Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Feb 24:14:17.
doi: 10.1186/1472-6823-14-17.

A randomized controlled trial of the efficacy and safety of twice-daily saxagliptin plus metformin combination therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy

Judith L White  1 , Patricia Buchanan, Jia Li, Robert Frederich
Affiliations

A randomized controlled trial of the efficacy and safety of twice-daily saxagliptin plus metformin combination therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy

Judith L White et al. BMC Endocr Disord. .

Abstract

Background: To compare the safety and efficacy of saxagliptin 2.5 mg twice daily (BID) versus placebo add-on therapy to metformin immediate release (IR) in patients with type 2 diabetes and inadequate glycemic control with metformin alone.

Methods: This multicenter, 12-week, double-blind, parallel-group trial enrolled adult outpatients with type 2 diabetes (glycated hemoglobin [HbA1c] 7.0%-10.0%) on stable metformin IR monotherapy (≥1500 mg, BID for ≥8 weeks). Patients were randomized to double-blind saxagliptin 2.5 mg BID or placebo added on to metformin IR following a 2-week, single-blind, placebo add-on therapy lead-in period. The primary end point was the change from baseline to week 12 in HbA1c. Key secondary end points included change from baseline to week 12 in fasting plasma glucose (FPG) and the proportion of patients achieving HbA1c <7.0% or HbA1c ≤ 6.5% at week 12. Efficacy was analyzed in all patients who received randomized study drug with ≥1 postbaseline assessment. Safety was assessed in all treated patients.

Results: In total, 74 patients were randomized to double-blind saxagliptin add-on therapy and 86 to placebo add-on therapy. At week 12, least-squares mean changes (95% CI) from baseline HbA1c (adjusted for baseline HbA1c) were significantly greater (P = 0.006) in the saxagliptin + metformin group -0.56% (-0.74% to -0.38%) versus the placebo + metformin group -0.22% (-0.39% to -0.06%). Adjusted mean changes from baseline in FPG were numerically greater with saxagliptin versus placebo; the difference (95% CI) -9.5 mg/dL (-21.7 to 2.7) was not statistically significant (P = 0.12). A numerically greater proportion of patients in the saxagliptin group than the placebo group achieved HbA1c < 7.0% (37.5% vs 24.2%) or HbA1c ≤6.5% (24.6% vs 10.7%). There were no unexpected safety findings. Hypoglycemia occurred in 4 patients (5.4%) in the saxagliptin group and 1 patient (1.2%) in the placebo group; confirmed hypoglycemia (symptoms plus fingerstick glucose ≤50 mg/dL) occurred in 1 patient in the placebo group.

Conclusions: Addition of saxagliptin 2.5 mg BID to metformin therapy in patients with type 2 diabetes and inadequate glycemic control on metformin monotherapy reduced HbA1c compared with placebo added to metformin, with an adverse events profile similar to placebo and no unexpected safety findings.

Trial registration: ClinicalTrials.gov NCT00885378.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Patient disposition. *Did not satisfy study inclusion and exclusion criteria. †Abdominal pain secondary to partial small bowel obstruction (later classified as a serious AE, requiring hospitalization). ‡Values did not meet the exclusion criteria; however, the investigator chose to withdraw the patient for safety reasons.
Figure 2
Figure 2
Mean change from baseline HbA1c and fasting plasma glucose (FPG). A. Mean (SE) change from baseline HbA1c during the double-blind treatment period. BID = twice daily; HbA1c = glycated hemoglobin; SAXA = saxagliptin. Mean (SE) baseline values were 7.92% (0.11) in the saxagliptin group and 7.97% (0.09) in the placebo group. B. Mean (SE) change from baseline fasting plasma glucose (FPG) during the double-blind treatment period. BID = twice daily; FPG = fasting plasma glucose; SAXA = saxagliptin. Mean (SE) baseline values were 164.22 mg/dL (5.51) in the saxagliptin group and 161.25 mg/dL (4.62) in the placebo group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zinman B. Initial combination therapy for type 2 diabetes mellitus: is it ready for prime time? Am J Med. 2011;124(1 Suppl):S19–S34. - PubMed
    1. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care. 2012;35(6):1364–1379. doi: 10.2337/dc12-0413. - DOI - PMC - PubMed
    1. Global guideline for type 2 diabetes. http://www.staff.ncl.ac.uk/philip.home/IDF%20GGT2D.pdf.
    1. Handelsman Y, Mechanick JI, Blonde L, Grunberger G, Bloomgarden ZT, Bray GA, Dagogo-Jack S, Davidson JA, Einhorn D, Ganda O, Garber AJ, Hirsch IB, Horton ES, Ismail-Beigi F, Jellinger PS, Jones KL, Jovanovič L, Lebovitz H, Levy P, Moghissi ET, Orzeck EA, Vinik AI, Wyne KL. American Association of Clinical Endocrinologists medical guidelines for clinical practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17(2 Suppl):1–53. - PubMed
    1. Blonde L, San Juan ZT. Fixed-dose combinations for treatment of type 2 diabetes mellitus. Adv Ther. 2012;29(1):1–13. doi: 10.1007/s12325-011-0094-1. - DOI - PubMed

Associated data

LinkOut - more resources

  NODES
Association 3
twitter 2