Saxagliptin clinical trials: evaluation of CV risk

Rasalam, R., Wolf, Robert, Frederich, Robert, Fiedorek, Fred, Donovan, Mark, Harris, Susan, and Chen, Roland (2010) Saxagliptin clinical trials: evaluation of CV risk. In: [Presented at the 2010 Australian Diabetes Society Annual Scientific Meeting]. From: 2010 Australian Diabetes Society Annual Scientific Meeting, 1-3 September 2010, Sydney, NSW, Australia.

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Abstract

Diabetes is Australia's fastest growing chronic disease with approximately 890,000 patients currently diagnosed with diabetes. 1 By 2031 it is predicted that 3.3 million Australians will have type 2 diabetes mellitus, 2 thus increasing the demand for treatment. However, several diabetes, obesity, and lipid drug trials have had unexpected and unfavourable cardiovascular (CV) results. The saxagliptin (SAXA) phase 2b/3 program enrolled a range of patients with diabetes and included a controlled, long-term safety extension phase. SAXA is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor. In the SAXA clinical data, the primary endpoint, major adverse cardiovascular events (MACE; stroke, myocardial infarction or CV death, analysed post hoc) and acute cardiovascular events (ACE; acute, clinically significant events, including cardiac revascularisation procedures) were identified using selected MedDRA Preferred Terms. CV events were analysed in a comprehensive dataset: 8 randomised, double-blind, phase 2b/3 trials, which included 4607 patients (3206 randomised to SAXA 2.5, 5, or 10 mg; 150 randomised to SAXA 20, 40, or 100 mg; and 1251 randomised to placebo, metformin, or up-titrated glyburide). Overall exposure was 3758 patient-years on SAXA and 1293 patient-years on comparators. Within the SAXA population, 81% had at least 1 CV risk factor in addition to diabetes, with hypertension (52%), dyslipidaemia (44%), or history of smoking (39%) the most common; 12% had known prior CV disease. Comparator group had similar proportions. Numbers of patients with events are shown in Table. The Cox proportional hazard ratio for MACE was 0.44 (95% CI: 0.24–0.82) and for ACE was 0.59 (95% CI: 0.35–1.00). A series of sensitivity analyses using related endpoints and alternative analytic methods produced consistent results. Based on a >5000 patient-year clinical trial experience, there was no evidence of increased CV risk with SAXA treatment ― as monotherapy or in combination with other oral antidiabetic agents. These data raise the hypothesis of a cardioprotective effect of SAXA, which will be studied in the SAVOR trial.

Item ID: 50103
Item Type: Conference Item (Poster)
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Date Deposited: 06 Sep 2017 03:04
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110306 Endocrinology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1115 Pharmacology and Pharmaceutical Sciences > 111502 Clinical Pharmacology and Therapeutics @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920104 Diabetes @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
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