Last Monday, May 2, the FDA approved a new medication for type 2 diabetes. It’s pretty safe to argue that this is a common co-morbidity among patients in rehabilitation. And as far as medications that are important in physical therapy go, those that can change blood glucose (either raising or lowering it) are probably medications that physical therapists and other rehabilitation professionals should understand. The new drug, an inhibitor of dipeptidyl peptidase-4 (DPP-4), is linagliptin (Tradjenta™). It joins 2 other DPP-4 inhibitors available in the US, sitagliptin (Januvia™) and saxagliptin (Onglyza™) among a large number of treatment options for people with type 2 diabetes.

What is DPP-4 and why inhibit it, you might ask? This is an enzyme that breaks down incretin hormones, chemicals produced within the gastrointestinal tract in response to an ingested, carbohydrate-containing meal. There are several hormones that belong to this group, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). The most important action of these hormones, especially GLP-1, is to stimulate insulin release by the pancreas. The drug does this in a glucose-dependent manner, meaning that hypoglycemia is relatively uncommon. GLP-1 only stimulates the pancreas to produce insulin to the degree that glucose levels increase – more glucose, more stimulation of insulin secretion and vice versa. Other effects of the incretins include the suppression of glucagon secretion, gastric emptying, and appetite, and maybe even the stimulation of beta cell proliferation in the pancreas.¹ The beta cells, remember, are responsible for producing insulin, so this is a good thing if it is happening. By inhibiting the action of the enzyme that breaks these incretin hormones down, there are more molecules of the hormones available for a longer period of time, increasing their effects. The bottom line is that these drugs lower blood glucose, whether you are looking at finger sticks or A1C. Linagliptin, like the other DPP-4 inhibitors, can be taken alone or in combination with other oral diabetes medications. It has not been studied in combination with insulin.²

In rehabilitation, the DPP-4 inhibitors do not create any major issues, and linagliptin seems to fall in line with the other members of the drug class. The most common adverse effects might be important to the patient, but don’t really factor into rehabilitation management – these include a stuffy or runny nose, or a sore throat. In rehabilitation, the major concern with drugs that are capable of lowering blood glucose is hypoglycemia. Because of the way these drugs work, there is not a significant risk of hypoglycemia associated  with linagliptin or any of the other DPP-4 inhibitors. The risk increases when a patient is also taking a sulfonylurea, but therapists should already be wary of hypoglycemia in individuals taking sulfonylureas. Pancreatitis has been noted to occur more often in patients being treated with linagliptin (as well as sitagliptin) than in those taking a placebo, but the absolute risk is very small. Any patient with signs or symptoms of acute pancreatitis – new onset of abdominal discomfort and tenderness, nausea and vomiting – should warrant the concern of the treating therapist, whether or not a medication is implicated in producing the problem.

These drugs have only been “in the wild” since October of 2006, when sitagliptin was approved by the FDA, so it remains to be seen what other concerns might arise with long-term use of these agents. DPP-4 is expressed in many other tissues in the body, and the long-term effects of inhibiting its action are unknown.³

Now you have one less question to ask when you see patients coming in to your clinics taking yet another drug you’ve never heard of. And remember, just because it’s new doesn’t mean it’s better than drugs that are already out there.

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1. Langley AK, Suffoletta TJ, Jennings HR. Dipeptidyl peptidase IV inhibitors and the incretin system in type 2 diabetes mellitus. Pharmacotherapy. 2007;27:1163-1180.
2. Boehringer Ingelheim Pharmaceuticals. Tradjenta™ prescribing information. Available at http://www.tradjenta.com. Accessed May 12, 2011.
3. Sitagliptin/metformin (Janumet) for type 2 diabetes. Med Lett Drugs Ther. 2007;49:45-47.