A new class of diabetes medications including Kombiglyze XR shows promising results, but the side effects may be more severe than patients are led to expect.

What’s in Kombiglyze XR?

Kombiglyze XR
consists of saxagliptin and metformin, two diabetes medications that use different mechanisms of action. This particular combination was first approved by the FDA in November 2010.

Metformin is an older diabetes medication that lowers blood sugar by decreasing glucose absorption from food within the intestines and by reducing the production of glucose by the liver.

Saxagliptin is one of a newer class of diabetes medications known as dipeptidyl peptidase-4 inhibitors, or DPP-4 inhibitors. These drugs work by reducing the ability of an enzyme, DPP-4, to break down incretin hormones.

Incretins direct the pancreas to produce more insulin, and they also make the liver produce less glucose. Drugs like saxagliptin get DPP-4 out of the way so that incretins can do their jobs, resulting in lower blood sugar.

Saxagliptin has an advantage over other diabetes medications in that it can lower blood sugar without encouraging weight gain. That characteristic has helped driven annual sales of saxagliptin-based medications into the hundreds of millions of dollars.

Kombiglyze XR Side Effects

In April 2016, the FDA issued a new Drug Safety Communication announcing that it would require saxagliptin-based drugs like Kombiglyze XR to carry a warning about a possibly increased risk of heart disease.

In patients with heart failure, the heart cannot move as much blood as the body needs to function properly. The risk is apparently higher in patients with diabetes who also suffer from heart disease or kidney disease.

The agency rationalized the warning based on the results of two large clinical trials conducted in patients with existing heart disease. Those trials showed that patients taking saxagliptin were hospitalized for heart failure at a higher rate than those who took a placebo.

These findings were consistent with those in a study published in September 2013. Researchers there did not find any evidence that a saxagliptin-based medication could protect the heart. They did find evidence suggesting an increased likelihood of heart failure, however.

Other studies have found a possible link between saxagliptin medications and pancreatic complications, including pancreatitis and pancreatic cancer.

A study published in 2013 found pre-cancerous changes in the pancreatic tissue of people who had taken incretin-based medication for type 2 diabetes. They also found early-stage tumors known as adenomas, which have the potential to grow and become malignant.

The current warning label for Kombiglyze XR also notes that there have been some reports of acute pancreatitis in patients taking saxagliptin. That warning has been in place since the FDA added it in November 2011. Pancreatitis itself can be a precursor to pancreatic cancer.

Still other studies have suggested a possible link to thyroid cancer. Review of reports submitted to the FDA’s adverse event reporting system revealed an increased instance of thyroid cancer in patients taking other types of incretin-based therapies for diabetes.

Due to the relatively new nature of these medications, researchers expressed concern that they are being over-promoted without adequate knowledge of their long-term beneficial outcomes.