Januvia^TM (sitagliptin) is a DPP-4 (dipeptidyl peptidase) inhibitor that works to increase the production of insulin from the pancreas and decrease the production of glucose from the liver. It may be used alone as an addition to lifestyle modifications (including diet and exercise) or it can be used in combination with metformin, glimepiride, metformin plus glimepiride, Avandia®, or Actos®. Januvia^TM is taken only once daily and may be taken with or without food. Januvia^TM lowers A1C by approximately 0.7 percent.

Adverse effects of Januvia^TM are rare but include a mild headache, upper respiratory infection, stuffy or runny nose, sore throat, or diarrhea. Januvia^TM has also been linked to a serious allergic reaction. This may be indicated by difficulty breathing, swelling of the tongue or mouth, or rash. Individuals experiencing any of these symptoms while taking Januvia^TM should stop taking it and contact a physician or an emergency department immediately.

Byetta^TM (exenatide) is an analog of GLP-1 (glucagon-like peptide), a hormone that is necessary for the body’s use of food. Like Januvia^TM, Byetta^TM also increases insulin production from the pancreas. Additionally, it slows gastric emptying and increases a person’s feeling of fullness. Byetta^TM is used in combination with other medications, including metformin, Avandia®, Actos®, glipizide, glimepiride, and glyburide. Byetta^TM can lower A1C by approximately 0.5 to 1 percent.

Due to its effect on a patient’s feeling of fullness, Byetta^TM has been associated with weight loss. However, because Byetta^TM is a relatively new product, long term data concerning maintenance of this weight loss is lacking. The longest period of time the effect has been studied is two years, and at that point, the average reduction from initial weight was 10 pounds. This was a progressive weight loss, as the average weight loss at week 30 was five pounds. Initial reductions in A1C were maintained at two years, with 50 percent of those studied achieving an A1C of less than or equal to 7 percent.

Unlike Januvia^TM, which is an oral tablet, Byetta^TM is an injection that can be administered into the fatty tissue of the abdomen, thigh, or upper arm. It is injected twice daily within 60 minutes prior to breakfast and dinner, or the two main meals of the day as long as they are separated by at least six hours. Byetta^TM is available in a pre-filled pen. Although they are initially refrigerated, Byetta^TM pens may be stored at room temperature after first use. Pens should be discarded 30 days after initial use, even if some drug remains in the pen.

Adverse effects of Byetta^TM are more significant than those associated with Januvia^TM and include nausea, vomiting, diarrhea, dizziness, headache and jitteriness. The gastrointestinal adverse effects (nausea, vomiting, and diarrhea) are most common and appear to be dose-related. They can be lessened by a gradual dose increase and with continued use. Low blood sugar reactions have been observed when Byetta^TM is used in combination with drugs that cause low blood sugar, such as glipizide or glyburide. This is not observed when Byetta^TM is used alone or in combination with metformin.

Recently, the FDA issued a warning linking Byetta^TM to several confirmed cases of pancreatitis. In most cases, patients had other risk factors for pancreatitis, including gallstones, severely elevated triglycerides, or alcohol use. Patients taking Byetta^TM are encouraged to contact their physician immediately if they experience severe abdominal pain with or without vomiting.

Currently, a long-acting formulation of Byetta^TM that needs administration once weekly is under investigation. A recent study of the effects of the drug at 15 weeks showed a decrease in A1C by 1 to 2 percent. Also at 15 weeks, this long-acting form was associated with weight loss of five to 11 pounds with the higher dose group; patients receiving a lower dose experienced no change in weight. In addition, 86% of patients receiving the higher dose achieved an A1C less than or equal to 7 percent at 15 weeks. Long-acting Byetta^TM was also associated with a lower rate of two-hour post-meal high blood sugar. The most frequent side effect was mild nausea. This formulation must be further evaluated by the FDA before it receives final approval for use.

Due to their modes of action, neither Januvia^TM nor Byetta^TM can be used in patients with type 1 diabetes. Dose adjustments may be necessary in patients with kidney disease. Neither drug is recommended for use in pregnancy.

As new agents, Byetta^TM and Januvia^TM are expensive medications. Each medicine is approximately $60 per month as covered by the UK health plan. Byetta^TM requires a prior-authorization by your physician before it is covered at this price. As a comparison though, for patients not having any prescription insurance, average per-month prices (based on costs at local pharmacies) are $190 for Januvia^TM, $220 to $260 for Byetta^TM, depending on the dose prescribed.

Both agents show promise for improvement in glycemic control; however, continued evaluation and longer-term studies are necessary to most accurately determine where these products fit best in treatment of diabetes. As with any medication, each of these new medicines has its own advantages and disadvantages. Therefore, it is important that both you and your diabetes care team discuss these issues before deciding to start treatment with either Januvia^TM or Byetta^TM.

Sources:
Amori RE, et al. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007; 298(2):194-06.
Byetta^TM (exenatide) injection [product information]. San Diego, CA: Amylin Pharmaceuticals, Oct 2007.
Buse JB, et al. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther. 2007; 29(1):139-53.
Januvia^TM (sitagliptin) tablets [product information]. Whitehouse Station, NJ: Merck & Co, Oct 2007.
Kim Dennis, et al. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care. 2007; 30(6):1487-93.
Lexi-Comp ONLINETM Riddle MC, et al. Exenatide elicits sustained glycaemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulphonylureas with or without metformin. Diabetes Metab Res Rev. 2006; 22(6):483-91.

Inpatient Diabetes Control