Metformin and Glyburide

What does Metformin do in the body?

Absorption: Metformin is absorbed over 6 hours, and its bioavailability is about 50 to 60% under fasting conditions.

When it taken together with food absorption is decreased and delayed. Some findings indicates that absorption level is not dose-dependent, suggesting that absorption occurs through a saturable process.

Some animal and in-vitro studies sugest that absorption occurs through a non-saturable, passive process, possibly involving a paracellular route. Maximum concentration in blood occurs 3 hours after oral administration.

Distribution: Maximum plasma concentrations are reached within 1-3 hours after taking immediate-release metformin tablet and 4-8 hours with extended-release formulations.

Metformin’s plasma protein binding is negligible, as reflected by its very high apparent volume of distribution. Steady state after metformin administration is usually reached in one or two days.

Metabolism: Metformin does not get trough the metabolism. It is eliminated from the body via tubular secretion and excreted unchanged in the urine. It can’t be detected  in plasma within 24 hours after oral administration.

Elimination: Metformin’s average elimination half-life in plasma is 6.2 hours. Metformin is distributed to and also appears to be accumulated in red blood cells, with a much longer elimination half-life of17.6 hours.


Glucophage (metformin) tablets
Glucophage (metformin) tablets

What is Glyburide?

Glyburide is a Generic name for an oral fast and short acting anti-diabetic drug that belong to the second generation sulfonylurea class.

The second generation means that this drug undergoes enterohepatic circulation, this generation drugs are more potent and have shorter half-lives than the sulfonylureas first-generation drugs such as: acetohexamide, carbutamide, tolbutamide and chlorpropamide.

Glyburide helps control blood sugar levels in blood by helping pancreas to produce insulin and helping the body use insulin efficiently.

Glyburide is used together with exercise and diet and sometimes in combination with other drugs to treat type 2 diabetes (non-insulin-dependent diabetes mellitus).

This drug will lower blood sugar levels in blood only in patients whose bodies produce insulin naturally, that’s why Glyburide is not used for the treatment of diabetes type 1or diabetic ketoacidosis. It is available in following doses: 1.25, 2.5, and 5 mg.

Popular Brand names on the market for products containing Glyburide as an active ingredient are:

  • Glynase,
  • Diabeta,
  • Micronase,
  • Semi-Daonil,
  • Daonil,
  • Delmide,
  • Euglucon, Glybovin.

It is also available in combination with metformin in one dosage form under the following Brand names: Benimet, Glucovance, Glibomet, Glucored and Glucored Forte.


How does Metformin and Glyburide work in the body?

Metformin reduces glucose levels in blood by decreasing the hepatic glucose production and intestinal glucose absorption, and by improving cell sensitivity to insulin by increasing peripheral uptake of glucose and utilization.

These effects are mediated by the initial activation of AMP-activated protein kinase which is a liver enzyme that plays a significant role in insulin signalization, energy balance, and the metabolism of glucose and lipids.

Activation of AMP- protein kinase is needed for inhibitory effect of metformin on liver cell production. Increased peripheral utilization of glucose is caused by improved insulin binding to its receptors.

Metformin administration also increases AMP- protein kinase in skeletal muscle cells. AMP- protein kinase is known to cause deployment of GLUT-4 to the cell plasma membrane, which results in insulin-independent glucose uptake.

The rare side effect called lactic acidosis can be caused by decreased liver uptake of lactate, which is one of the substrates of gluconeogenesis. Patients who have healthy renal function, the slight excess are simply cleared.

However, patients who have severe renal impairment the accumulation of lactic acid can be clinically significant. Conditions such as severe hepatic disease and acute/decompensated heart failure may precipitate lactic acidosis.

Glyburide’s primary mode of action, in which this drug lower sugar levels in blood, is stimulation of insulin secretion from the beta cells of pancreas, an effect which is dependent upon beta cells function in the pancreatic islets.

Glyburide binds to ATP-sensitive potassium-channel receptors located on the pancreatic cells membrane, reducing conductance of potassium and causing membrane depolarization.

Depolarization then stimulates influx of calcium ions through voltage-sensitive calcium channels, raising concentrations of calcium ions in cells, which then prompts the secretion of insulin.

Stimulation of insulin secretion in response to a meal is major importance for our body. Fasting insulin levels are not raised even on long-term use of Glyburide but the postprandial insulin response remains to be enhanced after at least 6 months of Glyburide therapy.

However, some patients fail to initially response, or during time gradually lose their responsiveness to sulfonylurea drugs and Glyburide generally. It has been shown that glyburide can decrease postprandial blood glucose, fasting plasma glucose and glycosolated hemoglobin (HbA1c) levels.

It is completely metabolized, likely in the liver. Glyburide metabolites may have a small hypoglycemic effect, however those effects is thought to be clinically unimportant. Glyburide metabolites are excreted in urine and feces in approximately equal proportions.

Can patients take Metformin and Glyburide together?

Glyburide and Metformin combination is indicated for the treatment of high blood sugar levels that are caused by diabetes mellitus type 2. Combination of these two drugs can help body to regulate high blood sugar levels on efficient way.

Glyburide stimulates insulin release from the pancreas, directing the body to store blood sugar and thus reducing the sugar levels in blood.

Metformin has three different modes of actions: it lowers intestines absorption of sugar, stops liver from converting stored sugar (glycogen) into blood sugar; and it helps body to use insulin more efficiently.

There are also products on the market containing the combination of metformin and Glyburide in one tablet, such as Benimet, Glucovance, Glibomet, Glucored and Glucored Forte.

However, under certain conditions and in some predisposed patients, too much metformin and Glyburide can cause lactic acidosis a serious condition.

Lactic acidosis symptoms are usually quick and severe to appear and usually occur when other health problems not related to the medicine are present and are very severe, such as a heart attack or kidney failure.

So, doctor should follow the beginning of therapy especially during the first few weeks that you take this medicine.

The table below shows the incidence of side effects after Metformin and Glyburide administration in recommendable doses. The incidence can be increased if these drugs are taken together or overdosed.

Frequency not defined Hypoglicemia, Asthenia, Diarrhea, Flatulence, Weakness, Myalgia, Upper respiratory tract infection, Hypoglycemia, GI complaints, Lactic acidosis (rare), Low serum vitamin B-12, Nausea/vomiting, Chest discomfort, Chills, Dizziness, Abdominal distention, Constipation, Dermatologic reactions, Diarrhea, Abdominal pain, Nervousness, Headache, Dizziness, Syncope, Anxiety, Erythema, Maculopapular eruptions, Morbilliform eruptions, Urticaria, Drowsiness, Cholestatic jaundice and hepatitis occur rarely but may progress to liver failure, Weight gain

Special precautions and warnings Metformin and Glyburide administration:

  • Before taking Metformin, patients should tell their doctor or pharmacist if they are allergic to metformin; or if they have any other allergies. Products with metformin may contain inactive ingredients that can cause allergic reactions or other problems.
  • Before using Metformin, patients should tell their doctor or pharmacist their medical history, especially if they ever had or have: breathing problems such as obstructive lung disease and asthma, blood problems such as anemia or vitamin B12 deficiency, kidney or liver disease.
  • Patients using Metformin should tell their doctors that they are using metformin before having surgery or any X-ray scanning procedure that use injectable iodinated contrast material.
  • Patients on a Metformin therapy may experience blurred vision, drowsiness or dizziness, or due to extremely low or high blood sugar levels. They should not drive, use machinery, or do any activity that requires alertness or clear vision until they are sure that they can perform such activities safely.
  • Patients using Metformin should limit the usage of alcohol while using this medication because alcohol can increase the risk of lactic acidosis and low blood sugar can be developed.
  • High fever, diuretic such as hydrochlorothiazide, too much sweating, prolonged diarrhea, and vomiting may cause dehydration and increase the risk of lactic acidosis. Patients should stop taking metformin and tell their doctor if they have prolonged diarrhea or vomiting.
  • It may be harder to control your blood sugar when your body is stressed (such as due to fever, infection, injury, or surgery). Consult your doctor because increased stress may require a change in your treatment plan, medications, or blood sugar testing.
  • Geriatric patients on Metformin therapy may be at higher risk for side effects such as low blood sugar or lactic acidosis.
  • Pregnant patients should use Metformin only when it is clearly needed. Patients should discuss the risks and benefits with their doctor. Doctor may direct to use insulin instead of metformin during pregnancy.
  • Metformin can make changes in the menstrual cycle, such as promote ovulation and this drug may also increase the risk of becoming pregnant.
  • Metformin can pass into breast milk, but only in small amounts. Patients should consult their doctor before breast-feeding.
  • Patients should not use Glyburide if they are in a state of diabetic ketoacidosis
  • Before taking Glyburide, patients should tell their doctor if they have liver or kidney disease, blockage of intestine chronic, diarrhea, deficiency of glucose-6-phosphate dehydrogenase (G6PD), a disorder of adrenal or pituitary glands, or a history of heart disease, or if they are malnourished.
  • Patients should now, that Glyburide therapy is only part of a complete antidiabetic program that may also include diet, weight control, exercise, and testing blood sugar. Patients should follow their therapy, diet, and exercise routines carefully. Changing any of these factors can affect your blood sugar levels.
  • Alcohol may make the side effects of Glyburide Consuming alcohol together with Glyburide may rarely cause symptoms such as: flushing (reddening of the face), vomiting, chest pain, weakness, headache, nausea, blurred vision, sweating, choking, mental confusion, breathing difficulty, and anxiety.
  • Glyburide may make skin sensitive to sunlight.
  • Glyburide and all sulfonylureas drugs are associated with weight gain, but less so than insulin. Sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals.

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