Pharmacology Update

Saxagliptin + Metformin Extended-release Tablets (Kombiglyze 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 relationship to this field of study.

The FDA has approved a second dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin combination. This follows the approval of sitagliptin/metformin in 2007. Saxagliptin and extended-release metformin XR (SAXA/MET XR) is manufactured by Bristol-Myers Squibb and marketed by Bristol-Myers Squibb and AstraZeneca as Kombiglyze™ XR.


SAXA/MET XR is indicated as adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both saxagliptin and metformin is appropriate.1


The recommended dose is 1 tablet daily with the evening meal.1 The dose should be individualized based on the patient's existing regimen and adjusted based on effectiveness and tolerability.

SAXA/MET XR is available as 5 mg/500 mg, 5 mg/ 1000 mg, and 2.5 mg/1000 mg.

Potential Advantages

SAXA/MET XR provides a once-daily regimen involving two agents with different mechanisms of action. A fixed combination reduces pill burden and may improve adherence in some patients.2

Potential Disadvantages

A fixed combination reduces the flexibility of dose titration.


SAXA/MET XR was approved based on the bioequivalence of this combination with coadministered saxagliptin and metformin HCl extended release. Clinical evidence of efficacy of this combination was based mainly on saxagliptin and immediate-release metformin.1 In a short-term, 4-week study, saxagliptin 5 mg or placebo was added to a stable dose of metformin XR in patients with type 2 diabetes (n = 93) inadequately controlled on metformin alone.3 The 24-hour mean changes in weighted glucose from baseline were 13.8 mg/mL for saxagliptin and 3.0 mg/mL for placebo. The addition of saxagliptin (5 mg) or sitagliptin (100 mg) to a stable daily dose of metformin (1500-3000 mg) resulted in similar (non-inferior) reduction in HbA1c in type 2 diabetics with baseline HbA1c between 6.5% and 10% (n = 801).4

Clinical Implications

SAXA/MET XR is the second DPP-4 inhibitor/metformin combination to be approved for marketing. The efficacy appears to be similar to sitagliptin and metformin. Metformin is considered the cornerstone of dual therapy by a consensus panel of the American Association of Clinical Endocrinologist/American College of Endocrinology.5 The DPP-4 inhibitor metformin combination is the preferred oral combination due to safety, lower risk of hypoglycemia, and weight gain relative to a sulfonylurea/metformin or thiazolidinedione/metformin combination.5


1. Kombiglyze XR prescribing Information. Princeton, NJ: Bristol-Myers Squibb Company; November 2010.

2. Xhernthaner G. Fixed-dose combination therapies in the management of hyperglycaemia in Type 2 diabetes. Diabet Med 2010;27:739-743.

3. Stenlof K et al. Saxagliptin and metformin XR combination therapy provides glycemic control over 24 hours in patients with T2DM inadequately controlled with metformin. Curr Med Res Opin 2010;26:2355-2363.

4. Scheen AJ. Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus. Diabetes Metab Res Rev 2010;26:540-549.

5. Rodbard HW et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus. Endocr Pract 2009;15:540-559.