From: hubermanlab
Metformin is one of the most discussed drugs when it comes to its potential role in promoting longevity. During the Huberman Lab Podcast, Andrew Huberman and Dr. Peter Attia explored this topic extensively, diving into its history, mechanisms, and recent scientific research.
## What is Metformin?
Metformin is a medication primarily used to treat type 2 diabetes. It has been in use for several decades and is well known for its action in lowering blood sugar levels. The mechanism by which it operates involves the partial inhibition of mitochondrial complex I, which ultimately influences glucose production and glucose uptake in cells <a class="yt-timestamp" data-t="00:14:20">[00:14:20]</a>. This glucose management is crucial as it relates to the [[the_implications_of_energy_balance_on_health_and_weight_management | implications of energy balance]] and [[glp1_and_novel_medications_for_obesity_and_diabetes | novel approaches to metabolic disorders]] like obesity and diabetes.
## Early Research & Enthusiasm
The interest in Metformin's potential for extending lifespan was sparked significantly by a study conducted in 2014 by Banister et al. This study suggested a survival advantage in type 2 diabetics treated with Metformin compared to non-diabetic controls. It reported a 15% reduction in all-cause mortality over a 2.8-year period for those treated with Metformin <a class="yt-timestamp" data-t="00:35:00">[00:35:00]</a>.
### Geroprotection
Gero-protection is the concept of drugs that can protect against the biological aging process. Metformin's potential as a geroprotective agent lies in its role beyond glucose reduction. It may have additional effects on pathways associated with aging, such as reducing inflammation, impeding cellular senescence, and possibly inhibiting the mTOR pathway <a class="yt-timestamp" data-t="00:32:00">[00:32:00]</a>. These mechanisms align with [[interventions_to_slow_and_reverse_aging | interventions aimed at slowing and reversing aging]], which also often highlight the benefits of other [[supplements_and_their_impact_on_aging | supplements and dietary approaches]].
## Recent Findings and Re-Evaluation
Despite initial enthusiasm, recent studies have painted a more complex picture regarding Metformin and longevity. A Danish study by Keys and colleagues reassessed previous findings, focusing on all-cause mortality in diabetics under metformin treatment compared to non-diabetic controls <a class="yt-timestamp" data-t="01:30:00">[01:30:00]</a>. They reported no substantial survival benefit attributed to metformin when informative censoring was accounted for, challenging earlier conclusions of the Banister study <a class="yt-timestamp" data-t="01:08:00">[01:08:00]</a>.
## The TAME Trial
The upcoming TAME (Targeting Aging with Metformin) trial aims to provide more rigorous answers through a randomized controlled design, evaluating Metformin's effects on aging in a non-diabetic population. The trial will investigate whether the drug can serve as a bona fide geroprotective agent, separate from its glucose-lowering effects. Dr. Attia and Huberman both highlighted the significance of this trial in clarifying Metformin's role in longevity science <a class="yt-timestamp" data-t="01:27:00">[01:27:00]</a>.
## Conclusion: A Future Eye on Metformin
While metformin continues to be a critical medication for managing type 2 diabetes, its jury is still out regarding its utility as a tool for promoting longevity. The outcomes of forthcoming studies like the TAME trial will be crucial in determining whether metformin should be recommended beyond the bounds of its current applications <a class="yt-timestamp" data-t="01:30:00">[01:30:00]</a>.
In the meantime, researchers and clinicians like Dr. Attia advise maintaining a healthy lifestyle, regular exercise, and a nutritionally balanced diet as the most reliable methods for supporting longevity, in line with [[sciencebased_tools_for_fat_loss | evidence-based approaches to metabolic health]] and [[healthspan_and_longevity_strategies | strategies aimed at promoting healthspan and longevity]].