Here’s what we’ll cover in this blog post:
- The results of our latest scientific trial
- What is Canagliflozin
- Blood sugar’s role in aging
- How Canagliflozin boosts longevity
Within the longevity community, there have been whispers of a potential longevity drug that may rival Metformin as the new go-to for extending healthy lifespan. That drug is Canagliflozin, a medication FDA approved to treat diabetes just like Metformin.
Though the longevity promise has been published for years in both model organisms and observational studies in diabetics, no clinical trials have explored the potential of Canagliflozin as a geroprotective agent. Does it really work to promote healthy longevity in normative aging individuals? Is it safe for healthy, non-diabetics to take? And if so, what doses are most beneficial?
To evaluate Canagliflozin’s viability for longevity, AgelessRx’s Applied Science team launched a pilot study that examined its short term safety and effectiveness in healthy subjects—a critical first step before exploring whether its beneficial actions go beyond disease therapy to support disease prevention.
The Role of Blood Sugar in Aging
Biological aging is one of the biggest risk factors for cardiovascular disease, cancer, and age-related diseases in general. One of the primary accelerators of the aging process? High blood sugar levels.
Blood sugar, or glucose, is a measure of how much sugar is in our bloodstream. Blood helps transport sugar throughout the body to provide fuel and energy to our cells. A goal of maintaining blood sugar above a certain level (80-95 mg/dL) is considered normal and healthy.
But when there’s too much sugar in our blood, pieces of the sugar peel off and stick onto proteins and blood vessels, changing their appearance and causing our immune system to attack our own body and generate a chronic inflammatory response. This knocks our hormones and metabolism out of harmony, which accelerates aging at a cellular level.
Foods and drinks with high levels of refined sugars, like soda, or starchy carbohydrates can lead to elevated blood sugar levels temporarily and over time if they are consumed regularly. If our blood sugar is too high for too long, it can lead to internal damage and increase our risk for age-related diseases such as diabetes and even Alzheimer’s.
In an age of ultra-processed foods, even “health” foods can have hidden sugars with long-term disease repercussions, making it difficult for many to maintain healthy glucose levels. That’s why nearly half of all Americans may be living with prediabetes and diabetes without even knowing. It’s also why blood sugar maintenance is a huge focus of longevity-medicine.
Canagliflozin and Prevention
The biggest problem with blood sugar? We sometimes don’t know there’s a problem until it’s too late.
In healthcare, it’s most common for doctors to treat disease as symptoms occur. But the symptoms of diabetes often develop silently, years before they become noticeable. We may sometimes notice vague symptoms like exhaustion or brain fog, but the real damage comes from insulin resistance, which causes accumulating damage over time that can have long-term repercussions for our healthspan. So, how do we prevent this silent damage if we don’t know it’s happening?
That’s where Canagliflozin comes in. Canagliflozin works to lower blood sugar through eliminating excess sugar in urine, which could help reliably lower blood sugar for healthy adults, thereby reducing the risk of diseases like diabetes. If taken as part of a healthy longevity regimen, Canagliflozin could stifle risk factors of diabetes before they become risks at all. And given insulin resistance is the gateway for so many other pathological conditions, including the 4 Horsemen of Death which encompass cancer, diabetes, heart disease, and Alzheimer’s, the longevity potential is substantial.
But while Canagliflozin is most frequently taken for diabetes, new studies have suggested that it can activate similar processes to caloric restriction, one of the most well validated interventions for extending lifespan across organisms studied, including yeast, worms, flies, mice, dogs and primates. Other studies have shown that Canagliflozin can effectively boost metabolism and extend lifespan in mice. In humans, studies have shown that SGLT2 drugs may boost cardiovascular and kidney health, in addition to glycemic control.
That’s why our Applied Science team, headed by Dr. Stefanie Morgan, set out to investigate these questions around Canagliflozin. The results could give researchers and healthcare providers a roadmap for safely administering Canagliflozin and exploring its potential as a geroprotective agent.
Study Design: Canagliflozin’s Effects Examined
Run by AgelessRx, this trial explored a group of 24 healthy subjects who received Canagliflozin off-label under one of two dosing regimens: either 100mg a day for 7 days, or 150mg every 48 hours over 7 days.
Each subject had their blood sugar levels measured around the clock with a continuous glucose monitor (CGM) and provided regular self-evaluations. The researchers measured participants’ sugar-urine content to determine Canagliflozin’s efficacy for promoting the elimination of excess sugar from the body, and by proxy, exploring its potential for targeting the longevity-promoting molecular pathways activated by caloric restriction.
Main Findings
- Notable Urine Sugar Elimination
Some subjects eliminated as much as 2.1 grams of sugar in a single urine sample, even 24-48 hours after stopping therapy. For the average healthy individual, this could translate to eliminating up to half a can of soda from the blood each day! - Same Effects with Reduced Dosing
Each dosing group eliminated about the same amount of sugar, regardless of the dose strength or frequency of administration. This suggests that every other day dosing is just as effective as daily, paving the way for personalized dosing schedules hand-tailored to fit the patient’s unique physiology and health goals. - No Notable Negative Effects
No participants displayed any notable side effects, such as hypoglycemia or hypotension, and all participants seemed to tolerate the medication well. - Personalized Response to Canagliflozin
There were substantial differences between individuals in how much sugar was eliminated in response to Canagliflozin. This highlights the importance of taking a personalized approach, as two people may respond differently to the same dose of medication, and there are likely no one-size-fits-all solutions.
Implications for Longevity and for Next Steps
This preliminary report raises significant questions about Canagliflozin’s future use in metabolic health and aging. Notable points include:
- Eliminating excess sugar in the urine alone can have positive impacts on metabolism, inflammation, and organ health, including the heart, brain, and kidneys.
- Intermittent dosing could become a useful long-term therapy option to minimize side effects while maximizing effectiveness for promoting healthy aging.
- Longevity scientists need additional studies to determine optimal regimens for healthy, non-diabetic subjects who desire longevity therapies by evaluating healthspan outcomes, including cognitive function, immune health, and quality of life.
- Long-term follow-up and larger studies, including assessments of changes to molecular biomarkers of aging, organ health, and functional outcomes, will clarify personalized factors unique to a given individual’s lifestyle and physiology that will help predict who may most benefit from Canagliflozin for healthy longevity.
Looking to the Future
The intersection between biological aging and metabolic health is a burgeoning field, and Canagliflozin is one such therapeutic direction that deserves future study. Though this study paves the way for promising research, the community needs more studies to unravel the true longevity potential of Canagliflozin.
Ongoing investigation will also reveal more about the role of SGL2 inhibitors, blood sugar regulation, and so called “caloric restriction mimetics” in aging and long-term maintenance of healthspan. Through focused interventions that target the molecular pathways that mediate longevity-enhancing benefits, these studies are providing more clarity into how these substances influence our longevity. And that’s the true value of these research efforts: not only to validate potential longevity-enhancing interventions, but to reveal the inner workings of our body, allowing experts to know more about what helps us age best.
As the Applied Science team initiates more studies, keep an eye out for a potential new Canagliflozin offering from AgelessRx, and explore our other scientific efforts on our Research Science page. Our team is always recruiting for the next study, and you could help champion a new wave of healthcare for yourself and others like you.
Note: The above statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.