# From Diabetes Drug to Longevity Drug? The Promise of SGLT2 Inhibitors

**Author:** Dr. Frank Lipman  
**Published:** 2026-09-07  
**Category:** Healthy Aging

Explore the emerging science of SGLT2 inhibitors and longevity, from heart and kidney protection to their potential effects on inflammation, metabolism and healthy aging.

As the Boomer generation is hitting their later years and Gen X is closing in fast, one thing is for certain: interest in longevity and all the ways we can help get ourselves there is absolutely massive. There are fascinating new discoveries virtually every days and things are moving at lightning speed. However, one huge bottleneck in longevity medicine research these days is that the FDA takes a dim view of drugs that might be able to treat the effects of aging. It is, after all, in the disease business. For the most part, the FDA reserves its all-important thumbs-up for studies that investigate treating one disease at a time, the proverbial “whack-a-mole” approach. But there is a loophole: drugs which have been approved for one specific indication can legally be prescribed “off-label,” for whatever reason the physician chooses. That’s how metformin and rapamycin attracted so much attention as “longevity drugs,” even as doubts have arisen as to whether metformin really can extend lifespan for people who aren’t diabetic. And long-standing concerns about the toxic side-effects of rapamycin, even at low doses, haven’t gone away. Instead, it’s another class of drugs, the SGLT2 inhibitors, prescribed for type 2 diabetes, that have emerged as leading candidates to push back against not only the “diseases of aging” but, some would argue, the aging process itself. A 2024 review of anti-aging drugs by two leading “geroscience” researchers ranked the SGLT2s as having the most solid evidence behind it . Here’s a top line on the drugs that have the potential to change the way medicine understands, and treats, aging: Where did the SGLT2s come from? Over a hundred years ago, it was discovered that the bark from the apple tree could lower blood sugar. Since then, chemists synthesized and refined the chemical into type 2 drugs which for the past decade have served as metformin back-ups. (These are the “flozin” drugs: empagliflozin, dapagliflozin, sotagliflozin.) But because the FDA had its fingers burned by another class of blood-sugar-lowering type 2 drugs, the sulfonylureas, which actually raised the death rate, it required an unusually large number of studies before it would approve the SGLT2s. That’s when the data started popping that they could be more than just a “second-line” diabetes drug. What the human data’s telling us. People with type 2 diabetes are at high risk for heart and kidney disease so when those first studies revealed not only the expected lower blood sugar numbers but also significant improvements in cardiovascular and kidney health, researchers took notice. Subsequent SGLT2 studies have only reinforced that good news, for instance a meta-analysis that looked at data from nearly 47,000 patients . One stand-alone study looked at some 7,000 type 2 diabetics who were at high risk for heart disease. Not only was there a 38% drop in cardiovascular mortality, but also a 32% reduction in “all-cause” mortality , that is death from any cause. Another large study, looking at patients with both type 2 and heart disease, found an even larger drop in all-cause mortality, 43% . Evidently, the drugs are protecting our vulnerable organ systems in a number of ways. Given that a majority of middle aged and senior Americans have cardiac and metabolic issues -- witness the millions of prescriptions for blood pressure meds, statins and metformin -- the potential for the SGLT2s to grow into the role of multi-purpose healthy aging drugs, true “geroprotectors,” is exciting. How it works, simply…. Researchers still aren’t entirely sure how metformin works, as its blood-sugar lowering ability was discovered by serendipity. The SGLT2s by contrast are a model of simplicity. They block the action of the sodium-glucose transporter protein (that would be the “SGLT” in the name) which is responsible for allowing the body to reabsorb some of the glucose in urine before it gets excreted out of the system. How much? By one estimate, the drugs send about 70-90 grams of glucose a day out with your pee, or about the equivalent of 24 oz. of Coke. And in today’s world, with our high-carb, high-sugar diets, when you take that much glucose out of the system good things happen. What the mice are telling us. The clinical trials have shown us that the SGLT2s have disease-protecting effects beyond what you’d expect from simply lowering blood sugar and improving insulin response. But why? For that we turn to the lab research, most of it done on mice, which gives us a window onto what we think may be happening in the human system. In a recent post on the sirtuin enzymes I explained that our healthspan and lifespan in large measure are determined by the balance our bodies strike between growth and maintenance. By the time we’re mature adults, we want to invest fewer of the calories we consume into adding new tissue and more into running a lean, clean machine. The SGLT2s are our allies. They help us tune down the body’s pro-growth mTOR pathway and tune up the pro-maintenance AMPK pathway . That means we have an easier time getting rid of old, “senescent” cells or recycling them to make high-functioning new ones, a process we call autophagy. Taking advantage of “downstream” benefits. In practical terms, a metabolic tune-up enhanced by the SGLT2s means less inflammation. By reducing the number of senescent cells , they also reduce the inflammation these cells generate, as well, their ability to hang around and clog up the works. Our vessels are particularly vulnerable. Inside the coronary vessels, inflammation helps “arm” cholesterol, sending it down the path of becoming atherosclerotic plaque, capable of triggering a heart attack or contributing to the slow wearing down of the heart muscle itself, a.k.a.heart failure. As well, old, dysfunctional cells contribute to fibrotic scarring inside the vessels, not only inside larger heart vessels but in the tiny ones inside the kidney. Then, consider the mitochondria, power plants inside the cell which grow cranky with age, generating increasing amounts of oxidative stress (our old enemies, free radicals) which contribute to an inflamed, toxic environment. The evidence suggests SGLT2s calm the mitochondria down, making the energy-generating process more efficient and less “dirty.” All of these beneficial effects go a long way to explaining the reduction in heart and kidney disease we see in the human studies. The vessels retain more of their natural suppleness, blood circulates more smoothly through the system, our organs are happier. SGLT2s: the next frontiers. Some of the best recent research looking at neurodegenerative diseases like Alzheimer’s and Parkinson’s has emphasized the role of inflammation and insulin resistance in the brain. Here again the SGLT2s look like an attractive therapeutic, able to cross the blood-brain barrier. The mouse research is tantalizing, especially one 2022 study which found that the SGLT2-treated animals had less inflamed brains that processed insulin more efficiently, exactly the effects we’d want to see in a drug for humans. Cancer is another inviting target. A 2023 Indiana University study found that a group of patients undergoing treatment for non-small cell lung cancer saw their mortality risk drop by 32% , a positive effect in line with what earlier mouse research had suggested. A word to the wise…. As promising as the SGLT2 landscape looks, some caveats are in order. One big one: all the human research has been done on patients in poor health. What, if anything, the SGLT2s might do for people in good health who simply want to stay healthy for longer is just not yet known. And there is a not uncommon side effect of the drugs to be aware of: yeast infections. They happen, sometimes, when you excrete sugar. Also keep in mind that in some of the animal research, females did not respond as well to the drugs as males. All things to keep in mind if your cardiac risk factors are high, especially high blood sugar, and you want to explore the SGLT2 option with your physician.

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