Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.

By B. Scirica, Deepak L. Bhatt, E. Braunwald, P. Steg, J. Davidson, B. Hirshberg, P. Ohman, R. Frederich, S. Wiviott, Elaine B. Hoffman and 8 more. New England Journal of Medicine, 2013

3,241 citations recorded by the source corpus.

BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. METHODS We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years. Physicians were permitted to adjust other medications, including antihyperglycemic agents. The primary end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P=0.99 for superiority; P<0.001 for noninferiority); the results were similar in the "on-treatment" analysis (hazard ratio, 1.03; 95% CI, 0.91 to 1.17). The major secondary end point of a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group (12.8% and 12.4%, respectively, according to 2-year Kaplan-Meier estimates; hazard ratio, 1.02; 95% CI, 0.94 to 1.11; P=0.66). More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio, 1.27; 95% CI, 1.07 to 1.51; P=0.007). Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups (acute pancreatitis, 0.3% in the saxagliptin group and 0.2% in the placebo group; chronic pancreatitis, <0.1% and 0.1% in the two groups, respectively). CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. (Funded by AstraZeneca and Bristol-Myers Squibb; SAVOR-TIMI 53 ClinicalTrials.gov number, NCT01107886.).

Subfields: Endocrinology, Diabetes and Metabolism, Surgery

View Paper: https://www.semanticscholar.org/paper/3ac29b634246f354fa1685db07e3ae4b89d18207

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrinology, Diabetes and Metabolism

In Surgery

Citations in the corpus

Diabetic vascular diseases: molecular mechanisms and therapeutic strategies (2023, background): “Although GLP-1RA and dipeptidyl peptidase-4 inhibitors (DPP-4i) also confer some cardiovascular benefits, they do not offer a significant advantage for reducing the hospitalization of HF in patients with diabetes (Table 1).(43,44,45)”
Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes (2015, background): “Dipeptidyl peptidase 4 inhibitors One large trial involving the dipeptidyl peptidase 4 (DPP-4) inhibitor saxagliptin found no overall cardiovascular risk or benefit (although the follow-up was only slightly more than 2 years) compared with placebo [28].”
GLP-1 receptor agonists in the treatment of type 2 diabetes – state-of-the-art (2020, neutral): “SUSTAIN-6 (subcutaneous semaglutide) [100], 2: PIONEER-6 (oral semaglutide) [101], 3: natide) [97], 6: ELIXA (lixisenatide) [95], 7: EMPA-REG Outcomes (empagliflozin) [120], 8: VERTIS-CV (ertugliflozin, presented at the 80th scientific session of the American Diabet SAVOR-TIMI-53 (saxagliptin) [125]”