In 2014, a published article indicated that people who took metformin, a frontline treatment for type 2 diabetes, may live longer than those who didn’t. The drug gained a large amount of popularity as a potential longevity drug in certain health-enthusiast circles.
However, a lot of recent research rejects that conclusion, showing that individuals who take metformin have no difference in various mortality outcomes. In other words, the drug works for treating type 2 diabetes, but it does nothing to increase your lifespan.
As I like doing, I will review the recent research and determine if there is any indication that metformin is a miracle drug for aging and health.
What is metformin?
Just for background, type 2 diabetes mellitus (or type 2 diabetes, T2DM) is a metabolic disorder that is characterized by high blood glucose with insulin resistance and relative insulin deficiency. In general, someone with T2DM produces low (or maybe even adequate) insulin levels, but various cells and organs become resistant to insulin, so cells don’t remove or store blood glucose.
Although the cause of T2DM is not completely understood, it results from a complex interaction between diet, obesity, genetics, age, and gender. Some of the causes of T2DM are under a person’s control, like diet and obesity, but many of the causal factors are not.
Metformin is used as a frontline medication to treat type 2 diabetes, first approved for use in the USA in 1994. Although its mechanism of action is not well understood, it appears to reduce gluconeogenesis (the production of glucose by the liver and other organs, which increases blood glucose levels), increase insulin sensitivity, and reduce appetite.
The research that claimed that metformin could increase lifespan did not adequately explain a biologically plausible mechanism that could account for such a result.
Recent metformin research
Several papers have been published over the past few years that seem to show that metformin has little effect on lowering the risk of mortality and increasing lifespan. Below is a quick review of some of the research on the drug, and their conclusions.
- In a paper published in December 2021 in Diabetes Care, researchers did a 21-year randomized controlled trial that found metformin didn’t reduce cancer, cardiovascular disease, or mortality rates in adults who were non-diabetic but at high risk for Type 2 diabetes. This paper convinced a lot of physicians who were touting metformin as the “fountain of youth” drug
- In a paper published on 13 December 2022 in the International Journal of Epidemiology, the researchers attempted to repeat the 2014 study that started this craze. Instead, they found the drug wasn’t associated with a lifespan equal to or better than that of the general population.
- In a systematic review and meta-analysis (considered at the top of the hierarchy of medical research) published on 8 July 2020 in BMJ Open Diabetes Research and Care, the researchers found that metformin use had no effect on the prevention of neurodegenerative diseases like Parkinson’s disease. In fact, metformin may be linked to a higher risk of Parkinson’s.
- However, there is still positive news about using metformin. In a paper published on 5 August 2021 in Frontiers in Endocrinology (Lausanne), the researchers concluded that “via its ability to reduce early mortality associated with various diseases, including diabetes, cardiovascular disease, cognitive decline, and cancer, metformin can improve healthspan thereby extending the period of life spent in good health.” This does not mean it is a miracle drug, but it can reduce mortality in treating certain diseases, specifically type 2 diabetes.
- In a paper published in 2018 in Current Medicinal Chemistry, the researchers concluded that metformin appeared to promote better organ function, increased physical resistance, disease resistance, and prolonged life expectancy.
Right now, the totality of research seems to not provide definitive evidence that metformin has any effect on aging or lowered mortality other than treating type 2 diabetes, which itself can lead to a shorter life and other poor medical outcomes that reduce lifespan.
However, I examined current or completed clinical trials involving metformin and aging, and there appear to be at least 10 that will try to answer whether the drug has an effect on long-term health outcomes. Clinical trials are what is required here — they may provide better evidence of the claim that metformin is a great drug for aging.
For the time being, I remain very skeptical of the research done so far. There are no large clinical trials that have shown the effects of the drug, and the studies that seem to be positive can’t determine if the positive effects are a result of treating or preventing type 2 diabetes rather than a mechanism that actually prevents aging.
Metformin is a relatively safe drug, so if some people use it in the hope that it will work, probably can do so safely. But for now, I’d say the evidence really doesn’t strongly support its effects. With the extensive clinical trials, maybe we will see some more definitive results in the future.
- Bannister CA, Holden SE, Jenkins-Jones S, Morgan CL, Halcox JP, Schernthaner G, Mukherjee J, Currie CJ. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab. 2014 Nov;16(11):1165-73. doi: 10.1111/dom.12354. Epub 2014 Jul 31. PMID: 25041462.
- Keys MT, Thinggaard M, Larsen LA, Pedersen DA, Hallas J, Christensen K. Reassessing the evidence of a survival advantage in Type 2 diabetes treated with metformin compared with controls without diabetes: a retrospective cohort study. Int J Epidemiol. 2022 Dec 13;51(6):1886-1898. doi: 10.1093/ije/dyac200. PMID: 36287641.
- Klimova B, Novotny M, Kuca K. Anti-Aging Drugs – Prospect of Longer Life? Curr Med Chem. 2018;25(17):1946-1953. doi: 10.2174/0929867325666171129215251. PMID: 29189123.
- Lee CG, Heckman-Stoddard B, Dabelea D, Gadde KM, Ehrmann D, Ford L, Prorok P, Boyko EJ, Pi-Sunyer X, Wallia A, Knowler WC, Crandall JP, Temprosa M; Diabetes Prevention Program Research Group; Diabetes Prevention Program Research Group:. Effect of Metformin and Lifestyle Interventions on Mortality in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care. 2021 Dec;44(12):2775-2782. doi: 10.2337/dc21-1046. Epub 2021 Oct 25. PMID: 34697033; PMCID: PMC8669534.
- Mohammed I, Hollenberg MD, Ding H, Triggle CR. A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan. Front Endocrinol (Lausanne). 2021 Aug 5;12:718942. doi: 10.3389/fendo.2021.718942. PMID: 34421827; PMCID: PMC8374068.
- Ping F, Jiang N, Li Y. Association between metformin and neurodegenerative diseases of observational studies: systematic review and meta-analysis. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001370. doi: 10.1136/bmjdrc-2020-001370. PMID: 32719079; PMCID: PMC7390234.
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