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Drugs and Treatment for Type 2 Diabetes

By Laurie Marbas, M.D. ; Updated August 14, 2017

Type 2 diabetes can be treated with oral prescription medications and/or insulin that is injected subcutaneously (as a shot).

Oral Agents

1) Biguanides: The first medication prescribed to a newly diagnosed Type 2 diabetic is often metformin because it does not cause weight gain or hypoglycemia, and it is inexpensive. It decreases liver glucose production and increases insulin sensitivity. Since it improves the body’s use of insulin, overall insulin levels decrease. It is the only oral medication approved for use in children and adolescents. Kidney function should be evaluated prior to starting metformin. It should not be prescribed for those who have heart failure, kidney disease, liver disease, excessive alcohol intake or serious infection. Side effects include gastrointestinal disturbances like diarrhea, but they usually improve over time and can be reduced by taking with food. Metformin decreases the absorption of B-12, so levels should be monitored. Metformin should be stopped prior to any imaging that uses intravenous contrast and for 48 hours afterward.

2) Sulfonylureas: Glipizide, glyburide and glimeperide are the most common prescribed oral diabetic medications. Glipizide is shorter-acting and is preferred for elderly patients or those with renal disease. Glyburide should not be used in individuals with renal disease because it has an active metabolite eliminated by the kidneys. Sulfonylureas stimulate the pancreatic beta cells to release insulin and may cause hypoglycemia and weight gain. These drugs may be used in individuals with sleep apnea or congestive heart failure.

3) Thiazolidinediones: Pioglitazone and rosiglitazone increase insulin sensitivity and decrease the liver’s glucose production. They should be avoided in individuals with heart failure and nonalcoholic liver disease. Weight gain and fluid retention are common side effects, but also seen are increased risks for distal limb fractures in women, heart failure and bladder cancer. There is a black box warning on this medication for class III or IV heart failure.

4) Meglitinides: Nateglinide and repaglinide stimulate insulin secretion. They are short-acting and therefore must be taken with meals, which is helpful for irregular eating schedules. They can also be used for elderly patients as well as those with renal failure and heart failure.

5) Alpha-glucosidase inhibitors: Acarbose and miglitol delay carbohydrate absorption in the gut, decrease postprandial, or after-meal, glucose levels and do not cause hypoglycemia when used as an individual therapy. Flatulence is a common side effect, but it generally improves over time. Individuals should have liver function tests monitored, and these medications should be avoided in individuals with cirrhosis, kidney disease or gastrointestinal disease.

6) Dipeptidyl peptidase-4 or DPP-IV inhibitors: Sitagliptin, saxagliptin, linagliptin and vildagliptin inhibit the enzyme that degrades the body’s incretin hormones. Incretin is a hormone that stimulates insulin secretion in response to the ingestion of food. If the enzyme that breaks down incretins is blocked, then the incretins will hang around longer, causing an increase in insulin secretion, a decrease in glucagon (a hormone that causes the liver to release more glucose) and a delay in stomach emptying (which slows the absorption of carbohydrate and therefore decreases the blood glucose level after meals). Sitagliptin must be given at a lower dose for those with kidney disease, but linagliptin is not excreted from the kidneys, therefore it is a good choice for the elderly. Side effects include an increase in upper respiratory infections, sore throats, diarrhea and pancreatitis.

7) SGLT2 inhibitors: canagliflozin and dapagliflozin block reabsorption of glucose in the kidney and therefore increase urinary excretion of glucose. This causes a decrease in weight and blood pressure, however, it increases risk of urinary tract infections and vaginal yeast infections.

8) Bile acid sequestrant (colesevelam): Cholesterol is the major precursor of bile acid. Colesevelam binds with bile acids in the intestine and eliminates it in the feces, leading to lower serum cholesterol. It causes a reduction in A1c and may increase incretins.

Noninsulin Injectables

1) Incretin mimetic, or GLP-1 receptor agonists (liraglutide and exenatide): Exenatide is injected and used to increase mealtime insulin secretion in Type 2 diabetics. It mimics incretin, which is a hormone that stimulates insulin secretion in response to the ingestion of food. It is less likely to cause low blood sugar or weight gain and promotes feelings of fullness, thus leading to decreased appetite and weight loss. There is a black box warning regarding increased risk for thyroid C-cell tumors, and it is contraindicated in patients with a personal or family history of multiple endocrine neoplasia syndrome type 2.

2) Amylin is made by the pancreatic beta cells, which is secreted with insulin. Pramlintide, a synthetic amylin, is injected at mealtimes along with fast-acting insulin. It reduces post-meal blood glucose levels and decreases appetite, which aids in weight loss. It is contraindicated in individuals with gastroparesis. There’s a black box warning regarding an increased risk of severe hypoglycemia.


Insulin comes in a variety of forms with different durations of action:

  • Long-acting insulins give baseline (or basal) coverage. Glargine is typically given daily, and detemir is given once or twice a day. 
  • NPH (neutral protamine hagedorn, or insulin human isophane) is an intermediate-acting insulin and is administered twice a day. 
  • Rapid-acting insulins, or regular insulin (lispro, aspart, glulisine), are given in boluses prior to meals to lower the post-meal glucose levels and to treat elevated blood glucose levels related to other causes. 
  • Intermediate-acting insulin is also available in combination with short- or rapid-acting insulin.
  • Insulin causes weight gain, but the benefit of glucose control is more important.
  • The average insulin dose is 0.6 to 0.8 units/kg of body weight per day.
  • Injections in the abdomen are absorbed faster than when injected in the thigh, however, exercise accelerates absorption in the thigh.

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