Metformin - Revision history

Andrea: Added category

2023-02-18T11:49:04Z

Added category

← Older revision		Revision as of 11:49, 18 February 2023
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	<references />		<references />
	[[Category:Drugs]]		[[Category:Drugs]]
			[[Category:Main list]]

Dmitry Dzhagarov: /* Mechanism */

2022-12-05T10:22:07Z

Mechanism

← Older revision		Revision as of 10:22, 5 December 2022
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	Metformin appears to mimic the processes involved with dietary restriction (DR) without the person having to restrict their diet.<ref>Lee, S.-H., & Min, K.-J. (2013). Caloric restriction and its mimetics. ''BMB Reports'', ''46''(4), 181–187. https://doi.org/10.5483/BMBRep.2013.46.4.033</ref> The exact mechanism of action of metformin remains unknown; it is often regarded as a 'dirty drug' because it targets a wide range of molecular pathways, and therefore exhibits many different effects. Some examples of its beneficial effects on human physiology in type 2 diabetes include its ability to reduce blood sugar levels, prevent accumulation of fat, and prevent hardening of the arteries.<ref>Wang, C., Liu, F., Yuan, Y., Wu, J., Wang, H., Zhang, L., ... & Ye, J. (2014). Metformin suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation. ''Clin Lab'', ''60''(6), 887-896.</ref><ref>Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. ''Diabetologia'', ''60''(9), 1577-1585.</ref> However, the caloric restriction (CR) mechanism of metformin has been called into question. One study has demonstrated that metformin-treated mice have impaired vision and spatial memory, in contrast with the known data for central nervous system benefits from CR.<ref>Thangthaeng, N., Rutledge, M., Wong, J. M., Vann, P. H., Forster, M. J., & Sumien, N. (2017). Metformin impairs spatial memory and visual acuity in old male mice. ''Aging and disease'', ''8''(1), 17.</ref>		Metformin appears to mimic the processes involved with dietary restriction (DR) without the person having to restrict their diet.<ref>Lee, S.-H., & Min, K.-J. (2013). Caloric restriction and its mimetics. ''BMB Reports'', ''46''(4), 181–187. https://doi.org/10.5483/BMBRep.2013.46.4.033</ref> The exact mechanism of action of metformin remains unknown; it is often regarded as a 'dirty drug' because it targets a wide range of molecular pathways, and therefore exhibits many different effects. Some examples of its beneficial effects on human physiology in type 2 diabetes include its ability to reduce blood sugar levels, prevent accumulation of fat, and prevent hardening of the arteries.<ref>Wang, C., Liu, F., Yuan, Y., Wu, J., Wang, H., Zhang, L., ... & Ye, J. (2014). Metformin suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation. ''Clin Lab'', ''60''(6), 887-896.</ref><ref>Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. ''Diabetologia'', ''60''(9), 1577-1585.</ref> However, the caloric restriction (CR) mechanism of metformin has been called into question. One study has demonstrated that metformin-treated mice have impaired vision and spatial memory, in contrast with the known data for central nervous system benefits from CR.<ref>Thangthaeng, N., Rutledge, M., Wong, J. M., Vann, P. H., Forster, M. J., & Sumien, N. (2017). Metformin impairs spatial memory and visual acuity in old male mice. ''Aging and disease'', ''8''(1), 17.</ref>

	Both type 1 and type 2 diabetes are regarded by aging biology researchers as diseases of accelerated aging. They lead to premature morbidity and mortality due to frailty, cancer, stroke, heart disease, dementia, kidney disease, diabetic retinopathy, peripheral neuropathy, and many other age-related diseases.		Both type 1 and type 2 diabetes are regarded by aging biology researchers as diseases of accelerated aging. They lead to premature morbidity and mortality due to [[frailty]], cancer, stroke, heart disease, dementia, kidney disease, diabetic retinopathy, peripheral neuropathy, and many other age-related diseases.

	As metformin is known to inhibit complex I of the mitochondria to activate AMPK and reduce mTOR signaling, which are molecular pathways associated with aging, there is some biological rationale for repurposing this drug to promote healthy aging in people without diabetes.<ref>Vial, G., Detaille, D., & Guigas, B. (2019). Role of mitochondria in the mechanism(s) of action of metformin. ''Frontiers in Endocrinology'', ''10''. https://doi.org/10.3389/fendo.2019.00294</ref> However, there is no clinical evidence that metformin can slow aging in healthy adult humans.		As metformin is known to inhibit complex I of the mitochondria to activate AMPK and reduce mTOR signaling, which are molecular pathways associated with aging, there is some biological rationale for repurposing this drug to promote healthy aging in people without diabetes.<ref>Vial, G., Detaille, D., & Guigas, B. (2019). Role of mitochondria in the mechanism(s) of action of metformin. ''Frontiers in Endocrinology'', ''10''. https://doi.org/10.3389/fendo.2019.00294</ref> However, there is no clinical evidence that metformin can slow aging in healthy adult humans.

	== The TAME Trial ==		== The TAME Trial ==

Andrea: /* Changed category to Drugs */

2022-06-19T10:20:50Z

Changed category to Drugs

← Older revision		Revision as of 10:20, 19 June 2022
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	== References ==		== References ==
	<references />		<references />
	[[Category:~~Longevity~~]]		[[Category:Drugs]]

Geroscientist: /* The TAME Trial */

2021-08-21T06:35:50Z

The TAME Trial

← Older revision		Revision as of 06:35, 21 August 2021
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	== Mechanism ==		== Mechanism ==
	Metformin appears to mimic the processes involved with dietary restriction without the person having to restrict their diet.<ref>Lee, S.-H., & Min, K.-J. (2013). Caloric restriction and its mimetics. ''BMB Reports'', ''46''(4), 181–187. https://doi.org/10.5483/BMBRep.2013.46.4.033</ref> The exact mechanism of action of metformin remains unknown; it is often regarded as a 'dirty drug' because it targets a wide range of molecular pathways, and therefore exhibits many different effects. Some examples of its beneficial effects on human physiology in type 2 diabetes include its ability to reduce blood sugar levels, prevent accumulation of fat, and prevent hardening of the arteries.<ref>Wang, C., Liu, F., Yuan, Y., Wu, J., Wang, H., Zhang, L., ... & Ye, J. (2014). Metformin suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation. ''Clin Lab'', ''60''(6), 887-896.</ref><ref>Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. ''Diabetologia'', ''60''(9), 1577-1585.</ref>		Metformin appears to mimic the processes involved with dietary restriction (DR) without the person having to restrict their diet.<ref>Lee, S.-H., & Min, K.-J. (2013). Caloric restriction and its mimetics. ''BMB Reports'', ''46''(4), 181–187. https://doi.org/10.5483/BMBRep.2013.46.4.033</ref> The exact mechanism of action of metformin remains unknown; it is often regarded as a 'dirty drug' because it targets a wide range of molecular pathways, and therefore exhibits many different effects. Some examples of its beneficial effects on human physiology in type 2 diabetes include its ability to reduce blood sugar levels, prevent accumulation of fat, and prevent hardening of the arteries.<ref>Wang, C., Liu, F., Yuan, Y., Wu, J., Wang, H., Zhang, L., ... & Ye, J. (2014). Metformin suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation. ''Clin Lab'', ''60''(6), 887-896.</ref><ref>Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. ''Diabetologia'', ''60''(9), 1577-1585.</ref> However, the caloric restriction (CR) mechanism of metformin has been called into question. One study has demonstrated that metformin-treated mice have impaired vision and spatial memory, in contrast with the known data for central nervous system benefits from CR.<ref>Thangthaeng, N., Rutledge, M., Wong, J. M., Vann, P. H., Forster, M. J., & Sumien, N. (2017). Metformin impairs spatial memory and visual acuity in old male mice. ''Aging and disease'', ''8''(1), 17.</ref>

	Both type 1 and type 2 diabetes are regarded by aging biology researchers as diseases of accelerated aging. They lead to premature morbidity and mortality due to frailty, cancer, stroke, heart disease, dementia, kidney disease, diabetic retinopathy, peripheral neuropathy, and many other age-related diseases.		Both type 1 and type 2 diabetes are regarded by aging biology researchers as diseases of accelerated aging. They lead to premature morbidity and mortality due to frailty, cancer, stroke, heart disease, dementia, kidney disease, diabetic retinopathy, peripheral neuropathy, and many other age-related diseases.

Geroscientist: /* Use in Medicine */

2021-08-21T06:32:30Z

Use in Medicine

← Older revision		Revision as of 06:32, 21 August 2021
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	=== Life extension in humans ===		=== Life extension in humans ===
	Research undertaken since metformin was approved by the FDA in 1994 has found that people who take metformin tend to be healthier than those who take another diabetes-related drug.<ref>Saraei, P., Asadi, I., Kakar, M. A., & Moradi-Kor, N. (2019). The beneficial effects of metformin on cancer prevention and therapy: A comprehensive review of recent advances. ''Cancer Management and Research'', ''11'', 3295–3313. https://doi.org/10.2147/CMAR.S200059</ref> They live longer, have fewer cardiovascular issues, get cancer less often, and tend to outlive other people with both diabetes and cancer on different medications.		Research undertaken since metformin was approved by the FDA in 1994 has found that people with type 2 diabetes who take metformin tend to be healthier than those who take another diabetes-related drug.<ref>Saraei, P., Asadi, I., Kakar, M. A., & Moradi-Kor, N. (2019). The beneficial effects of metformin on cancer prevention and therapy: A comprehensive review of recent advances. ''Cancer Management and Research'', ''11'', 3295–3313. https://doi.org/10.2147/CMAR.S200059</ref> They appear to live longer, have fewer cardiovascular issues, get cancer less often, and tend to outlive other people with both diabetes and cancer on different medications. Notably, this finding is based on observational studies that cannot account for confounding and other biases. Currently, there is no clinical evidence that metformin is beneficial for human aging.

	In a retrospective observational study of 90,400 subjects with diabetes who took metformin, compared to those taking another diabetes drug, and a matched control group of subjects without diabetes, it was found that metformin patients not only outlived the other subjects with diabetes but also lived longer than the subjects in the control group.<ref>Bannister, C. A., Holden, S. E., Jenkins-Jones, S., Morgan, C. L., Halcox, J. P., Schernthaner, G., Mukherjee, J., & Currie, C. J. (2014). 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, Obesity and Metabolism'', ''16''(11), 1165–1173. https://doi.org/https://doi.org/10.1111/dom.12354</ref> While there are various criticisms of the methodology of this paper, this has led scientists at the forefront of longevity to consider metformin as a drug with the potential to extend healthy lifespans – which could help people to not just live longer, but live more healthily for longer.		In a retrospective observational study of 90,400 subjects with diabetes who took metformin, compared to those taking another diabetes drug, and a matched control group of subjects without diabetes, it was found that metformin patients not only outlived the other subjects with diabetes but also lived longer than the subjects in the control group.<ref>Bannister, C. A., Holden, S. E., Jenkins-Jones, S., Morgan, C. L., Halcox, J. P., Schernthaner, G., Mukherjee, J., & Currie, C. J. (2014). 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, Obesity and Metabolism'', ''16''(11), 1165–1173. https://doi.org/https://doi.org/10.1111/dom.12354</ref> While there are various criticisms of the methodology of this paper, this has led scientists at the forefront of longevity to consider metformin as a drug with the potential to extend healthy lifespans – which could help people to not just live longer, but live more healthily for longer.

Bogdan at 15:13, 5 July 2021

2021-07-05T15:13:36Z

← Older revision		Revision as of 15:13, 5 July 2021
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	== References ==		== References ==
			<references />
			[[Category:Longevity]]

Geroscientist: /* The TAME Trial */

2021-06-29T12:27:49Z

The TAME Trial

← Older revision		Revision as of 12:27, 29 June 2021
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	== Side effects ==		== Side effects ==
	Common side effects (which affect 1 in 100 people) include feeling or being sick, stomach ache, loss of appetite and/or a metallic taste in the mouth.		Common side effects (which affect 1 in 100 people) include feeling or being sick, stomach ache, diarrhea, loss of appetite and/or a metallic taste in the mouth.

	Serious side effects are very rare and affect less than 1 in 10,000 people. These can include severe tiredness, a slow heart rate, liver problems, or a rash. It is also possible to have a serious allergic reaction (anaphylaxis) to metformin if one is allergic to its active ingredients.		Serious side effects are very rare and affect less than 1 in 10,000 people. These can include severe tiredness, a slow heart rate, liver problems, or a rash. One controversial adverse effect is related to lactic acidosis; a cochrane review of randomized trials published in 2010 showed that metformin is not associated with an increased risk for lactic acidosis, when prescribed under specified study conditions.<ref>Salpeter, S. R., Greyber, E., Pasternak, G. A., & Salpeter, E. E. (2010). Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. ''Cochrane database of systematic reviews'', (4).</ref> It is also possible to have a serious allergic reaction (anaphylaxis) to metformin if one is allergic to its active ingredients.

	== References ==		== References ==

Geroscientist: /* The TAME Trial */

2021-06-29T12:22:48Z

The TAME Trial

← Older revision		Revision as of 12:22, 29 June 2021
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	== Life extension effects ==		== Life extension effects ==
	=== Life extension in model organisms ===		=== Life extension in model organisms ===
	In animal trials, metformin has been found to extend the lifespan of roundworms, silkworms, mice, and rats.<ref>Lamming, D. W., Sabatini, D. M., & Baur, J. A. (2012). Pharmacologic means of extending lifespan. ''Journal of Clinical & Experimental Pathology'', ''Suppl 4''. https://doi.org/10.4172/2161-0681.S4-002</ref>		In animal trials, metformin has been found to extend the lifespan of roundworms, silkworms, mice, and rats.<ref>Lamming, D. W., Sabatini, D. M., & Baur, J. A. (2012). Pharmacologic means of extending lifespan. ''Journal of Clinical & Experimental Pathology'', ''Suppl 4''. https://doi.org/10.4172/2161-0681.S4-002</ref><ref>Song, J., Jiang, G., Zhang, J., Guo, J., Li, Z., Hao, K., ... & Dai, F. (2019). Metformin prolongs lifespan through remodeling the energy distribution strategy in silkworm, Bombyx mori. ''Aging (Albany NY)'', ''11''(1), 240.</ref>

	=== Life extension in humans ===		=== Life extension in humans ===

Geroscientist: /* Side effects */

2021-06-29T12:21:48Z

Side effects

← Older revision		Revision as of 12:21, 29 June 2021
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	== Life extension effects ==		== Life extension effects ==
	=== Life extension in model organisms ===		=== Life extension in model organisms ===
	In animal trials, metformin has been found to extend the lifespan of ~~worms~~, mice, and rats ~~from 5-50%~~.<ref>Lamming, D. W., Sabatini, D. M., & Baur, J. A. (2012). Pharmacologic means of extending lifespan. ''Journal of Clinical & Experimental Pathology'', ''Suppl 4''. https://doi.org/10.4172/2161-0681.S4-002</ref>		In animal trials, metformin has been found to extend the lifespan of roundworms, silkworms, mice, and rats.<ref>Lamming, D. W., Sabatini, D. M., & Baur, J. A. (2012). Pharmacologic means of extending lifespan. ''Journal of Clinical & Experimental Pathology'', ''Suppl 4''. https://doi.org/10.4172/2161-0681.S4-002</ref>

	=== Life extension in humans ===		=== Life extension in humans ===

Geroscientist: /* The TAME Trial */

2021-06-29T12:19:17Z

The TAME Trial

← Older revision		Revision as of 12:19, 29 June 2021
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	== Life extension effects ==		== Life extension effects ==
	=== Life extension in model organisms ===		=== Life extension in model organisms ===
	In animal trials, metformin has been found to extend the lifespan of worms, mice, ~~fruit flies~~ and ~~yeast~~ from 5-50%.<ref>Lamming, D. W., Sabatini, D. M., & Baur, J. A. (2012). Pharmacologic means of extending lifespan. ''Journal of Clinical & Experimental Pathology'', ''Suppl 4''. https://doi.org/10.4172/2161-0681.S4-002</ref>		In animal trials, metformin has been found to extend the lifespan of worms, mice, and rats from 5-50%.<ref>Lamming, D. W., Sabatini, D. M., & Baur, J. A. (2012). Pharmacologic means of extending lifespan. ''Journal of Clinical & Experimental Pathology'', ''Suppl 4''. https://doi.org/10.4172/2161-0681.S4-002</ref>

	=== Life extension in humans ===		=== Life extension in humans ===