Sole biguanide agent in the US.

Available in short and sustained-release formulations.

Has the best benefit-risk profile for glycemic control, weight loss and safety.

Recommended as initial treatment for type 2 diabetes.

Metformin, compared with lifestyle modification alone, is associated with a 39% reduction in myocardial infarction and a 36% reduction in all-cause mortality in type 2 diabetes.

Works primarily by decreasing hepatic glucose output and a relatively minor effect on increasing insulin sensitivity.

Hepatic gluconeogenesis may be reduced by 75%.

It decreases the amount of blood sugar that the liver produces and that the intestines or stomach absorb.

Its pleitropic affects, include decreased inflammation, increase insulin and leptin sensitivity, and decreased hunger  and gherlin levels, especially with twice daily dosing.

Acts in the liver where it inhibits gluconeogenesis by blocking a mitochondrial redox shuttle.

It is an insulin sensitize and likely acts in the lumen through multiple mechanisms.

Metformin, taken with diet and exercise changes to prevent diabetes in people who are at high risk for becoming diabetic.

It is frequently used in patients with pre-diabetes, polycystic, ovary syndrome, and overweight/obesity to mitigate weight gain due to antipsychotic medications.

It increases the effects of insulin, and is termed an “insulin sensitizer”.

A biguanide, is the most widely used oral antidiabetic drug that is generally

Recommended for first-line medical treatment of type 2 diabetes.

Early initiation of metformin at the time of diagnosis, when glycosylated hemoglobin levels are not significantly elevated, has been associated with improved glycemic control over time and decreased long-term complications.

Metformin is believed to activate AMP-activated protein kinase (AMPK), a major cellular regulator of lipid and glucose metabolism.

Metformin has been shown to be highly effective at reducing the onset ofdiabetes by 31% in 3234 prediabetic adults over a period of 2.8 years in the DPP (Diabetes Prevention Program) study 72 and at reducing systemic inflammation.

Also suppresses the endogenous glucose production by the liver, which is mainly due to a reduction in the rate of gluconeogenesis and a small effect on glycogenolysis.

It activates the enzyme adenosine monophosphate kinase (AMPK) inhibiting enzymes involved in gluconeogenesis and glycogen synthesis in the liver while stimulating insulin signaling and glucose transport in muscles.

Metformin is believed to activate AMP-activated protein kinase (AMPK), a major cellular regulator of lipid and glucose metabolism.

Improves glycemic control without inducing hypoglycemia or weight gain.

Metformin has modulating effects on a pathway known to play a major role in lifespan extension.

Metformin also upregulates peroxisome proliferator–activated receptor gamma coactivator 1-alpha, a master regulator of mitochondrial function, and a transcription factor that controls antioxidant programs.

Because these molecules (AMPK, mammalian target of rapamycin, and peroxisome proliferator–activated receptor gamma coactivator 1-alpha) are interconnected through cellular signaling networks implicated in the modulation of the aging process, it has been postulated that metformin could slow aging and age-related diseases.

Metformin is believed to activate AMP-activated protein kinase (AMPK), a major cellular regulator of lipid and glucose metabolism. 

Metformin has modulating effects on a pathway known to play a major role in lifespan extension. 

Metformin also upregulates peroxisome proliferator–activated receptor gamma coactivator 1-alpha, a master regulator of mitochondrial function, and a transcription factor that controls antioxidant programs. 

Observational studies indicate that metformin reduces mortality and frailty.

Use associated with lower rate of atrial fibrillation.

Use associated with lower incidence of atrial fibrillation.

Use associated with lower fasting insulin concentrations.

One of the few drugs that shows a significant reduction of macrovascular events and diabetes related mortality.

Antioxidants have beneficial effects such as anticancer, antidiabetes and antiatherosclerosis properties.

It has been shown to reduce visceral adiposity and insulin resistance after 8 weeks of drug therapy.

Trade name Glucophage.

Use associated with weight loss.

Metformin is associated with approximately 3% weight loss in approximately 25 to 50% of participants achieve at least 5% weight loss.

Long-term use associated with anemia-6% higher risk of anemia for every cumulative yer of metformin exposure (Donnelly L).

Decreases HgbA1C by 1 to 2%.

As much as 88% of weight loss is body fat mass.

Primarily used for the treatment of type 2 diabetes mellitus, particularly in obese.patients.

Reduce diabetes mortality and complications by thirty percent compared to insulin, and chlorpropamide.

Reduces serum glucose level by several different mechanisms, notably through nonpancreatic mechanisms without increasing insulin secretion.

Drug use contraindicated in many patients with impaired kidney function because of concerns of lactic acidosis.

The occurrence of dehydration can increase the risk of lactic acidosis.

The elderly may be at greater risk for hypoglycemia or lactic acidosis.

Its pharmacokinetics are affected by pregnancy, related to the changes in renal filtration and net tubular transport.

A fetus is exposed to variable concentrations of metformin.

Infant exposure to metformin through the breast milk is low.

Has nephroprotective activity against nephrotoxic agents.

Use in patients with diabetes and advanced chronic kidney disease is associated with greater mortality risk.

Side effects include: Nausea, vomiting, stomach upset, diarrhea, weakness, or a metallic taste in the mouth may occur.

It usually does not cause hypoglycemia; however, low blood sugar may occur if this drug is used with other anti-diabetic drugs.

Hypoglycemia is more likely to occur with metforminn with heavy exercise, drinking large amounts of alcohol, or not consuming enough calories from food.

Previous data suggesting it should be contraindicated in patients with impaired kidney function, but more up-to-date information suggests that can be used cautiously in mild to moderate chronic kidney disease.

Use in patients with advanced chronic kidney disease reveals all cause mortality is significantly higher (and is dose-dependent) than in patients with chronic kidney disease in diabetics and non-users of metformin.

Patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin compared with a sulfonylurea is associated with a lower risk of major adverse cardiac events.

The presence of hyperinsulinemia has been noted in many patients with cardiac syndrome X, and metformin has been shown to improve vascular function and decrease myocardial ischemia in nondiabetic women with chest pain and angiographically normal coronary arteries.

Although renally cleared drug levels generally remain within the therapeutic range and lactate concentrations are not not substantially increased when used in patients with mild-moderate chronic kidney disease (estimated GFR 30-60 mils per minute per 1.73 m²) (Inzucchi SE et al).

Incidence of lactic acid doses in metformin users is approximately 3 per 100,000-person-years to 10 per 100,000 person years and is indistinguishable from the background rate in th overall population with diabetes.

Lactic acid levels do not increase in patients with normal renal function.

Recent studies suggest no increase in lactic acidosis with mild to moderate chronic kidney disease or congestive heart failure.

Major clinical effect is decreased fasting glucose levels..

Most patients have approximately 1.5 reduction in HbA1C.

Referred to as an antihyperglycemic agent rather than a hypogolycemic drug.

Incidence of associated hypoglycemia is low.

May modestly decrease triglycerides because of decreased very low density lipoprotein production.

Must be stopped 48 hours after intravenous contrast administration and restarted when normal renal function is documented to decrease the chance of lactic acidosis.

Lactic acidosis is the most severe adverse affect and is associated with older age, cardiac disease, the compensated congestive heart failure, renal insufficiency, chronic pulmonary disease, and hypoperfusion.

Can rarely cause lactic acidosis with risk related to sepsis, dehydration, excess alcohol intake liver insufficiency renal impairment and acute congestive heart failure.

Incidence of lactic acidosis very low, approximately 0.03 cases/1,000 patient- years with approximately 0.015 fatal cases/1,000 patient-years.

Lowers blood glucose levels by sensitizing the liver to the effects of insulin, thus suppressing hepatic glucose output.

Decreases the amount of glucose produced by the liver and reduces blood stream level and cellular uptake of insulin.

Improves peripheral insulin sensitivity so that it improves skeletal muscle glucose utilization.

In type 2 diabetics improves both basal and postprandial plasma glucose.

Metformin stimulates AMP-activated protein kinase and reduces hepatic glucose production.

It reduces insulin stimulation resulting in reduced activation of insulin receptors on cell membranes, triggering intracellular molecular effects such as down regulation of the RAS/RAF/MEK/ERK and P13K/AKT/mtor signaling pathways.

Upregulates AMP-activated protein kinase, a key molecule in glucose and insulin regulation and also an inhibitor of mTOR.

Activates AMP-activated protein kinase, a major sensor cellular energy levels and a key enzymes limiting growth during times of cellulitis stress.

Activated AMP protein kinase PX protein, cholesterol, and fatty acids synthesis and inhibits mTOR.

Reverses hyperinsulinemia, leading to the down regulation of insulin-like4 growth factors that can promote tumorogenesis by activating of the phosphatidylinositol 3 kinase/protein kinase B pathway.

Enhances phosphorylation of AMP-activated protein kinase,, inducing changes in the intracellular pathways, ALT is mitochondrial function and may result in improved systolic and diastolic function.

Observation studies of acute myocardial infarction and treatment with metformin is associated with lower peak CK levels, troponins and improve survival after STEMI in patients type 2 diabetes, compared with other anti-glycemic strategies.

Among patients without diabetes and who presented with a STEMI and undergo primary PCI, the use of metformin compared with placebo does not improve left ventricular ejection fraction after 4 months (Lexis CP et al.

Associated with a 31% reduction in diabetes compared to placebo in patients with impaied glucose tolerance (DDP Research Group).

Increases GLP-1 secretion and inhibits GLP-1 degradation.

Among obese adolescents with type one diabetes the addition of metformin to insulin does not improve glycemic control (Libman IM et al).

Lowers cholesterol, triglyceride, and reduces hyperinsulinemeia, improves insulin sensitivity, and assists with weight reduction.

Decreases overall mortality in overweight Type 2 diabetics.

The international Reduction of Atherothrombosis for Continued Health (REACH) Registry indicated that the use of metformin as a means of secondary prevention in diabetes was associated with a 24% reduction in all-cause mortality after two years follow-up.

In obese diabetic patients uses so Siri Siri 2% reduction in the diabetes-related endpoint, 42% reduction in diabetes related death, and 36% reduction in mortality (UKPDS).

In the above study patients receiving metformin had a 39 percent reduction in the risk of nonfatal MI.

Other studies on metformin have not shown improvement in microvascular with macrovascular morbidity or mortality.

Associated with lactic acidosis, anorexia, nausea and diarrhea.

May be associated with metallic taste, nausea, diarrhea, and abdominal pain.

Symptoms can be minimized by starting with a low dose and titrating slowly, dividing doses and taking the drug with food.

Decreased vitamin B12 levels have occurred in patients on long-term treatment and rarely has been associated with anemia.

Metformin, might reduce the absorption of vitamin B12, possibly through alterations in intestinal mobility, increased bacterial overgrowth, or alterations in the calcium-dependent uptake by ileal cells of the vitamin B12-intrinsic factor complex.

10%–30% of patients who take metformin have reduced vitamin B12 absorption.


Contraindicated: in patients older than 80 years unless normal creatinine is present, in patients with abnormal renal or hepatic function and in patients taking medications for congestive heart failure.

Improves ovarian function in polycystic ovarian syndrome.

In women with polycystic ovarian syndrome, it may make menstrual cycles more regular and increase fertility.

In a large review using 27 clinical trials found metformin was not associated with any increase in the number of live births; however, it improved ovulation rates, especially when it was used in combination with clomiphene in polycystic ovarian disease.

With polycystic ovary syndrome, it is a first choice because of positive effects on insulin resistance, hirsutism, anovulation and obesity.

Metformin improves endothelial function in women with PCOS and endothelial dysfunction independent of changes in glucose metabolism metabolism, dyslipidemia or presence of pre-diabetes.

Metformin has a direct effect on endothelial function in PCOS.

In conjunction with clomiphene citrate acts to increased ovulation and pregnancy rates in polycystic ovarian syndrome.

May reduce rate of spontaneous abortion rate.

Decreases free circulating testosterone through an effect on liver sex hormone binding globulin, modulates adrenal androgen production and decreases ovarian androgen production associated well.

Can improve hirsutism.

Crosses the placenta.

Utilization in gestational diabetes alone, or with supplemental insulin, not associated with increased perinatal complications compared to the use of insulin alone.


Observational studies indicate the outcomes for individuals with type two diabetes receiving Metformin while undergoing cancer treatment are improved.

Metformin reduces insulin signaling through the PIK3 and RAS pathways and activates AMPK, which inhibits downstream AKT/mTOR, impairing cancer cell growth.

There is strong evidence for a lack of benefit from metformin treatment in metabolically healthy individuals.

Use probably protects against liver cancer, lower risk for oral cancer, improves prognosis of pancreatic cancer in diabetic patients, increases response rate in melanoma treated tumors with BRAF mutations and chemotherapy agents.

The risk of pancreatic cancer in patients taking metformin is a 62% lower than in placebo group who did not use metformin.

While diabetic participants having sulfonylureas or insulin were found to have a 2.5-fold and 5-fold higher risk of pancreatic cancer, respectively, in comparison to placebo group.

Diabetic patients using metformin may have a lower the risk of cancer compared to those using other anti-diabetic drugs.

Has strong antiproliferative effects on colon, pancreatic, breast, ovarian, prostate and lung cancer cells.

Diabetes is a common disease that may occur throughout human life, and can increase the likelihood of the occurrence of various types of cancer, such as colon, rectum, pancreas and liver cancers, compared to non-diabetic patients.

Metformin inhibits mTOR activity by activating ATM (ataxia telangiectasia mutated) and LKB1 (liver kinase B1) and then adenosine monophosphate-activated kinase (AMPK), and thus prevents protein synthesis and cell growth. 

mTOR is a protein kinase regulating cell growth, survival, metabolism, and immunity.

metformin can activate p53 by activating AMPK and thereby ultimately stop the cell cycle.

Metformin in nondiabetic, unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiation: survival exceeded expectations in both groups, those who received chemoradiation alone vs chemoradiation and metformin: however, the addition of metformin to chemoradiation did not improve overall or progression-free survival.

Addition of metformin to chemoradiotherapy, as a concurrent treatment as well as consolidation therapy, in patients without diabetes who have locally advanced non-small cell lung cancer 

addition of metformin to chemoradiotherapy was associated with worse treatment efficacy and increased toxic effects compared with chemoradiotherapy alone. 

The proportion of patients who experienced a failure event within 1 year with locoregional disease progression, distant metastases, death, or withdrawal was 69.2% in the metformin arm vs 42.9% in the control arm.

Metformin is not recommended as an adjunct to chemoradiotherapy for the treatment of unresected locally advanced non-small cell lung cancer in patients who do not have diabetes.

Addition of metformin to standard breast cancer treatment 

a randomized controlled trial (RCT) found addition of metformin to standard breast cancer treatment did not improve invasive disease free survival vs placebo among patients with high-risk operable disease who did not have diabetes.

Strong evidence for a lack of benefit from metformin treatment in metabolically healthy individuals.

A review found metformin use did not have a significant effect on cancer incidence in subjects with overweight/obesity and/or prediabetes/diabetes.

A clinical trial has demonstrated a beneficial effect in colon and breast cancers.

It possesses antioxidant activity.

Use associated with impaired cognitive performance.

Compared with Sulfonylureas, metformin is associated with reduced risk of major adverse cardiac events among patients with type two diabetes and reduced kidney function.

In non diabetics does not improve carotid intima-media thickness or carotid plaque scores.

May have a Preventative role In peripheral neuropathy induced by diabetes



Treatment with metformin prevents axonal atrophy and fiber degeneration.



Metformin stimulates  the expression of neurotrophic and angiogenic factors in the peripheral nerve.



Metformin attenuates inflammation of nerve tissue exposed to chronic hyperglycemia.



Metformin increases the expression of anti-inflammatory markers.

Studies have shown in patients with prostate cancer, colorectal cancer, pancreatic cancer, triple negative breast cancer,, HER2 positive breast cancer, multiple myeloma the median overall survival durations are increased in patients taking metformin than in patients who are not.

Among patients with high-risk operable breast cancer without diabetes, the addition of Met Forman versus placebo to standard breast cancer treatment did not significantly improve invasive disease free survival (Goodwin PJ).

Long-term metformin use is associated with a significantly lower risk of new onset prostate cancer and all cause mortality in patients with type two diabetes than sulfonylureas and more protective against prostate cancer but less protective against all cause mortality in those less than 65 years of age.

Metformin affects multiple key processes related to cell growth, proliferation, and survival.

Epidemiological studies suggest a decreased risk of lung cancer in diabetic patients treated with antidiabetic drugs, including metformin-39-45% decreased risk.

Lung cancer patients treated with first-line chemotherapy and metformin have superior outcomes to those treated with chemotherapy and other diabetic medications.

A study suggests patients using metformin before a diagnosis of COVID-19 only had a third of the mortality risk of their counterparts with no reported use of the drug.


In a study, which included more than 300,000 participants aged 55 or older, the use of low dose metformin was associated with a lower incidence of age-related macular degeneration (AMD).


The use of metformin was associated with a reduction in odds of developing AMD.


The  association is dose-dependent, with low to moderate doses of metformin being associated with the greatest benefit.


When assessing doses greater than 1080 g, there was no association with reduced odds of developing AMD at 2 years.


Among patients with diabetes, metformin use was associated with a decreased risk of AMD in patients without existing diabetic retinopathy, but was considered a risk factor for patients with existing diabetic retinopathy.



Metformin use over 2 years in adults aged 55 years and older is associated with 5% to 10% reduced odds ratio of developing AMD. 


A dose-dependent association of this potential protective effect is present, with low to moderate doses of metformin being associated with the lowest odds ratio for the development of AMD.

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