Int J Clin Pract. 2009 Sep;63(9):1395-406. doi: 10.1111/j.1742-1241.2009.02143.x. Epub 2009 Jul 15.

Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial.

Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, Chen R; CV181-040 Investigators.

Collaborators (153)

Fideleff H, Maffei L, Migueles J, Sposetti G, Ulla MR, Waitman J, Chacra AR, Eliaschewitz F, Felicio J, Forti A, Gross JL, Hissa MN, Purish S, Repetto G, Saraiva JF, Sgarbi JA, Lee KF, Tong P, Adawi F, Buchs A, Cohen J, Bohem IH, Karnieli E, Klainman E, Raz I, Wainstein J, Yerushalmy Y, Aguilera M, Alvarado R, Calvo C, Gonzalez G, Gonzalez Gonzalez G, Jerjes-Sanchez C, Medina Pech CE, Robles FJ, Saldate C, Sauque Reyna L, Caballero J, Villena J, Zapata L, Zubiate C, Jasul G, Lim-Abrahan MA, Pacheco E, Tan GH, Abreu-Feshold F, Barranco Santana E, Claudio J, Vazquez Tanus JB, Ahn CW, Jang HC, Lee HC, Lee KW, Lee MK, Park JS, Woo JT, Yoo SJ, Yoon KH, Lee KO, Bernhardi D, Bhana SA, Burgess L, Chetty S, Distiller L, Kaplan H, Khutsoane DT, Moore R, Mynhardt JH, Chuang LM, Ho LT, Huang CN, Lin KC, Shih KC, Acampora MD, Adams J, Arnold G, Aventa A, Azorr M, Barrera JE, Bedel G, Bolick C, Brautigam D, Brinson AC, Catlett D, Chappel C, Chrysant S, Cohen K, Corbett B 3rd, Damian D, Dass B, Diederich CF, Doolan R, Dyck D, Eberly J, Ellis C, Ganong KD, Goldberg R, Harrison B, Hendley L, Hershberger VJ, Hoekstra JA, Hoyte S, Hurley S, Isakov T, Ison R, Jacks WP, Jain RK, Johnson D, Joiner J, Kayne D, Kayota SW, Landgarten S, Latham G, Lee FJ, Lenhard J, Lockwood RJ, Lucas KJ, McKeown-Biagas C, Mercado A, Michael B, Miller AB, Miller S, Mitchell JR, Montoro R, Morales L, Nagaria A, Norwood P Jr, Nurnberg RD, Patel M, Pearlstein P, Pearson D, Pudi KK, Rhudy J, Rigonan K, Ryan WM, Saway W, Schwartz SL, Shealy N, Sher L, Shue RG, Simon H, Sloan GK, Snyder B, Soufer J, Spence JA, Stevens JA, Sugimoto DH, Tarshis G, Trevino M, Wayne J, Weisbrot AJ, Wiegmann T, Witkin DB.

Source

Diabetes Center, Federal University of São Paulo, São Paulo, Brazil.

Erratum in

Int J Clin Pract. 2010 Jan;64(2):277.

Abstract

AIMS:

Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy.

METHODS AND PATIENTS:

A total of 768 patients (18-77 years; HbA(1c) screening >or= 7.5 to <or= 10.0%) were randomised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks. Blinded uptitration glyburide was allowed in the glyburide-only arm to a maximum total daily dose of 15 mg. Efficacy analyses were performed using ANCOVA and last-observation-carried-forward methodology.

RESULTS:

At week 24, 92% of glyburide-only patients were uptitrated to a total glyburide dose of 15 mg/day. Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide, respectively, in HbA(1c) (-0.54%, -0.64% vs. +0.08%; both p < 0.0001) and fasting plasma glucose (-7, -10 vs. +1 mg/dl; p = 0.0218 and p = 0.002). The proportion of patients achieving an HbA(1c) < 7% was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (22.4% and 22.8% vs. 9.1%; both p < 0.0001). Postprandial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide (-4296 and -5000 vs. +1196 mg.min/dl; both p < 0.0001). Adverse event occurrence was similar across all groups. Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 (13.3%) and 5 mg (14.6%) vs. uptitrated glyburide (10.1%).

CONCLUSION:

Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated.