Metformin: Difference between revisions

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== Introduction ==
== Introduction ==
[[File:Metformin 500mg Tablets.jpeg|right|frameless]]
Metformin is an antidiabetic agent used in [[Diabetes Mellitus Type 2|type 2 diabetes]]. Metformin comes in both immediate-release and extended-release and is used in several combination products with other antidiabetic agents. Metformin also has several off-label-approved indications, including [[gestational diabetes]], management of antipsychotic-induced weight gain, type 2 diabetes prevention, and the treatment and prevention of [[Polycystic Ovarian Syndrome|polycystic ovary syndrome]] (PCOS). Today, metformin is the only ADA-recommended antidiabetic for pre-diabetes. Possible potential indications include antiaging, anticancer, and neuroprotective effects<ref name=":3">Corcoran C, Jacobs TF. [https://www.ncbi.nlm.nih.gov/books/NBK518983/ Metformin]. InStatPearls [Internet] 2021 Jul 19. StatPearls Publishing. Available:https://www.ncbi.nlm.nih.gov/books/NBK518983/ (accessed 9.4.2022)</ref>.


* Metformin is on the World Health Organisation’s List of Essential Medicines needed for a basic health care system.<ref name=":2">The Conversation Weekly Dose: metformin, the diabetes drug developed from French lilac Available:https://theconversation.com/weekly-dose-metformin-the-diabetes-drug-developed-from-french-lilac-64430 (accessed25.9.2021)</ref>
* In Australia, approximately two-thirds of patients with type 2 diabetes are prescribed metformin, either alone or in combination with other pills, or with insulin injections.<ref name=":0">Corcoran C, Jacobs TF. Metformin, in StatPearls. Treasure Island (FL). 2019.Available: https://www.ncbi.nlm.nih.gov/books/NBK518983/ (accessed 25.9.2021)</ref>


In the control of type 2 diabetes, metformin, a relatively safe compound from the drug class of the biguanides, is usually the first drug utilized <ref name=":0">Rena, G., Pearson, E. R., & Sakamoto, K. (2013). Molecular mechanism of action of metformin: old or new insights?. ''Diabetologia'', ''56''(9), 1898-1906.</ref>. Its mechanism of action is widely accepted to work by inhibiting the mitochondrial complex 1 in hepatic cells, thereby reducing gluconeogenesis<ref name=":0" />. This mechanism helps in preventing hyperglycemia and maintenance of blood glucose levels by reducing the intrinsic release of glucose into the bloodstream.
== Action ==
Metformin reduces [[blood]] glucose levels by decreasing glucose production in the [[Liver Disease|liver,]] decreasing intestinal absorption, and increasing [[insulin]] sensitivity.Metformin decreases both basal and postprandial blood glucose.<ref name=":0" /> Metformin is considered weight neutral with the potential for modest weight loss. It is also unlikely to cause [[hypoglycemia]] and may be potentially cardioprotective.<ref name=":3" />


Metformin is frequently prescribed orally for adults starting at 500 mg, incrementally increasing dosage by 500 mg every week, with a maximum dose of 2,000 mg per day<ref name=":1">Company, B.-M. S. (n.d.). ''GLUCOPHAGE.'' Priceton: Bristol-Myers Squibb Company.  </ref>. If an individual requires higher doses, more than 2,000 mg, metformin will need to be administered 3 times per day, not exceeding 2,550 mg<ref name=":1" />. Children under 10 years old may also start at 500 mg, and increase by 500 mg weekly, however, their dosages must be administered twice per day, not exceeding 2,000 mg per day<ref name=":1" />.
== Administration ==
Metformin is an oral medication typically dosed from 500 to 2550 mg per day and administered with a meal to decrease GI upset. The daily dose is often titrated weekly in increments of 500 mg or 850 mg to reduce this risk. Depending on the form, it is taken once to three times daily.<ref name=":0" />  


After oral administration metformin is absorbed at a rate of 50-60% via intestinal plasma membrane monoamine transporters (PMAT), hepatic OCT1 and OCT3 transporters, and renal OCT2 transporters <ref name=":0" />. Metformin has a relatively long half-life of 5 hours because of its exclusive elimination through the kidneys, and the absence of biotransformation <ref>Madiraju, A. K., Qiu, Y., Perry, R. J., Rahimi, Y., Zhang, X. M., Zhang, D., ... & Casals, G. (2018). Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. ''Nature medicine'', 1.</ref>. 
== Adverse Effects ==
Metformin does not cause excessive hypoglycemia, which is an advantage over some other diabetes medications. It also doesn't cause weight gain, and it has benefits for some cardiovascular risk factors. It may even help with weight loss and lowering cholesterol.  


While being one of the safest options in the biguanide class, metformin consumers may still experience serious side effects. Therapists should be mindful of the following adverse events and the signs and symptoms that are associated with them. Lactic acidosis, a rare but dangerous side-effect experienced, may present with confusion, lethargy, stupor, shallow breathing, hypotension, nausea and vomiting<ref name=":1" />. Hypoglycemia may display as anxiety, restlessness, paresthesia, cold sweat, confusion, headache, instability, and irritability<ref>''Low Blood Glucose (Hypoglycemia)''. (2016, August). Retrieved from National Institute of Diabetes and Digestive and Kidney Diseases: <nowiki>https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/low-blood-glucose-hypoglycemia</nowiki>    </ref>. While vitamin B deficiency may be seen with neural signs (confusion, paresthesias, and agitation), cardiovascular arrhythmias, pins and needles sensation and skin lesions<ref>Healton, E. B., Savage, D. G., Brust, J. C., Garrett, T. J., & Lindenbaum, J. (1991). Neurologic aspects of cobalamin deficiency. ''Medicine'', ''70''(4), 229-245.</ref>. Along with these signs, therapists should always monitor blood pressure, which could be an indication of diabetes mismanagement<ref>Adler, A. I., Stratton, I. M., Neil, H. A. W., Yudkin, J. S., Matthews, D. R., Cull, C. A., ... & Holman, R. R. (2000). Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. ''Bmj'', ''321''(7258), 412-419.    </ref>. If symptoms are present and can’t be managed or brought under control, patients must be immediately referred to their physician.
# Metformin can cause nausea, upset stomach, and diarrhea, particularly when you first start taking it. Typically occur in up to 30% of patients taking metformin.
# Over time, metformin may block vitamin [[Vitamin B12 Deficiency|B12]] absorption in the body. Supplementation of vitamin B12 may be necessary<ref name=":0" />
# People with [[Chronic Kidney Disease|severe kidney impairment]] or [[Heart Failure|heart failure]] should not take metformin since in rare cases it can cause lactic acidosis. The risk is very low (around one in 30,000 people taking metformin) but the condition can be fatal.<ref>Very Well Health Metformin Available:https://www.verywellhealth.com/biguanides-diabetes-medications-1087355 (accessed 9.4.2022)</ref><ref name=":2" />


Those taking metformin should be wary of the consumption of certain items which may increase metformin’s side effect profile. The main substances that should be cautioned are alcohol, which increases the risk of lactic acidosis, the use of amiloride, digoxin, and morphine, because of their competition for elimination pathways and cimetidine and furosemide which increase metformin’s effect.<ref name=":1" />
The consumption of certain items which may increase metformin’s side effect profile. Substances include:  


Education is also is extremely important when working with a patient taking metformin. Therapists must educate the patient on their role in monitoring their glucose levels. They should be reminded to eat before therapy or physical activity, to avoid hypoglycemia<ref>''Type 2 diabetes''. (2018, September 15). Retrieved from Mayo Clinic: <nowiki>https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/diagnosis-treatment/drc-20351199</nowiki>       </ref>. They must monitor for changes and signs and symptoms of hyperglycemia, hypoglycemia, lactic acidosis, vitamin B deficiencies, and gastrointestinal discomfort. Patients must also be counseled on proper administration, and storage of metformin at room temperature, avoiding extreme temperatures and light<ref>''Metformin''. (2018, March 15). Retrieved from Medline Plus:https://medlineplus.gov/druginfo/meds/a696005.html (DiaBeta (glyburide) Tablets USP 1.25, 2.5 and 5 mg, 2009)</ref>. Abnormalities, or apprehensions must be reported and discussed with primary healthcare provider so dosage can be modified or patient switched to a different medication.
* Alcohol, which increases the risk of lactic acidosis
* The use of amiloride, [[Glycosides and Congestive Heart Failure|digoxin]], and morphine, because of their competition for elimination pathways
* Cimetidine and [[Diuretics|furosemide]] which increase metformin’s effect.<ref name=":1">Company, B.-M. S. (n.d.). ''GLUCOPHAGE.'' Priceton: Bristol-Myers Squibb Company. </ref>


== Back to [[Pharmacological management of Diabetes Mellitus|Pharmacological Management of Diabetes Mellitus]]==
== Physiotherapy ==
Physiotherapists should encourage patients with diabetes mellitus to [[Smoking Cessation and Brief Intervention|discontinue smoking]], eat healthily, and participate in regular [[Therapeutic Exercise|exercise]]. Therapists must educate the patient on


== Sub Heading 2 ==
* Monitoring their glucose levels.
* The need to eat before therapy or physical activity, to avoid hypoglycemia<ref>''Type 2 diabetes''. (2018, September 15). Retrieved from Mayo Clinic: <nowiki>https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/diagnosis-treatment/drc-20351199</nowiki>       </ref>.


== Sub Heading 3 ==
== Anti Ageing Potential ==
In recent years, metformin has attracted growing attention in the field of anti-aging research. Reportedly, numerous studies have indicated that metformin regulates aging-related pathways, possibly delaying the aging process by modulating these pathways. The elucidation of these anti-aging effects may provide insights into the age-retarding<ref>Hu D, Xie F, Xiao Y, Lu C, Zhong J, Huang D, Chen J, Wei J, Jiang Y, Zhong T. [https://pubmed.ncbi.nlm.nih.gov/33815878/ Metformin: A Potential Candidate for Targeting Aging Mechanisms]. Aging and disease. 2021 Apr;12(2):480. Available:https://pubmed.ncbi.nlm.nih.gov/33815878/ (accessed25.9.20210</ref> potential of metformin.


== Resources  ==
== Back to [[Pharmacological Management of Diabetes Mellitus]]==
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#numbered list
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== References  ==
== References  ==


<references />
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[[Category:Diabetes]]
[[Category:Pharmacology]]

Latest revision as of 18:19, 24 January 2023

Original Editor - Ashton Randolph

Top Contributors - Lucinda hampton, Ashton Randolph and Aminat Abolade  

Introduction[edit | edit source]

Metformin 500mg Tablets.jpeg

Metformin is an antidiabetic agent used in type 2 diabetes. Metformin comes in both immediate-release and extended-release and is used in several combination products with other antidiabetic agents. Metformin also has several off-label-approved indications, including gestational diabetes, management of antipsychotic-induced weight gain, type 2 diabetes prevention, and the treatment and prevention of polycystic ovary syndrome (PCOS). Today, metformin is the only ADA-recommended antidiabetic for pre-diabetes. Possible potential indications include antiaging, anticancer, and neuroprotective effects[1].

  • Metformin is on the World Health Organisation’s List of Essential Medicines needed for a basic health care system.[2]
  • In Australia, approximately two-thirds of patients with type 2 diabetes are prescribed metformin, either alone or in combination with other pills, or with insulin injections.[3]

Action[edit | edit source]

Metformin reduces blood glucose levels by decreasing glucose production in the liver, decreasing intestinal absorption, and increasing insulin sensitivity.Metformin decreases both basal and postprandial blood glucose.[3] Metformin is considered weight neutral with the potential for modest weight loss. It is also unlikely to cause hypoglycemia and may be potentially cardioprotective.[1]

Administration[edit | edit source]

Metformin is an oral medication typically dosed from 500 to 2550 mg per day and administered with a meal to decrease GI upset. The daily dose is often titrated weekly in increments of 500 mg or 850 mg to reduce this risk. Depending on the form, it is taken once to three times daily.[3]

Adverse Effects[edit | edit source]

Metformin does not cause excessive hypoglycemia, which is an advantage over some other diabetes medications. It also doesn't cause weight gain, and it has benefits for some cardiovascular risk factors. It may even help with weight loss and lowering cholesterol.

  1. Metformin can cause nausea, upset stomach, and diarrhea, particularly when you first start taking it. Typically occur in up to 30% of patients taking metformin.
  2. Over time, metformin may block vitamin B12 absorption in the body. Supplementation of vitamin B12 may be necessary[3]
  3. People with severe kidney impairment or heart failure should not take metformin since in rare cases it can cause lactic acidosis. The risk is very low (around one in 30,000 people taking metformin) but the condition can be fatal.[4][2]

The consumption of certain items which may increase metformin’s side effect profile. Substances include:

  • Alcohol, which increases the risk of lactic acidosis
  • The use of amiloride, digoxin, and morphine, because of their competition for elimination pathways
  • Cimetidine and furosemide which increase metformin’s effect.[5]

Physiotherapy[edit | edit source]

Physiotherapists should encourage patients with diabetes mellitus to discontinue smoking, eat healthily, and participate in regular exercise. Therapists must educate the patient on

  • Monitoring their glucose levels.
  • The need to eat before therapy or physical activity, to avoid hypoglycemia[6].

Anti Ageing Potential[edit | edit source]

In recent years, metformin has attracted growing attention in the field of anti-aging research. Reportedly, numerous studies have indicated that metformin regulates aging-related pathways, possibly delaying the aging process by modulating these pathways. The elucidation of these anti-aging effects may provide insights into the age-retarding[7] potential of metformin.

Back to Pharmacological Management of Diabetes Mellitus[edit | edit source]

References[edit | edit source]

  1. ↑ 1.0 1.1 Corcoran C, Jacobs TF. Metformin. InStatPearls [Internet] 2021 Jul 19. StatPearls Publishing. Available:https://www.ncbi.nlm.nih.gov/books/NBK518983/ (accessed 9.4.2022)
  2. ↑ 2.0 2.1 The Conversation Weekly Dose: metformin, the diabetes drug developed from French lilac Available:https://theconversation.com/weekly-dose-metformin-the-diabetes-drug-developed-from-french-lilac-64430 (accessed25.9.2021)
  3. ↑ 3.0 3.1 3.2 3.3 Corcoran C, Jacobs TF. Metformin, in StatPearls. Treasure Island (FL). 2019.Available: https://www.ncbi.nlm.nih.gov/books/NBK518983/ (accessed 25.9.2021)
  4. ↑ Very Well Health Metformin Available:https://www.verywellhealth.com/biguanides-diabetes-medications-1087355 (accessed 9.4.2022)
  5. ↑ Company, B.-M. S. (n.d.). GLUCOPHAGE. Priceton: Bristol-Myers Squibb Company.
  6. ↑ Type 2 diabetes. (2018, September 15). Retrieved from Mayo Clinic: https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/diagnosis-treatment/drc-20351199      
  7. ↑ Hu D, Xie F, Xiao Y, Lu C, Zhong J, Huang D, Chen J, Wei J, Jiang Y, Zhong T. Metformin: A Potential Candidate for Targeting Aging Mechanisms. Aging and disease. 2021 Apr;12(2):480. Available:https://pubmed.ncbi.nlm.nih.gov/33815878/ (accessed25.9.20210
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