
• And although GLP-1s could lower future health costs by preventing more health problems, expanding Medicare coverage of the drugs could drive up federal spending by $48 billion over the next decade.
• The pricey drugs are already contributing to increasing premiums for employer-sponsored health insurance.

The intrigue: The action of GLP-1s could tell us more about how the brain works, by the way they appear to tamp down inflammation and protect nerve cells.

• They also control cravings and feelings of satisfaction — qualities that could make them important tools for treating substance abuse, suicidal thoughts and even schizophrenia.

So, should we all be taking them? The consensus among many clinicians and researchers is "no," or at least not until more is known about how they work.

• "While I'm excited about the future of these drugs' development, the side effect profile isn't worth the risk for otherwise healthy patients," author-journalist Derek Thompson wrote recently in a Substack review of recent developments and interviews with researchers.

What we're watching: Drug companies are moving to develop GLP-1s in pill form, which would make them easier to take and potentially keep people from cycling on and off as much.

• But insurers will likely remain wary of covering them for new uses without more safety studies and FDA approvals.