A study of Merck’s Januvia (sitagliptin), a drug for patients with type 2 diabetes, has found that its use can lead in some patients to a low-grade form of pancreatitis and an increased risk of pancreatic cancer in the long term. However, the study, conducted at the Larry L. Hillblom Islet Research Center at UCLA, also found that the risks associated with Januvia as a monotherapy are removed when the drug is used in conjunction with metformin (trade name Glucophage). Metformin, a low-cost drug that controls glucose production by the liver, is one of the oldest and most benign standbys in the anti-diabetes arsenal.
The researchers found that Januvia caused pancreatic abnormalities that are established risk factors for pancreatitis and, in the long run, pancreatic cancer. The problem may derive from Januvia’s ability to spur the production-sometimes to exceptionally high levels-of cells that line the pancreatic ducts, which can lead to abnormalities.
Januvia increases the effectiveness of a digestive hormone called glucagon-like peptide (GLP-1), which lowers blood sugar levels in type 2s. Concerns that it may induce problems with the pancreas call to mind recent suspicions by the FDA that Byetta, a similar drug, may have been a causative factor in several cases of severe pancreatitis that later led to death.
In Byetta’s case, manufacturers Amylin and Eli Lilly have asserted that the FDA has not been able to show a direct connection between taking Byetta-which has over 600,000 users-and severe or fatal pancreatitis among a small group (30) of those users.
The UCLA study’s determination that metformin mitigates Januvia’s ill effects is welcome news. The researchers found that the two drugs worked synergistically, preserving pancreatic beta cells and increasing insulin sensitivity in rats. There was no abnormal production of pancreatic duct cells when the drugs were used in combination, unlike when Januvia was used as a standalone.
The study’s authors cautioned that although the results seem to show a way that GLP-1 drugs can be used without worry about their effects on the pancreas, any final conclusions will have to await testing on human subjects. In the meantime, though, they advised doctors and healthcare providers to err on the side of caution and prescribe Januvia only in combination with metformin.
A Merck representative asked that we include the following:
It is important to note that this study was limited to a very small number of transgenic rats, which may not be relevant to patients with type 2 diabetes. As the author himself noted in the study, it is possible that the adverse effects observed in his rat study would not occur in humans.
Given how important it is for patients to manage their diabetes, we do not want patients to over-react to the animal findings in a small study. In fact, if a patient has questions, we would encourage them to speak with their physician.