November 30, 2015
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Diabetes Treatment (cont.)

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Historically, increasing insulin output by the pancreas has been the major area targeted by medications used to treat type 2 diabetes. Medications that increase insulin output belong to the class of drugs called sulfonylureas. Older generations of these drugs include chlorpropamide (Diabinese) and tolbutamide were abandoned due to association with higher risk of cardiovascular events.

Newer sulfonylurea drugs include:

  • glyburide (DiaBeta),
  • glipizide (Glucotrol), and
  • glimepiride (Amaryl).

These drugs rapidly lower blood sugar, but can cause abnormally low blood sugar (called hypoglycemia). In addition, sulfonylureas contain sulfa and should be avoided by patients who are allergic to sulfa.

Metformin (Glucophage)

Biguanides is a class of drugs that decrease the amount of glucose produced by the liver, and have been used for many years in Europe and Canada. In 1994, the FDA approved the use of the biguanide called metformin (Glucophage) for the treatment of type 2 diabetes.

  • Metformin is unique in its ability to decrease glucose production by the liver.
  • Because metformin does not increase insulin levels, metformin when used alone does not usually cause hypoglycemia. In addition, metformin tends to suppress appetite, which may benefit overweight patients.
  • Metformin may be used by itself or together with other oral drugs or insulin.
  • Metformin should not be used in patients with kidney impairment and should be used cautiously in those with liver impairment.

The older biguanides that preceded metformin were associated with a serious condition called lactic acidosis, a potentially dangerous acid build up in the blood resulting from accumulation of the drug and its breakdown products. While metformin is safer in this regard, it is recommended that metformin be discontinued for 24 hours before surgery or any procedure involving the intravenous injection of dyes (for example, some X-ray studies of the kidney). The dyes may impair kidney function and cause a buildup of the drug in the blood. Metformin can be restarted after these procedures once the patient is urinating normally.

Canagliflozin (Invokana) and dapagliflozin (Farxiga)

The FDA approved canagliflozin (Invokana) in March 2013 and dapagliflozin (Farxiga) in January 2014 to improve blood sugar control (glycemic control) in adults with type 2 diabetes. These oral medications belong to a class of drugs known as sodium-glucose co-transporter 2 (SGLT2) inhibitors. They work by blocking the kidneys' reabsorption of glucose, leading to increased glucose excretion and reduction of blood sugar levels.

Clinical trials with canagliflozin involving over 10,000 patients showed improvement in both fasting glucose and hemoglobin A1c (HbA1c) levels. Sixteen clinical trials with dapagliflozin involving over 9,400 participants showed improvement in HbA1c levels.

Side effects, warnings, and precautions

  • Side effects are similar for both canagliflozin and dapagliflozin and include vaginal yeast infection and urinary tract infection.
  • Each of these drugs has been used as a single therapy and in combination with other drugs such as metformin, sulfonylurea, pioglitazone, and insulin.
  • Dapagliflozin is contraindicated in patients with a history of bladder cancer.
  • Due to risk of dehydration, these drugs should be used cautiously in the elderly as well as those with impaired renal function or taking diuretics.
Medically Reviewed by a Doctor on 5/7/2015


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