Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Glycemic Efficacy Of Canagliflozin (Cana) By Baseline A1c And Known Duration Of Type 2 Diabetes Mellitus (T2dm) (#323)

Lawrence Blonde 1 , Lawrence A Leiter 2 , John Wilding 3 , Sonia Cerdas 4 , Cindy Tong 5 , Jacqueline Yee 5 , Gary Meininger 5
  1. Department of Endocrinology, Diabetes, and Metabolic Diseases, Ochsner Medical Center, New Orleans, LA, United States
  2. Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada
  3. Department of Obesity and Endocrinology, University of Liverpool, Liverpool, UK
  4. Hospital Cima, Centro de Investigacíon Clínica San Agustín, San José, Costa Rica
  5. Janssen Reasearch and Development, Raritan, NJ, USA

Objective: CANA is a sodium glucose co-transporter 2 (SGLT2) inhibitor with demonstrated glycemic efficacy across a range of T2DM patient populations. This analysis evaluated the effects of CANA versus placebo (PBO) on changes in A1C based on baseline A1C and duration of T2DM.

Methods: Pooled data from the 4 PBO-controlled Phase 3 studies that enrolled a general population of patients with T2DM (N = 2,313; mean age, 56.0 y; A1C, 8.0%; BMI, 32.1 kg/m2; mean known T2DM duration, 7.3 y) were analyzed. Change in A1C at 26 weeks (last observation carried forward [LOCF]) was evaluated in subgroups by baseline A1C (<8.0%, 8.0%-<9.0%, and ≥9.0%; mean baseline A1C of 7.3%, 8.4%, and 9.6%, respectively, in the total population) and T2DM duration (<5 y, 5-<10 y, and ≥10 y; mean baseline A1C of 7.9%, 8.1%, and 8.1%, respectively, in the total population). Least squares (LS) mean changes (standard error [SE]) were calculated and PBO-subtracted differences (95% confidence interval [CI]) are reported.

Results: CANA 100 and 300 mg were associated with progressively greater PBO-subtracted LS mean reductions in A1C as baseline A1C increased (A1C <8.0%: –0.45% [–0.55, –0.35] and – 0.65% [–0.74, –0.55]; A1C 8.0%-<9.0%: –0.91% [–1.07, –0.75] and –1.07% [–1.24, –0.91]; A1C ≥9.0%: –1.25% [–1.54, –0.97] and –1.48% [–1.77, –1.20], respectively). PBO-subtracted A1C reductions with CANA 100 and 300 mg were –0.70% (–0.84, –0.56) and –0.96% (–1.10, – 0.82), respectively, for patients in early stages of T2DM (<5 y). In patients with 5-<10 y T2DM duration, PBO-subtracted A1C differences were –0.74% (–0.90, –0.59) and –0.91% (–1.06, – 0.75) with CANA 100 and 300 mg, respectively; differences were –0.74% (–0.89, –0.58) and – 0.85% (–1.00, –0.70), respectively, in patients with ≥10 y T2DM duration. Overall, both CANA doses were generally well tolerated across subgroups based on baseline A1C and duration of T2DM, with a safety profile consistent with previous reports from individual studies, including increased incidences of genital mycotic infections and AEs related to osmotic diuresis with CANA compared with PBO.

Conclusion: CANA provided glycemic improvements in patients with T2DM regardless of baseline A1C or duration of T2DM. Greater reductions in A1C with CANA were seen in patients with higher baseline A1C, similar to what has been observed with other antihyperglycemic agents.