What is Metformin? What is Insulin?

Metformin is an oral medication that lowers blood glucose (sugar) by influencing the body’s sensitivity to insulin and is used for treating type 2 diabetes. Metformin increases the sensitivity of liver, muscle, fat, and other tissues to the uptake and effects of insulin, which lowers the blood sugar levels. Metformin does not increase the concentration of insulin in the blood and does not cause low blood glucose levels (hypoglycemia) when used alone. Metformin can reduce complications of diabetes such as heart disease, blindness, and kidney disease. Metformin is also used to treat polycystic ovaries and weight gain due to medications used for treating psychoses.

Insulin is a naturally-occurring hormone secreted by the pancreas and used by the cells of the body to remove and use glucose from the blood. People with diabetes mellitus have a reduced ability to take up and use glucose from the blood and the glucose level in the blood rises. In type 1 diabetes, the pancreas cannot produce enough insulin. In type 2 diabetes, patients produce insulin, but cells throughout the body do not respond normally to the insulin. By increasing the uptake of glucose by cells and reducing the concentration of glucose in the blood, insulin prevents or reduces the long-term complications of diabetes, including damage to the blood vessels, eyes, kidneys, and nerves. Insulin is administered by injection under the skin (subcutaneously).

What are the side effects of metformin and insulin?

Metformin

The most common side effects with metformin are

These symptoms occur in one out of every three patients. These side effects may be severe enough to cause therapy to be discontinued in one out of every 20 patients. These side effects are related to the dose of the medication and may decrease if the dose is reduced.

Metformin may also cause:

A serious but rare side effect of metformin is lactic acidosis. Lactic acidosis occurs in one out of every 30,000 patients and is fatal in 50% of cases. The symptoms of lactic acidosis are

  • weakness,
  • trouble breathing,
  • abnormal heartbeats,
  • unusual muscle pain,
  • stomach discomfort,
  • light-headedness, and
  • feeling cold.

Patients at risk for lactic acidosis include those with reduced function of the

Insulin

Hypoglycemia is the most common side effect that may occur during insulin therapy. Symptoms of hypoglycemia include:

  • Confusion
  • Nausea
  • Hunger
  • Tiredness
  • Perspiration
  • Headache
  • Heart palpitations
  • Numbness around the mouth
  • Tingling in the fingers
  • Tremors
  • Muscle weakness
  • Blurred vision
  • Cold temperature
  • Excessive yawning
  • Irritability
  • Loss of consciousness

Patients may experience blurred vision if they have had elevated blood sugar levels for a prolonged period of time and then have the elevated levels rapidly brought to normal. This is due to a shift of fluid within the lens of the eye. Over time, vision returns to normal. Other side effects that may occur include headaches, skin reactions (redness, swelling, itching or rash at the site of injection), worsening of diabetic retinopathy, changes in the distribution of body fat (lipodystrophy), allergic reactions, sodium retention, and general body swelling. Insulin causes weight gain and may reduce potassium blood levels. In addition to these side effects, inhaled insulin

(Afrezza) may cause throat pain or irritation and cough and patients should inform their healthcare professional of any unresolved symptoms affecting the lungs for follow up.

Type 2 Diabetes Diagnosis, Treatment, Medication

What is the dosage of metformin vs. insulin?

Metformin

  • For treating type 2 diabetes in adults, metformin (immediate release) usually is begun at a dose of 500 mg twice a day or 850 mg once daily. The dose is gradually increased by 500 mg weekly or 850 mg every two weeks as tolerated and based on the response of the levels of glucose in the blood. The maximum daily dose is 2550 mg given in three divided doses.
  • If extended tablets are used, the starting dose is 500 mg or 1000 mg daily with the evening meal. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg except for Fortamet (2500 mg of Fortamet, once daily or in two divided doses). Glumetza tablets (500 -1000mg formulations are given once daily (either 1000 to 2000mg). Fortamet and Glumetza are modified release formulations of metformin. Metformin should be taken with meals.
  • For pediatric patients 10-16 years of age, the starting dose is 500 mg twice a day. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg in divided doses.
  • Children older than 17 years of age may receive 500 mg of extended release tablets daily up to a maximum dose of 2000 mg daily. Extended release tablets are not approved for children younger than 17 years of age.
  • Metformin-containing drugs may be safely used in patients with mild to moderate renal impairment. Renal function should be assessed before starting treatment and at least yearly.
  • Metformin should not be used by patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2 and starting metformin in patients with an eGFR between 30-45 mL/minute/1.73 m2 is not recommended.
  • Metformin should be stopped at the time of or before administering iodinated contrast in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Kidney function should be evaluated 48 hours after receiving contrast and metformin may be restarted if kidney function is stable.

Insulin

The abdomen is the preferred site for insulin injection, but the sites of injection must be rotated in order to prevent erosion of the fat beneath the skin, a condition called lipodystrophy. Dosing is adjusted for each patient. A combination of short acting/rapid acting and intermediate insulin or long acting insulin are typically used.

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What drugs interact with metformin and insulin?

Metformin

  • Cimetidine (Tagamet), by decreasing the elimination of metformin from the body, can increase the amount of metformin in the blood by 40%. This may increase the frequency of side effects from metformin.
  • Ioversol (Optiray) and other iodinated contrast media may reduce kidney function, which reduces elimination of metformin, leading to increased concentrations of metformin in the blood. Metformin should be stopped 48 hours before and after use of contrast media.
  • Thiazide diuretics, steroids, estrogens, and oral contraceptives may increase blood glucose and reduce the effect of metformin. When these drugs are stopped, patients should be closely observed for signs of low blood glucose.
  • Alcohol consumption increases the effect of metformin on lactate production, increasing the risk of lactic acidosis.

Insulin

A number of substances affect glucose metabolism and may require insulin dose adjustment and particularly close monitoring.

The following are examples of substances that may reduce the blood glucose-lowering effect of insulin that may result in hyperglycemia:

The following are examples of substances that may increase the blood glucose-lowering effect of insulin and susceptibility to hypoglycemia: oral antidiabetic products, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, pentoxifylline, propoxyphene, salicylates, and sulfonamide antibiotics.

Beta-blockers, clonidine, lithium salts, and alcohol may either increase or reduce the blood glucose-lowering effect of insulin. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.

In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine, and reserpine, the signs and symptoms of hypoglycemia may be reduced or absent.

Bronchodilators and other inhaled products may alter the absorption of inhaled human insulin.

(The above insulin drug interaction section is from FDA prescribing information)

Are metformin and insulin safe to use while pregnant or breastfeeding?

Metformin

  • There are no adequate studies in pregnant women. Most experts agree that insulin is the best treatment for pregnant women with diabetes.
  • Metformin is excreted into breast milk and can therefore be transferred to the nursing infant. Nursing mothers should not use metformin.

Insulin

  • Insulin is the drug of choice for controlling diabetes during pregnancy, that is, it is preferred over oral drugs to reduce blood sugar. NPH, insulin aspart, insulin detemir, and insulin lispro also are used during pregnancy.
  • Insulins are considered safe to use by nursing mothers.

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Medically Reviewed on 1/18/2019

References

REFERENCE:

FDA Prescribing Information