Exenatide is taken by injection twice daily and is approved for use alone or in combination with a variety of oral diabetes drugs. Liraglutide is also taken by injection, but only once daily. Both products are sold in prefilled pens (similar to insulin pens). These drugs can lower HbA1c by about 1%.
Another big advantage of these drugs is that their use often leads to weight loss. This occurs because they slow the rate at which food is moved from the stomach to the intestines, thus prolonging the feeling of fullness after a meal. They may also signal the brain to directly reduce feelings of hunger. Common side effects of these drugs include nausea and vomiting, particularly when just starting therapy. It is important with either drug to increase the dose slowly from a low level to avoid these side effects as much as possible. Exenatide is removed from the body by the kidneys and is therefore not recommended for people with impaired kidney function. This is not the case for liraglutide, however, so people with kidney problems can usually take liraglutide if they are unable to take exenatide for this reason.
Dipeptidyl-peptidase-4 (DPP-4) inhibitors are not included in the ADA/EASD algorithm as a recommended treatment for Type 2 diabetes — in fact, none of the remaining treatments discussed in this article are. But like other classes of drugs that will follow, DPP-4 inhibitors are approved to treat Type 2 diabetes and may be helpful to some individuals. DPP-4 inhibitors work in a way similar to that of GLP-1 receptor agonists. But while those drugs mimic the naturally occurring hormone GLP-1, DPP-4 inhibitors block the action of an enzyme (known as DPP-4) that breaks down GLP-1 throughout the body. By slowing the effects of this enzyme, DPP-4 inhibitors allow GLP-1 to stay in the body longer (where the hormone increases insulin production and reduces the release of glucose from the liver).
There are currently three DPP-4 inhibitors approved for use in the United States: sitagliptin (Januvia), saxagliptin (Onglyza), and linagliptin (Tradjenta). Advantages of DPP-4 inhibitors include once-daily oral dosing and a low risk of hypoglycemia. Common side effects of DPP-4 inhibitors include headache, upper respiratory tract infection, and sinus infection.
Nateglinide (Starlix) and repaglinide (Prandin) are the two currently available drugs that belong to the meglitinide family. This class of drugs works in a way very similar to that of sulfonylureas, leading to increased insulin production in the pancreas. However, meglitinides are short-acting, taking effect within 15–30 minutes of being ingested and lasting for only 4–6 hours. They should be taken within 30 minutes of beginning a meal and are usually taken three times per day — but should be skipped if a meal is skipped.
Because meglitinides work by increasing the amount of insulin in the body, common side effects include hypoglycemia and weight gain. Taking them as directed with meals, however, lowers the risk of hypoglycemia. Although nateglinide is available as a generic, meglitinides tend to be more expensive than sulfonylureas.
Pramlintide (Symlin) is an injectable drug that is sometimes taken alongside mealtime insulin. It is a synthetic version of amylin, a hormone that is normally released from the pancreas along with insulin and may be lacking in people with Type 2 diabetes. Pramlintide works with insulin to regulate blood glucose levels after meals, effectively increasing the potency of insulin. It is taken by injection immediately before a meal and should never be mixed with insulin or any other drug in the same syringe. Potential benefits of pramlintide include allowing users to take less insulin with each meal, which may in turn lead to some weight loss. A major concern with the drug, however, is the risk of severe hypoglycemia it carries — particularly for people just starting to take it. People who begin to take pramlintide must reduce their mealtime insulin dose by about half, or as instructed by their doctor, to avoid a potentially dangerous drop in blood glucose. While weight loss and improved blood glucose control are not benefits to scoff at, the risk of hypoglycemia and the need for three or more additional injections per day are drawbacks of pramlintide. It is also only available as a brand-name medicine and can therefore be expensive under many insurance plans.