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


Scirica BM, Bhatt DL, Braunwald E, et al; for the SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317-1326.


There was no increase in cardiovascular (CV) events with the dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin in patients with or at risk for cardiovascular disease (CVD) in SAVOR-TIMI 53 over median follow-up of 2.1 years.

Primary endpoint
The rate of the primary endpoint, a composite of CV death, nonfatal myocardial infarction (MI), or nonfatal ischemic stroke, by group:

  

Silvio E Inzucchi comments on SAVOR-TIMI 53 
  • Saxagliptin (n=8,280): 7.3% (n=613)
  • Placebo (n=8,212): 7.2% (n=609)
  • Hazard ratio, 1.0 (95% confidence interval [CI], 0.89-1.12); P=0.99 for superiority, P<0.001 for noninferiority

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-01 - SAVOR-TIMI 53 No Increase in CV Events with Saxagliptin in Patients With or At Risk for CVD 

Secondary endpoint
There was no increase in CV events with saxagliptin for the secondary endpoint, which was the primary endpoint (a composite of CV death, nonfatal MI, or nonfatal ischemic stroke) plus hospitalization for heart failure, coronary revascularization, or unstable angina. Rate of the secondary endpoint, by group:

  • Saxagliptin (n=8,280): 12.8% (n=1,059)
  • Placebo (n=8,212): 12.4% (n=1,034)
  • Hazard ratio, 1.02 (95% CI, 0.94-1.11); P=0.66

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-02 - SAVOR-TIMI No Increase in CV Events with Saxagliptin in Patients With or At Risk for 

CVD Secondary Endpoints

Hospitalization for heart failure
Saxagliptin increased hospitalization for heart failure over median follow-up of 2.1 years.

  • Saxagliptin (n=8,280): 3.5% (n=289)
  • Placebo (n=8,212): 2.8% (n=228)
  • Hazard ratio, 1.27 (95% CI, 1.07 to 1.51); P=0.007

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-03 - SAVOR-TIMI 53 Saxagliptin Increased Hospitalization for Heart Failure 

Glycemic control
Significantly better glycemic control was seen with saxagliptin treatment vs placebo. Percent of subjects with A1C <7.0% (data shown are for end of treatment; median follow-up time was 2.1 years):

  • Saxagliptin (n=8,280): 36.2% (n=2,241)
  • Placebo (n=8,212): 27.9% (n=1,832)
  • P<0.001

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-05 - SAVOR-TIMI 53 Significantly Better Glycemic Control with Saxagliptin 

Safety endpoints
A greater number of saxagliptin-treated patients had hypoglycemia vs those who received placebo. Rate of any hypoglycemia:

  • Saxagliptin (n=8,280): 15.3% (n=1,264)
  • Placebo (n=8,212): 13.4% (n=1,104)
  • P<0.001

There were similar rates of the following in both groups: pancreatitis, thrombocytopenia, lymphocytopenia, infections, hypersensitivity/skin reactions, bone fractures, and liver abnormalities.

The rate of cancer was similar between groups. There was no excess of pancreatic cancer seen with saxagliptin, and numerically more pancreatic cancers were diagnosed in placebo- treated patients (12 cases vs 5 cases in saxagliptin-treated patients; P=0.095).

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-04 - SAVOR-TIMI 53 Safety 

Endpoints

About SAVOR-TIMI 53
SAVOR-TIMI 53 was a double-blind, placebo-controlled trial examining the safety and efficacy of the DPP-4 inhibitor, saxagliptin. Subjects (N=16,492) had type 2 diabetes, A1C 6.5% to 12% and established CVD history or multiple CVD risk factors (≥1 of the following: dyslipidemia, hypertension, current smoking). Subjects were randomized 1:1 to saxagliptin (n=8,280) or matched placebo (n=8,212). Saxagliptin dose was 5 mg daily or 2.5 mg daily for patients with estimated glomerular filtration rate ≤50 ml/min. Use of other antihyperglycemic and CVD therapies was allowed. The primary endpoint was a composite of CV death, nonfatal MI, or nonfatal ischemic stroke. The secondary endpoint was the primary endpoint plus hospitalization for heart failure, coronary revascularization, or unstable angina. Median follow-up was 2.1 years.

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-06 - SAVOR-TIMI 53 Design   

Saxagliptin is not FDA approved for cardiovascular risk reduction.
SAVOR-TIMI 53=Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53

 

Related content: 

Overview: Alogliptin after acute coronary syndrome in patients with type 2 diabetes  

 

  

The pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual prescribing information for approved uses outside of the United States. 

September 2013 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

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Last Modified: 3/23/2015