Metformin And Rapamycin: Signs Of (Extended) Life? How To Monetize?

by: Keith Williams


Intriguing results with Metformin beyond its dominant role in treating Type 2 diabetes.

Metformin being used for managing obesity.

Individual response to Metformin means it works well in some people and not at all in others.

Data manipulation and analysis companies moving into wellness programs; this could be how Metformin gets commercialized for wellness and life extension.

Initial trial using low dose of Rapamycin in dogs successful with statistically significantly improved heart function; human trials in progress.

For some time I've been tracking work on extending healthy lives and longevity, both from a scientific as well as an investment perspective. I indicated that there are a number of biotech startups that start out seeking to extend lifespan, but as a survival mechanism, end up choosing a disease that is more common with age and seeking to address that.

Life extending drugs Metformin and Rapamycin

Previously I've highlighted two drugs, Metformin and Rapamycin, developed for specific diseases, which might also extend lifespan as a side effect. Here is an update.


A good summary of the current status of Metformin has been published recently in Endocrine Today. This article describes the history of Metformin development, which has culminated in it being the recommended first-line drug for treating type 2 diabetes both in the US and worldwide. Because it is available as a generic and is cheap to manufacture, this drug could be used as a long term anti-aging drug (~$4 for 1 month supply).

Metformin has a number of positive health effects beyond its use in treating type 2 diabetes, including applications for treating some patients with obesity.

A six year placebo controlled study on 3000 elderly patients is underway to explore Metformin protection of age related disease occurrence. There are indications that Metformin may be protective against growth of cancer cells.

Of course prescribing Metformin as a life extending/quality of life drug is not an immediate prospect, although there have been some studies on a possible life extending action by Metformin.

The commercial prospects for this drug are limited as it is no longer patented and there seems to be limited opportunity to develop a proprietary formulation as it is easily administered as a daily tablet.

Since it is clear that Metformin doesn't work for everyone, perhaps the future for this kind of life extending drug might be to integrate its use into a wellness portfolio, with screening to see whether you are likely to benefit from the drug. This would mean packaging the drug in an informatics-based service business. Of course the benefits of Metformin need to be better clarified, but after that there needs to be a business model sorted out that doesn't rely on a patented position for the actual drug itself.

Management of patient data is now coming of age with cloud based electronic health records and data management with companies like Commvault (NASDAQ:CVLT). While these companies at present focus on integrating and making available a wide range of patient data, it is a logical step for these kinds of providers to assist health providers to mine and integrate data with a view to promoting wellness and reducing the cost of treatment after people get sick. In fact this approach is already emerging with companies like Nextgen Healthcare (a subsidiary of Quality Systems (QSII)). Investors looking for future investments in the healthcare area might keep an eye out for how companies like Commvault, and Nextgen are positioning themselves.

It isn't surprising that Craig Venter, who transformed the human genome project, is interested in this space with his company Human Longevity Inc. However, it has been argued that Human Longevity Inc is more a personalised medicine company than a longevity science company. So Human Longevity operates in a similar space to Nextgen Healthcare, except that a core feature of Venter's company is sequencing and annotating individual human genome data.


The Rapamycin story is different to Metformin as in the case of Rapamycin a number of big pharma companies have a patent position on variants of Rapamycin (Sirolimus). Novartis (NYSE:NVS) Everolimus and Pfizer (NYSE:PFE) Temsirolimus have been investigated for kidney cancer treatments, and also in combination with other drugs for exploring treatment of various cancers. Everolimus may also have fertility sparing attributes for women being treated with chemotherapeutic agents.

Abbott (NYSE:ABT) Zotarolimus and private company Elixir Medical Corp Novolimus (which is an active metabolite of Rapamycin (Sirolimus)) have been tested as a cardiac stent coating. Everolimus has also been used as a cardiac stent coating.

The above patented Rapamycin derivatives leave the way open for a more conventional drug development program for anti-aging and quality of life improvement. No doubt as part of consideration of Rapamycin derivatives for life extension applications, there are senior executives in big pharma trying to work out how this could play out.

Unlike the situation with Metformin where life extension possibilities are being identified through data mining of a large patient base who use Metformin, especially for Type 2 diabetes, in the case of Rapamycin, trials are being established to test low doses both in large animals (dogs) and humans to test more directly life extension and quality of life improvements.

Dog trials: The first phase of the Dog Aging Project has been completed; it involved a low dose of Rapamycin. There were 24 middle-aged dogs treated with placebo or Rapamycin in a trial in Seattle. The key findings, which will be published, were that there were no significant side effects of Rapamycin treatment and also that positive effects on heart function compared to controls were similar to results found after treating old mice. The trial involved a small number of animals and it produced limited, but encouraging results.

The second phase of the Dog Aging Project involves treating middle-aged dogs with low doses of Rapamycin (with a placebo control) for 3 -5 years to understand if Rapamycin does cause increased lifespan and a better elderly life. A number of age-related parameters will be assessed before, during and after the 3-5 year Rapamycin dosing period. Key parameters to be measured include cognitive function, heart function, immunity and cancer incidence. The geographical reach of the second phase trial will extend throughout the US and hopefully overseas. At the low doses used, no adverse effects of Rapamycin are expected.

Human trials: There are currently two human clinical trials assessing low doses of Rapamycin in progress.

One trial sponsored by The University of Texas Health Sciences Center at San Antonio and due for completion in June 2017, involves treating healthy (includes those with chronic disease whose disease is stable) aged volunteers aged 70-95 years with a daily dose of Rapamycin or placebo for 8 weeks. The primary endpoint involves scientific measurements of immune response and T-cell function. Secondary outcomes involve physical performance (grip strength, walking speed) and cognitive performance based on 3 different tests.

A second trial, sponsored by the Mayo Clinic, is a Phase 1 study that involves a small open label trial, which will be followed by a randomized trial involving exercise or exercise plus low dose of Rapamycin. Patients will be 60 years or older. It looks like this study was preceded by a pilot study measuring senescence markers and physical function in elderly patients undergoing cardiac rehabilitation. Rapamycin treatment showed some improvement of senescence markers and physical performance, but no improvement in frailty in the pilot study. The interesting point is that Rapamycin at a low dose unlikely to cause any adverse effects, is being taken seriously as a potential life extension/quality of life treatment. There are interesting developments in Rapamycin-like drugs that may have better potential as life extending drugs than Rapamycin itself.

The next developments here will be if big Pharma starts to do trials on their proprietary (patented) forms of Rapamycin.


As is often the case when new fields of medicine are opened up, the treatment, the drug pricing and the means of commercialisation are all unclear. It is a twist to contemplate taking a drug when you are well, but not without precedent as aspirin is often taken at low doses to prevent heart attack and stroke.

Here I've discussed two business models for old drugs that may have life extension/quality of life improvements. For Metformin I suggest that it could be incorporated in a wellness program. For Rapamycin a more traditional drug development route is possible. Watch this space.

Author's note: I am not a financial advisor. I look for innovation in biotech and try to understand how this may be monetized. If my commentary helps shape your perspective on biotech investment, please consider following me.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.