Saxagliptin (SAXA) Efficacy and Safety in Patients With Type 2 Diabetes Mellitus (T2DM) Stratified by Cardiovascular (CV) Risk Factors

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 839-872-Diabetes & Obesity Management
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-849
William Cook*1, Brian Bryzinski1, Elsie Allen2 and Boaz Hirshberg1
1AstraZeneca, Wilmington, DE, 2Bristol-Myers Squibb, Princeton, NJ
Previous analyses of the SAXA core phase 3 program demonstrated the safety and efficacy of SAXA as monotherapy or add-on therapy for 24 weeks regardless of CV risk factors. This analysis explored the efficacy and safety of SAXA in groups stratified by hypertension (HTN), statin use, or the presence of a high (≥2) vs low (≤1) number of CV risk factors (ie, HTN, dyslipidemia, smoking, and family history of CV disease) in the following 3 regimens: SAXA+metformin (MET; n=320) vs MET (n=328) as initial therapy for 24 weeks (NCT00327015); SAXA add-on to MET (n=428) vs glipizide (GLIP) add-on to MET (n=430) for 52 weeks (NCT00575588); and SAXA (n=304) vs placebo (PBO) (n=151) as add-on to insulin (INS)±MET for 24 weeks (NCT00757588). Across studies, there were no important treatment-by-group interactions for change from baseline in A1C with HTN, statin use, or number of CV risk factors (P value range 0.07–0.98). In groups stratified by high vs low number of CV risk factors, mean change from baseline A1C was greater in patients treated with initial SAXA+MET vs PBO+MET (SAXA–PBO difference [95%CI]: high risk –0.38% [–0.68 to –0.08], low risk –0.67% [–0.91 to –0.42]) and SAXA+INS±MET vs PBO+INS±MET (high risk –0.26% [–0.50 to –0.02], low risk −0.58% [–0.83 to –0.33]) and was similar to GLIP in the SAXA+MET vs GLIP+MET study (high risk 0.08% [–0.06 to 0.22], low risk 0.10% [−0.08 to 0.28]). Similar findings were observed in groups stratified by HTN or statin use. In most groups, more patients treated with SAXA vs PBO in the initial SAXA+MET vs MET and SAXA+INS±MET studies achieved A1C <7%. In all groups, similar proportions of patients in the SAXA+MET vs GLIP+MET study achieved A1C <7%. Mean reduction from baseline body weight in all groups was greater with SAXA+MET vs GLIP+MET (SAXA–GLIP difference range, –1.9 to –2.4 kg) but was similar to PBO in the initial SAXA+MET vs MET and SAXA+INS±MET studies. The incidence of adverse events (AEs) and serious AEs was similar across treatment and CV risk groups in all studies. Confirmed hypoglycemia (symptoms plus fingerstick glucose ≤50 mg/dL) was <1% in all groups in the initial SAXA+MET vs MET study and ranged from 4.6% to 10.1% of patients receiving GLIP+MET vs 0% with SAXA+MET and from 4.0% to 7.8% with SAXA+INS±MET vs 2.5% to 8.1% with PBO+INS±MET. SAXA 5 mg/d was efficacious, with a safety profile similar to that of PBO, in patients with T2DM irrespective of concomitant HTN, statin use, or number of CV risk factors present.

Disclosure: WC: Employee, Astra Zeneca. BB: Employee, Astra Zeneca. EA: Employee, Bristol-Myers Squibb. BH: Employee, Astra Zeneca.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Supported by Bristol-Myers Squibb and AstraZeneca.