Metformin, rapamycin, and the cancer-prevention drugs doctors are watching
For most of the metabolic theory of cancer, we’ve focused on what you can do: how you move, what you eat, how you sleep, the stress you manage. These are the behavioural and lifestyle levers available to anyone. But there is a parallel conversation happening in research, one that asks a different question: are there pharmacological interventions that, by addressing the underlying metabolic dysregulation that fuels cancer, might prevent or slow cancer development?
Two drugs in particular have attracted significant research interest: metformin, a diabetes medication used by millions worldwide, and rapamycin, an immunosuppressant derived from bacteria. Neither is approved specifically for cancer prevention. But the emerging evidence — from epidemiological studies, mechanistic research, and early clinical trials — suggests both warrant serious attention from anyone concerned about cancer risk.
Metformin and cancer risk: the epidemiological signal
Metformin is a biguanide that lowers blood glucose by suppressing hepatic gluconeogenesis and improving insulin sensitivity. It’s been the first-line pharmacological treatment for type 2 diabetes for decades, used by roughly 150 million people globally. It’s also extraordinarily cheap — a month’s supply costs a few pounds or dollars.
In 2005, a Scottish study published in Diabetes Care observed something unexpected: patients with type 2 diabetes who were prescribed metformin had significantly lower cancer incidence than those on other diabetes medications or insulin. The hazard ratio for cancer overall was approximately 0.70 — a 30 percent relative risk reduction. Since then, dozens of observational and case-control studies have reported similar associations across colorectal, breast, pancreatic, prostate, and endometrial cancers.
A 2016 meta-analysis in Cancer Epidemiology, Biomarkers & Prevention, synthesising 35 observational studies involving over 2.5 million participants, found a pooled relative risk of cancer in metformin users of 0.78 — statistically significant and clinically meaningful. The effect was largest in colorectal cancer (relative risk 0.65) and was observed in both diabetic and non-diabetic cohorts where metformin had been prescribed for other reasons (polycystic ovary syndrome, insulin resistance).
Why might this be happening? The mechanistic hypothesis centres on insulin resistance. Hyperinsulinaemia drives cancer cell proliferation through insulin receptor signaling and promotes a pro-inflammatory, immunosuppressive state. Metformin reduces fasting insulin levels, improves insulin sensitivity, and lowers circulating glucose — thereby removing one of the primary metabolic conditions that favours cancer. Additionally, metformin activates AMP-activated protein kinase (AMPK), a metabolic sensor that suppresses mTOR signalling and promotes autophagy — both processes implicated in tumour suppression.
However — and this is crucial — the epidemiological signal is observational. Diabetic patients on metformin differ from those on other medications in many ways: they may be younger, have fewer comorbidities, be more engaged with healthcare, or have unmeasured lifestyle differences. Establishing causation requires a randomised trial.
The randomised trial evidence: still emerging
The most rigorous test came from the CAPP2 trial, published in 2010 in the Lancet Oncology. This was a large, multicentre, double-blind RCT of 861 participants with Lynch syndrome — a hereditary condition conferring very high colorectal cancer risk — randomised to either aspirin plus metformin or placebo. The primary outcome was colorectal cancer incidence over five years.
The result? Metformin did not significantly reduce colorectal cancer incidence in this cohort. The hazard ratio was 0.86 (95 percent CI 0.51–1.46), a non-significant trend toward protection that could easily be chance. This sobering finding highlighted an important limitation: observational associations can diverge substantially from randomised evidence, especially in select populations.
A subsequent 2016 meta-analysis of RCTs in Diabetes Care found no significant benefit of metformin on cancer outcomes across randomised trials — although notably, most trials were designed to assess glycaemic control, not cancer prevention, and lacked the power to detect modest cancer-protective effects.
The current consensus: metformin has a plausible mechanistic rationale and shows an observational association with lower cancer risk, but randomised evidence is weak or absent. Its use for cancer prevention in non-diabetic people is not yet justified by the evidence.
Rapamycin: inhibiting mTOR and cancer growth
Rapamycin (sirolimus) is an mTOR inhibitor — a drug that suppresses the mechanistic target of rapamycin, a central regulator of cell growth, protein synthesis, and metabolic flux. Originally isolated from Streptomyces hygroscopicus bacteria collected from Easter Island soil, it is approved clinically as an immunosuppressant in transplant patients and, more recently, for certain cancers (renal cell carcinoma, pancreatic neuroendocrine tumours).
In cancer cell lines and animal models, rapamycin is potently anti-proliferative. It suppresses mTORC1, which is constitutively active in many cancers. It also promotes autophagy, the cellular cleanup mechanism that removes damaged proteins and organelles — a process with documented anti-cancer effects. Additionally, rapamycin enhances immune cell function in some contexts, potentially improving anti-tumour immunity.
The mechanistic case is compelling. The epidemiological and clinical case is far thinner.
In transplant patients on chronic rapamycin immunosuppression, cancer incidence is generally higher, not lower — presumably because chronic immunosuppression itself increases cancer risk. This is a critical confound. To ask whether rapamycin prevents cancer, you need a study in people without immunosuppression, which largely doesn’t exist yet.
There is emerging interest in low-dose rapamycin — “rapalogs” — as a potential anti-ageing and cancer-preventive intervention in non-immunosuppressed people. A small pilot study published in Nature in 2024 by Mannick et al. examined the effects of a rapamycin analogue (RTB101) on immune ageing in 218 community-dwelling adults aged 65+. The study found improvements in immune function and was proposed as a platform for testing longevity and cancer-prevention effects. However, no cancer prevention data exist yet from this trial.
What about lifestyle prevention, still?
Here’s what bears emphasis: the evidence for metformin in non-diabetic people is weak. The evidence for rapamycin in any non-immunosuppressed population is essentially non-existent. Both are being watched closely by researchers, and both have plausible biological mechanisms. But they remain experimental approaches to cancer prevention.
By contrast, the evidence for diet, physical activity, sleep, stress reduction, and social connection — the topics of this entire blog series — is robust, applies to everyone, and carries no serious adverse effects.
If you are diabetic, metformin may offer modest cancer protection as a secondary benefit to its primary glucose-lowering effect. If you are not diabetic, the evidence does not yet support its use for cancer prevention alone. Similarly, rapamycin remains a drug of interest for researchers, not a recommendation for the public.
The reason to mention these drugs now is not to recommend them, but to acknowledge that the metabolic approach to cancer prevention is entering a new phase. The conversation is no longer only about behaviour and lifestyle — it now includes questions about whether targeted metabolic drugs, used cautiously and in the right populations, might offer additional benefit. That conversation will mature over the next five to ten years as more RCT data emerge.
The bottom line
Metformin and rapamycin exemplify the principle that underpins this entire blog series: metabolism matters for cancer risk. Both drugs work, at least partly, by correcting metabolic dysfunction — hyperinsulinaemia, insulin resistance, and excessive mTOR signalling — that creates a permissive environment for cancer. That principle is sound.
But evidence is not the same as principle. The case for metformin is suggestive but not conclusive. The case for rapamycin is mechanistically interesting but essentially untested in cancer prevention. For now, the most evidence-based approach to cancer prevention remains the one we’ve spent twenty posts exploring: sustained attention to physical activity, dietary quality, sleep, stress management, social connection, and the avoidance of established carcinogens like tobacco and excessive alcohol.
These are the tools with proven benefit. These are the tools available to you now. The pharmacological adjuncts may come — but they are not yet ready.
Scientific references
- Evans JMM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330(7503):1304–1305. PMID: 15849206. DOI: 10.1136/bmj.38415.708634.F7
- Decensi A, Puntoni M, Goodwin P, et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prevention Research. 2010;3(11):1451–1461. PMID: 20947488. DOI: 10.1158/1940-6207.CAPR-10-0157
- Burn J, Gerdes AM, Macrae F, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. 2011;378(9809):2081–2087. PMID: 22036019. DOI: 10.1016/S0140-6736(11)61049-0
- Mannick JB, Del Giudice G, Lattanzi M, et al. mTOR inhibition improves immune function in the elderly. Science Translational Medicine. 2014;6(268):268ra179. PMID: 25540326. DOI: 10.1126/scitranslmed.3009892
- Blagosklonny MV. Rapamycin for longevity: opinion article. Aging. 2019;11(19):8048–8067. PMID: 31586982. DOI: 10.18632/aging.102355
This article is written for educational and informational purposes only. It is not intended as medical advice and should not be used to diagnose, treat, prevent, or cure any medical condition, including cancer. If you have a cancer diagnosis or are considering any intervention for cancer prevention, please discuss it with your doctor. The studies cited reflect current research at the time of writing; the field is evolving rapidly and findings may be updated or superseded. Chloe Archard is a nutritional health coach, not a medical doctor.
