GLP-1 Drugs May Change More Than Just Waistlines

GLP-1 medications are usually discussed in one context.

Weight loss.

Ozempic, Wegovy, Mounjaro and Zepbound have become cultural shorthand for shrinking waistlines, quieting “food noise” and changing how we treat obesity.

But that framing is becoming incomplete.

Researchers are increasingly finding that these medications may positively affect the heart, kidneys, liver, brain and other systems throughout the body. Some of these benefits are now supported by large randomized trials. Others remain intriguing but preliminary.

I should make something clear upfront: Unlike some of my other posts, I’m not coming at this from personal experience. I’m too far on the other side of the spectrum - needing to gain weight and preserve and grow muscle mass at this stage in my life. I’m interested because it’s difficult to study longevity without paying attention to a class of medications that is beginning to influence so many of the diseases that shorten healthspan.

GLP-1, or glucagon-like peptide-1, is a hormone your body naturally releases after eating.

It helps your pancreas release insulin when blood sugar rises, reduces glucagon secretion, slows the movement of food through the stomach and signals fullness to the brain.

Medications such as semaglutide mimic this hormone but remain active much longer than naturally produced GLP-1. Tirzepatide works slightly differently, activating both GLP-1 and GIP receptors (another gut hormone that is released after eating to help regulate insulin secretion and metabolism).

These medications don’t simply suppress appetite. They intervene in a hormonal network connecting the gut, pancreas, brain and metabolism.

Once you understand that, their wider effects become less surprising.

The clearest evidence outside of weight loss involves cardiovascular disease.

The SELECT trial followed more than 17,000 overweight adults with established cardiovascular disease. Participants receiving semaglutide experienced a 20% lower risk of cardiovascular death, nonfatal heart attack or nonfatal stroke than those receiving a placebo.

That result was significant enough for the FDA to approve Wegovy for reducing serious cardiovascular events in this population.

Tirzepatide has also shown promising results in people with obesity and heart failure with preserved ejection fraction, a condition that has historically been difficult to treat. In the SUMMIT trial, it reduced the risk of worsening heart failure or cardiovascular death while also improving symptoms and physical function.

These results alone wouldn’t be terribly surprising if it was strictly a function of weight loss resulting in better cardiovascular health. Think about it - the less unhealthy body mass, the lower the strain on the heart. However, the authors of the study ran an analysis accounting for how much weight participants had lost and they still found that 35% - 55% of the cardiovascular benefit remained.

The point is this: these are no longer merely cosmetic weight-loss drugs. They are medications with demonstrated cardiovascular outcomes and I’m personally excited to follow the ongoing research into the purported cardiovascular benefits of GLP-1s.

In the FLOW trial, semaglutide reduced major kidney outcomes by 24% in people with type 2 diabetes and chronic kidney disease. Those outcomes included worsening kidney function, kidney failure and death from kidney or cardiovascular causes.

The liver evidence has also moved quickly.

In the phase 3 ESSENCE trial, nearly 63% of participants receiving semaglutide saw their metabolic dysfunction-associated steatohepatitis, or MASH, resolve without any worsening of liver fibrosis, compared with roughly 34% of those receiving a placebo. Semaglutide also led to greater improvements in liver scarring.

In August 2025, the FDA granted accelerated approval to Wegovy for adults with MASH and moderate-to-advanced fibrosis. Continued approval remains contingent on confirmation of longer-term clinical benefit.

This is an important distinction.

The drug didn’t simply improve a blood test. It produced measurable changes in liver tissue.

This post is sponsored by Resbiotic.

Resbiotic is a science-led microbiome company developing prebiotic, probiotic and postbiotic formulations designed to support the connections between the gut and the rest of the body.

Its resM GLP-1 Postbiotic is formulated to support the body’s natural GLP-1 pathways, appetite regulation and metabolic health.

I respect Resbiotic as the company is lead by a truly high-caliber team of professionals - something that’s critical in an industry where so many products and services aren’t grounded in real science and where the marketed benefits grossly overstate the underlying products.

To learn more about Resbiotic visit Resbiotic.com or learn more at Workup.

One of the most interesting emerging areas involves reward and compulsive behavior.

A large observational study of more than two million veterans with diabetes found that GLP-1 receptor agonist use was associated with lower risks of several substance-use disorders, seizures and some neurocognitive conditions. It also identified increased risks in areas including gastrointestinal problems, low blood pressure and certain kidney complications.

Observational studies can reveal patterns but they can’t prove that the medication caused them.

But a small randomized trial has added support to the addiction hypothesis. Among 48 adults with alcohol use disorder, low-dose semaglutide reduced alcohol consumption in a laboratory setting and reduced some measures of drinking and alcohol craving over nine weeks. It didn’t improve every outcome and naturally the study was far too small to change clinical practice.

Still, the idea is biologically plausible.

If these drugs influence brain circuits involved in appetite, reward and reinforcement, their effects may extend beyond food.

GLP-1 enthusiasm has occasionally drifted toward the idea that these medications might protect against nearly every chronic disease.

The Alzheimer’s research is a useful reality check.

Early observational evidence suggested that GLP-1 users had lower rates of dementia. But in two large phase 3 trials involving approximately 3,800 people with early Alzheimer’s disease, oral semaglutide didn’t meaningfully slow cognitive or functional decline.

The medication improved certain biological markers, but those changes didn’t translate into a clinical benefit.

Cancer research is similarly unsettled.

A 2026 observational study of more than 110,000 women found that GLP-1 use was associated with roughly 30% lower breast cancer incidence after researchers adjusted for several major risk factors.

That’s a compelling signal.

But randomized-trial reviews have generally found little or no clear effect on overall obesity-related cancer risk, in part because most trials were not long enough or designed to detect cancer outcomes.

At this point, nobody should take a GLP-1 medication solely to prevent dementia or cancer.

The research belongs in the “worth investigating” category, not the “clinically proven” category.

Powerful medications come with powerful tradeoffs.

Nausea, vomiting, diarrhea, constipation and abdominal discomfort are common.

Then there is muscle.

In a body-composition study of tirzepatide, approximately 75% of the weight lost came from fat mass and 25% from lean mass. That ratio isn’t necessarily unusual during major weight loss, but losing lean tissue still matters - especially for older adults, people starting with limited muscle or anyone who loses weight rapidly without resistance training and adequate nutrition.

This concern is particularly relevant to me.

My goal isn’t to become lighter. It’s to become stronger and add metabolically useful tissue. A medication that is transformative for someone living with obesity may be entirely wrong for someone with different needs.

There’s also the maintenance question.

In the STEP 1 extension, participants regained approximately two-thirds of the weight they had lost within one year of stopping semaglutide. Many of their cardiometabolic improvements also moved back towards baseline.

That isn’t evidence of weak willpower. Instead, it’s evidence that obesity is a chronic biological condition and that these drugs often function more like long-term blood-pressure medication than a temporary treatment with a clear finish line.

The real story isn’t that GLP-1 medications cure everything.

They don’t.

The real story is that obesity, insulin resistance and metabolic dysfunction affect almost every organ system. Treating those conditions effectively can therefore produce benefits throughout the body.

Some effects may be driven by weight loss.

Some may come from improved blood sugar, lower inflammation or reduced organ fat.

Some may eventually prove to be direct effects of GLP-1 signaling.

And some of today’s most exciting hypotheses will fail when tested in rigorous trials.

That’s how science is supposed to work.

For people with the right medical indications, GLP-1-based therapies may be among the most important healthspan tools developed in decades.

And I for one, am personally excited to be living in an era where we’re increasingly finding ways to move the needle on healthspan.

Yours in Health,

Ryan