Sitagliptin and Metformin Extended-Release Tablets (Janumet® XR)
Pharmacology Update
Sitagliptin and Metformin Extended-Release Tablets (Janumet® XR)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved an extended-release, once-daily, dipeptidyl-4 (DPP-4) inhibitor in combination with metformin for adults with type 2 diabetes. Janumet XR combines sitagliptin and metformin. The new combination is the second such product joining Kombiglyze XR, which combines saxagliptin and metformin. Janumet XR is marketed by Merck & Co., Inc.
Indications
Sitagliptin and metformin extended-release tablets (SIT/MET ER) are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both sitagliptin and extended-release metformin is appropriate.1
Dosage
The starting dose of SIT/MET XR should be individualized based on the patient's existing dosages and maintaining the same total daily dose of sitagliptin and metformin.1 The dose may be titrated up to 100 mg of sitagliptin and 2000 mg of extended-release metformin. The dose should be taken once daily, preferably with the evening meal.
SIT/MET XR is available as 50 mg/500 mg, 50 mg/1000 mg, and 100 mg/1000 mg tablets.
Potential Advantages
SIT/MET XR provides a once-daily formulation involving two drugs with different and complementary mechanisms of action. Fixed-combination medications reduce pill burden and may improve adherence in some patients.2
Potential Disadvantages
There have been postmarketing reports of worsening renal function in patients taking sitagliptin with or without metformin as well as reports of acute pancreatitis.1 The fixed combination limits the flexibility of dose titration.
Comments
As with the combination of saxagliptin and metformin XR, SIT/MET XR was also approved based on bioequivalence of the fixed combinations and coadministration of the individual drugs.1,3 There were no clinical studies conducted with SIT/MET XR per se. The combination of SIT/MET XR provides greater HbA1c reduction than either agent alone. In a double-blind, placebo-controlled, 24-week study as initial treatment in type 2 diabetics with a mean baseline HbA1c of 8.8%, sitagliptin 100 mg and metformin 2000 mg daily showed a placebo-adjusted reduction of HbA1c of 2.1%, (95% confidence interval [CI], -2.3, -1.8) compared to sitagliptin, -0.8% (CI, -1.1, -0.6) and metformin, -1.3% (CI, -1.5, -1.1).1,4 The addition of sitagliptin 100 mg to patients inadequately controlled on metformin doses of at least 1500 mg daily produced a placebo-adjusted reduction -0.7% (CI, -0.8, -0.5) in HbA1c.1
Clinical Implications
SIT/MET XR is the second extended-release formulation of a DPP-4 inhibitor and metformin. There are no known advantages of the combination over the saxagliptin/metformin XR formulation. The consensus panel of the American Association of Clinical Endocrinologists/American College of Endocrinology stated that these combinations are preferable to sulfonylurea/metformin or thiazolidinedione/metformin in patients at risk for hypoglycemia and/or weight gain.5 DPP-4/metformin combinations provide benefit similar to sulfonylurea/metformin in lowering postprandial glucose but less benefit in lowering fasting glucose levels.5
References
1. Janumet XR Prescribing Information. Whitehouse Station, NJ: Merck & Co., Inc; February 2012.
2. Schernthaner G. Diabet Med 2010;27:739-743.
3. Migoya EM, et al. Clin Drug Investig 2010;30:855-866.
4. Goldstein BJ, et al. Diabetes Care 2007;30:1979-1987.
5. Rodbard HW, et al. Endocr Pract 2009;15:540-559.
The FDA has approved an extended-release, once-daily, dipeptidyl-4 (DPP-4) inhibitor in combination with metformin for adults with type 2 diabetes. Janumet XR combines sitagliptin and metformin. The new combination is the second such product joining Kombiglyze XR, which combines saxagliptin and metformin. Janumet XR is marketed by Merck & Co., Inc.Subscribe Now for Access
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