The more you know about your diabetes medications, the more likely you are to stick with the regimen and know the right questions to ask your prescriber. Let’s take a deeper look at one of the drug classes becoming more commonly used to treat type 2 diabetes, the dipeptidyl-peptidase-4 enzyme inhibitors, also known as DDP-4 inhibitors or gliptins. (Each of the drugs in this class has a generic name ending with “gliptin.”)
Which drugs are we talking about?
Sitagliptin (Januvia) was approved in 2006, and is probably the best known in the class. Others are alogliptin (Nesina), linagliptin (Tradjenta) and saxagliptin (Onglyza). They are also packaged in a combination pill with metfomin under various brand names. Alogliptin (Nesina) is the only one available as a generic medication. The cash price for a month’s supply of any of the brand name gliptins is around $300, with the generic alogliptin being about half of that.
How do these drugs work?
The action of DPP4 inhibitors is a little bit complicated. When we eat, two main hormones are released by the gut, GIP and GLP-1. The role of GIP and GLP-1 is to stimulate the pancreas to produce insulin in response to food, mostly sugars and fat.
In addition to insulin secretion, GLP-1 can also reduce glucagon concentrations, the hormone that opposes the action of insulin. The enzyme called DPP-4 is responsible for breaking down GLP-1. The DPP-4 inhibitor drugs work by blocking this enzyme, which then lets GLP-1 stay around and do its job of lowering post-meal glucose.
Impact on A1C
Because of the actions of DDP-4 inhibitors, these drugs are better at reducing blood glucose after a meal than lowering fasting glucose levels. Their ability to drive down the A1C isn’t breaking any records. Most people who take a drug from this class see an improvement in A1C of 0.5% to 0.8%, compared to up to 2% with metformin. There have not been any trials directly comparing the four drugs in the class, but from a clinical perspective, there does not seem to be any difference between them with regard to efficacy or side effects.
The gliptins have many favorable attributes and minimal side effects. They are dosed once a day and do not cause hypoglycemia or weight gain, which are significant issues in diabetes. They can be used at reduced doses when kidney function is declining. One drug in the class, linagliptin (Tradjenta) does not require any dose adjustment for poor kidney function.
There aren’t any significant disadvantages, but the high cost and smaller impact on A1C may prevent them from being prescribed more often.
Clearing Up Concerns
One of the main long-term concerns of having diabetes is the relationship between diabetes and cardiovascular disease. The FDA now requires that all new diabetes drugs prove that they are heart safe before being given full approval. Knowing that there are no drug-related heart risks is kind of a big deal. Earlier studies with gliptins showed mixed results regarding a possible link to heart failure. Although a warning was added to the FDA labeling of every drug in the class in April 2016, a more recently published study found no higher risk of heart failure in diabetes patients taking gliptins versus other diabetes medications.(1) It appears that all of the gliptin drugs have been cleared of this potential issue, but some prescribers may still choose to avoid them when heart failure is present.
The possibility of an association with pancreatitis has also been investigated.(2) Any risk of pancreatitis with gliptins is very low and is more likely due to diabetes itself. Factors that contribute to pancreatitis are alcohol or tobacco use, gallstones, high triglycerides or obesity. If you are taking one of the gliptins and experience symptoms of pancreatitis, report to your doctor immediately. These symptoms include significant abdominal pain (especially after eating), swollen and tender abdomen, fever, rapid pulse, nausea and vomiting.
Place in Therapy
The gliptins will most likely continue to be prescribed after metformin, or after a metformin-sulfonylurea combination. Their use has increased quite a bit in recent years because of a low risk of hypoglycemia, neutral effects on body weight, and relatively rare adverse effects. Nevertheless, their high cost and modest efficacy may be limiting factors for some people.
Overall, this class of drugs is well-tolerated and is considered an effective part of an oral drug regimen in type 2 diabetes.
What benefits or problems have you experienced with any of the gliptin medications?
Yang T, Shen M, Huang Yet al. Acute pancreatitis in patients with type 2 diabetes mellitus treated with dipeptidyl peptidase-4 inhibitors. Journal of food and drug analysis 2016;24:450-454.
Toh S, Hampp C, Reichman ME et al. Risk for Hospitalized Heart Failure Among New Users of Saxagliptin, Sitagliptin, and Other Antihyperglycemic Drugs. Annals of Internal Medicine 2016.
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