Metformin is a widely used medication primarily for treating type 2 diabetes. However, it's also utilized for prediabetic patients and, in some instances, individuals with insulin resistance—a category that encompasses a significant portion of the population. Nearly a three quarter of people fall under the diabetic, prediabetic, or insulin-resistant categories. Therefore, metformin serves an important role in blood sugar control. Interestingly, although not officially approved for these purposes by regulatory agencies, it is also used off-label to enhance fertility in women and as a longevity supplement.

The drug has been in use for many years and is considered a safe option with few long-term side effects. Before delving into the positive aspects, it's important to acknowledge potential side effects, which can include gastrointestinal issues (such as diarrhea, nausea, vomiting, abdominal pain, bloating, gas, and loss of appetite), metallic taste in the mouth, vitamin B12 deficiency, hypoglycemia, and, in rare cases, lactic acidosis—a condition characterized by the buildup of lactic acid leading to a very low pH level in the bloodstream.

Despite these potential side effects, the majority of users do not experience them. In this blog, I will discuss my personal experience with metformin, highlighting why I take it despite not being diabetic, prediabetic, or insulin resistant. My primary motivation is its potential for longevity. This interest was sparked by David Sinclair's book "Lifespan," which outlines the benefits of metformin and why he has taken it for years. Inspired, I conducted my own research and consulted with my primary care physician, who was also familiar with Sinclair's work. With his endorsement, I began taking metformin, and we have both observed its effects for longevity purposes.

The decision to take metformin was based on weighing the pros and cons, considering the minimal side effects against the potential benefits. Life is about making informed decisions, and nothing is strictly black or white. As new information becomes available, it's crucial to reassess and adjust our choices accordingly.

Let's explore how metformin works. It activates AMP-activated protein kinase (AMPK), a crucial enzyme for cellular energy homeostasis. This activation occurs in response to low energy states within cells, leading to various metabolic adjustments that can contribute to longevity and healthspan. By improving insulin sensitivity, metformin helps the body use insulin more effectively, playing a key role in managing glucose levels and insulin.

Metformin and Its Broader Benefits: Beyond Blood Sugar Control

Metformin reduces the body's insulin requirements, managing blood sugar levels more efficiently. For me, the improvement in insulin sensitivity stands out as the medication's most significant benefit. While achieving these health milestones naturally is ideal, metformin acts as a valuable adjunct. To me, this is its foremost advantage.

Inflammation Reduction: A Key to Combating Chronic Diseases

Inflammation is a root cause of many metabolic and other diseases. By potentially reducing inflammation, metformin could diminish the risk of these conditions. It accomplishes this by inhibiting the activation of B cells, key regulators in the inflammatory response. Without delving too deeply into the technicalities, it's sufficient to understand that metformin can decrease the production of pro-inflammatory cytokines, thereby lessening overall inflammation in the body and, consequently, the chronic diseases associated with it.

Oxidative Stress and Its Mitigation

Another benefit of metformin is its ability to reduce oxidative stress, achieved by activating AMP-activated protein kinase (AMPK). This activation enhances cellular energy efficiency and reduces the production of reactive oxygen species (ROS), thereby improving mitochondrial function and increasing the expression of antioxidants. As antioxidants neutralize free radicals (which contain one unpaired electron), metformin's role in increasing antioxidant expression ultimately helps reduce oxidative stress, contributing to its potential longevity-enhancing properties.

The TAME Trial: A Glimpse into the Future

The potential benefits of metformin, particularly in terms of longevity, remain a topic of keen interest. The Targeting Aging with Metformin (TAME) trial, a six-year study nearing its conclusion, aims to provide concrete evidence of metformin's effects on longevity. Should the study confirm positive effects, we might witness a surge in interest in this medication.

I'm currently taking metformin in moderation—500 mg not daily, but two to three times a week. On days of intense exercise, I abstain from taking it to avoid any potential imbalance in lactic acid and pH levels, even though hydration and electrolyte replenishment could counteract these effects. I've never encountered issues with lactic acid buildup but prefer a cautious approach.

Awaiting Results, with Caution and Optimism

The TAME trial focuses on non-diabetic individuals aged 65 to 75, exploring metformin's impact on age-related conditions such as heart disease, stroke, cancer, dementia, and overall mortality. This research could redefine metformin not merely as a diabetes medication but as a significant contributor to healthspan and lifespan extension.

In conclusion, my journey with metformin has been informative, revealing its numerous potential benefits alongside its side effects. I've shared how I was introduced to this medication, its advantages, and my personal regimen, highlighting upcoming studies that could further cement its role in enhancing health and longevity. Especially for individuals with diabetes, prediabetes, or insulin resistance, metformin offers promising benefits beyond glucose control, potentially reducing overall mortality and disease risk.

For everyone else, like myself, I advocate for a cautious approach—lower doses and less frequent use—until more definitive study results are available. At that point, I may adjust my usage based on new evidence and laboratory tests. Hopefully, this overview has been enlightening. As always, before considering any medication, it's crucial to educate yourself, consult healthcare professionals, and remember that in the United States, metformin requires a prescription. Engaging in an informed discussion with your healthcare provider is essential for making a mutual decision on its use.