Metformin: Difference between revisions

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== Introduction ==
== Introduction ==
Metformin, FDA-approved in 1994, is an antidiabetic agent used in type 2 diabetes mellitus. It is the drug of choice for patients with type-2 diabetes mellitus. The drug is very safe, is cardioprotective, and enables weight loss. Metformin comes in both immediate-release and extended-release and is available in several combination products with other antidiabetic agents.
[[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>.


Typically at diagnosis of type 2 diabetes, lifestyle management such as diet and exercise are recommended. Metformin is often used as monotherapy or in combination when diet and exercise are not effective at lowering hyperglycemia. According to the American Diabetes Association (ADA), metformin is the preferred first-line agent in patients with type-2 diabetes mellitus in adults and children ten years and older. <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>
* 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>
 
== 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" />


== Administration ==
== 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.  
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" />  
 
* Recommendations are to take metformin at the same time every day.
* Extended-release tablets are typically taken once daily with an evening meal and should be swallowed with a full glass of water.<ref name=":0" />


== Adverse Effects ==
== Adverse Effects ==
Metformin is generally regarded as safe and well-tolerated.  
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.  


* Gastrointestinal side effects, including diarrhea, nausea, and vomiting, are very common and typically occur in up to 30% of patients taking metformin.  
# 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.  
* Occurring less frequently, some patients experience chest discomfort, headache, diaphoresis, hypoglycemia, weakness, and rhinitis.
# Over time, metformin may block vitamin [[Vitamin B12 Deficiency|B12]] absorption in the body. Supplementation of vitamin B12 may be necessary<ref name=":0" />
* Decreased vitamin B12 levels are associated with long-term metformin and should be monitored, particularly in anemic or peripheral neuropathy patients. Supplementation of vitamin B12 may be necessary
# 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" />


While being one of the safest options in the biguanide class, metformin consumers may still experience serious side effects.
The consumption of certain items which may increase metformin’s side effect profile. Substances include:  
 
* Lactic acidosis, a rare but dangerous side-effect experienced, may present with confusion, lethargy, stupor, shallow breathing, hypotension, nausea and vomiting<ref name=":1">Company, B.-M. S. (n.d.). ''GLUCOPHAGE.'' Priceton: Bristol-Myers Squibb Company.  </ref>.
* 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>
 
Those taking metformin should be wary of the consumption of certain items which may increase metformin’s side effect profile. Substances that should be cautioned include:  


* Alcohol, which increases the risk of lactic acidosis
* Alcohol, which increases the risk of lactic acidosis
* The use of amiloride, digoxin, and morphine, because of their competition for elimination pathways
* The use of amiloride, [[Glycosides and Congestive Heart Failure|digoxin]], and morphine, because of their competition for elimination pathways
* Cimetidine and furosemide which increase metformin’s effect.<ref name=":1" />
* 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>
 
== Education ==
All interprofessional healthcare team members, including clinicians, physiotherapists, nurses, and pharmacists, who look after patients with diabetes mellitus, should be familiar with metformin. Importantly, the drug is relatively cheap. At the same time, the clinicians should encourage patients with diabetes mellitus to discontinue smoking, eat healthily, and participate in regular exercise. While it is a safe and well-tolerated drug, the interprofessional team still needs to monitor its use, be aware of contraindications and interactions


Therapists must educate the patient on  
== 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


* Monitoring their glucose levels.  
* 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>.
* 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>.


== Anti-ageing ==
== Anti Ageing Potential ==
In recent years, metformin, a widely used hypoglycemic drug, 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.  
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.


== Back to [[Pharmacological management of Diabetes Mellitus|Pharmacological Management of Diabetes Mellitus]]==
== Back to [[Pharmacological Management of Diabetes Mellitus]]==


== References  ==
== References  ==


<references />
<references />
[[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