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How does Metformin work?

Metformin is a prescription medication used to lower blood sugar levels in patients with diabetes – how does metformin work?

Diabetes Mellitus is a chronic, long-term disease associated with increased levels of blood sugar due to the body not producing enough insulin or being unable to adequately use the insulin it produces.

Insulin, the hormone secreted by the pancreas, is responsible for regulating the glucose levels in the blood. Metformin works by helping to reduce these blood glucose levels.

There are three main types of diabetes –  type 1 diabetes, type 2 diabetes, and gestational diabetes.

Type 2 diabetes is the most prevalent form of the disease, accounting for around 90 percent of diabetes patients.

In type 1 diabetes, the pancreas stops producing insulin, resulting in abnormally elevated blood sugar levels. This disease, also known as juvenile-onset diabetes, is first diagnosed during childhood or adolescence.

It is managed using injections or an insulin pump to deliver insulin to the body.

In type 2 diabetes, the cells in the body develop a resistance to the effects of insulin, preventing the glucose from transferring from the blood to the cells.

This leads to an increase in blood glucose levels and as the disorder progresses, the pancreas’ ability to produce insulin is reduced.

Type 2 diabetes is usually first identified during adulthood, however, in recent years it has started to become more common amongst younger populations.

The disease can be managed through a healthy diet and exercise alone or with medications to help maintain normal blood sugar levels, but how do medications like metformin actually work?

How does metformin work?

Metformin is an FDA-approved drug, primarily prescribed to treat type 2 diabetes.

Metformin is considered the preferred choice for the first line of treatment by medical professionals due to its safety profile, effectiveness, and low cost.

Several clinical studies have now also provided evidence that the drug can potentially work to lower the risk of coronary artery disease in type 2 diabetes patients. 

Metformin for diabetes

Metformin works by helping to reduce blood sugar levels to an acceptable range, primarily by decreasing glucose production by the liver.

By reducing the amount of glucose released by the liver, metformin works to reduce the amount of glucose found in the blood.

Metformin also passes through the intestines, where it acts to reduce the amount of sugar that is absorbed by the intestines, which results in less sugar being absorbed into the blood.

Metformin also works as an ‘insulin sensitizer’ – this means that it improves the body’s ability to effectively use insulin, leading to an increase in glucose uptake by the cells and lowering the amount of sugar in the blood.

While metformin does not cause hypoglycemia by itself, it can potentially lead to low blood sugar levels if taken in combination with other medications.

Metformin for polycystic ovary syndrome

The drug is also prescribed as a second line of treatment to women with polycystic ovary syndrome (PCOS), a condition in which the ovaries fail to release an egg, that is associated with infertility and hormonal imbalances.

In PCOS, metformin works to decrease insulin levels and stimulate ovulation.

Side effects of metformin

In comparison to several antidiabetic therapies, metformin is not associated with weight gain.

Several studies report that metformin decreased body weight in patients with type 2 diabetes, suggesting an association between the drug and weight loss.

According to some studies, metformin could potentially be administered to treat obese and overweight people without diabetes.

However, the use of the drug as a weight loss aid is not yet approved by governing health bodies.

Common side effects of metformin may include nausea, vomiting, upset stomach, diarrhea, or tiredness. Metformin is contraindicated in type 2 diabetes patients with chronic kidney disease, liver failure, or congestive heart failure.

This is because lactic acidosis –  lactate acid build-up in the blood – develops in patients with those conditions.

As the drug is removed from the body by the kidneys, it may accumulate in patients with impaired kidney function and possibly lead to precipitating lactic acidosis.

Types of metformin

Metformin can be prescribed in the form of standard (immediate-release) tablets, which is immediately released into the body and may need to be taken several times a day, depending on the dose prescribed by the doctor.

Extended-release tablets are also available, which are generally taken once in a given day.

The dosage as well as the type of tablet is usually determined by the patient’s doctor. The dose is likely adjusted over time based on the patient’s response to the drug.                                                                      

References

  1. Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci. 2014;19(7):658-664.
  2. Saeedi P, Petersohn I, Salpea P, et al. (2019). Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical Practice. doi: 10.1016/j.diabres.2019.107843
  3. Diabetes Mellitus (DM). (2019, May). Retrieved from https://www.merckmanuals.com/en-ca/home/hormonal-and-metabolic-disorders/diabetes-mellitus-dm-and-disorders-of-blood-sugar-metabolism/diabetes-mellitus-dm
  4. Rojas and Gomes: Metformin: an old but still the best treatment for type 2 diabetes. Diabetology & Metabolic Syndrome 2013 5:6.
  5. Luo, F., Das, A., Chen, J. et al. Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management. Cardiovasc Diabetol 18, 54 (2019). https://doi.org/10.1186/s12933-019-0860-y
  6. Lord Jonathan M, Flight Ingrid H K, Norman Robert J. Metformin in polycystic ovary syndrome: systematic review and meta-analysis BMJ 2003; 327:951. doi: 10.1136/bmj.327.7421.951
  7. Lee A, Morley JE. Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Obes Res 1998; 6: 47-53
  8. Golay, A. Metformin and body weight. Int J Obes 32, 61–72 (2008). https://doi.org/10.1038/sj.ijo.0803695
  9. Seifarth C, Schehler B, and Schneider HJ. (2013). Effectiveness of Metformin on Weight Loss in Non-Diabetic Individuals with Obesity. Exp Clin Endocrinol Diabetes. doi: 10.1055/s-0032-1327734
  10. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014; 312(24):2668-2675. doi:10.1001/jama.2014.15298
  11. Roumie CL, Chipman J, Min JY, et al. Association of Treatment With Metformin vs Sulfonylurea With Major Adverse Cardiovascular Events Among Patients With Diabetes and Reduced Kidney Function [published online ahead of print, 2019 Sep 19]. JAMA. 2019; 322(12):1-11. doi:10.1001/jama.2019.13206
  12. Misbin RI. (2004). The Phantom of Lactic Acidosis due to Metformin in Patients With Diabetes. Diabetes Care. doi: 10.2337/diacare.27.7.1791
  13. Metformin vs. Metformin ER: Which One Is Right for Me? Retrieved from https://www.goodrx.com/blog/metformin-vs-extended-release-metformin-pros-cons/
  14. How to Take Metformin Safely and Avoid Side Effects? Retrieved from https://www.goodrx.com/blog/how-to-take-metformin-safely-avoid-side-effects/
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