SAVOR-TIMI 53

SAVOR-TIMI 53 was a randomized, double-blind, placebo-controlled trial to assess the cardiovascular efficacy and safety of saxagliptin, a DPP-4 inhibitor, when added to standard of care in patients with type 2 diabetes mellitus.

MAIN RESULTS:
Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus

N Engl J Med. 2013 Oct 3;369(14):1317-26.

PRESENTATIONS

TIMI 53 Slides
HF Risk Stratification and Efficacy of SGLT2 Inhibitors in Patients with T2DM (Berg, ESC 2019)
SAVOR DM Genetics (Marston, AHA 2019)
A Novel Genetic Risk Score Predicts Ischemic Stroke in Patients with Cardiometabolic Disease (Patel, AHA 2020)
Clinical Applications of a Polygenic Risk Score to Predict Atrial Fibrillation in Patients with Cardiometabolic Disease (Garfinkel, AHA 2021)
A Genetic Risk Score to Predict Peripheral Artery Disease and Acute Limb Ischemia in Patients With Cardiometabolic Disease (Patel, AHA 2021)
Assessment of Atherothrombotic Risk in Patients with Type 2 Diabetes Mellitus (Berg, ACC 2022)
Development of a Novel Polygenic Risk Score to Predict Risk of Aortic Stenosis Events (Small, AHA 2022)
Genetic Predisposition To Adiposity Is Associated With Greater Risk Of Subsequent Heart Failure Events In Individuals With Type 2 Diabetes Mellitus (Moura, ACC 2023)
Risk Of Kidney Disease Progression And Efficacy Of SGLT2 Inhibition In Patients With Type 2 Diabetes Mellitus (Moura, ACC 2023)
Performance of a Polygenic Risk Score for CAD Across the Spectrum of ASCVD-An Analysis of 60k Patients from 6 TIMI Randomized Trials (Zimerman, AHA 2023)
Pathogenic cardiomyopathy gene variants inform prognosis in atrial fibrillation-results from exome sequencing in over 17,000 patients in TIMI trials (Jurgens, ESC 2024)
Exome sequencing in over 63,000 patients in TIMI trials uncovers pathogenic cardiomyopathy variant carriers with high risk for heart failure and cardiovascular death (Kany, ESC 2024)
Polygenic Risk in Heart Failure (Haller, AHA 2024)
Polygenic Risk Score Associated with Kidney Disease Progression in Patients with Cardiometabolic Disease (Park, AHA 2025)

OTHER PUBLICATIONS

The design and rationale of the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in myocardial infarction (SAVOR-TIMI) 53 study. Am Heart J. 2011 Nov;162(5):818-825.e6.

Baseline characteristics of patient population in the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus (SAVOR) – TIMI 53 Trial. Diabetes Metab Res Rev. 2013 Jul;29(5):417-26.

Incidence of pancreatitis and pancreatic cancer in a randomized controlled multicenter trial (SAVOR-TIMI 53) of the dipeptidyl peptidase-4 inhibitor saxagliptin. Diabetes Care. 2014 Sep;37(9):2435-41.

Heart Failure, Saxagliptin and Diabetes Mellitus: Observations from the SAVOR – TIMI 53 Randomized Trial. Circulation. 2014 Oct 28;130(18):1579-88.

Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Moderate or Severe Renal Impairment: Observations From the SAVOR-TIMI 53 Trial. Diabetes Care. 2015 Apr;38(4):696-705.

Impact of treatment with saxagliptin on glycaemic stability and beta-cell function in the SAVOR-TIMI 53 study. Diabetes Obes Metab. 2015 May;17(5):487-94.

Efficacy and Safety of Saxagliptin in Older Participants in the SAVOR-TIMI 53 Trial. Diabetes Care. 2015 Jun;38(6):1145-53.

Incidence of Fractures in Patients With Type 2 Diabetes in the SAVOR-TIMI 53 Trial. Diabetes Care. 2015 Nov;38(11):2142-50.

Cardiovascular Outcomes of Patients in SAVOR-TIMI 53 by Baseline Hemoglobin A1c. Am J Med. 2016 Mar;129(3):340.e1-8.

Frequency of Cancer Events with Saxagliptin in the SAVOR-TIMI 53 Trial. Diabetes Obes Metab. 2016 Feb;18(2):186-90.

Predisposing Factors for Any and Major Hypoglycemia With Saxagliptin Versus Placebo and Overall: Analysis From the SAVOR-TIMI 53 Trial. Diabetes Care. 2016 Aug;39(8):1329-37.

Prognostic Implications of Biomarker Assessments in Patients With Type 2 Diabetes at High Cardiovascular Risk: A Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2016 Dec 1;1(9):989-998.

Health-related quality-of-life implications of cardiovascular events in individuals with type 2 diabetes mellitus: A subanalysis from the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-TIMI 53 trial. Diabetes Res Clin Pract. 2017 Aug;130:24-33.

Hypoglycaemia manifestations and recurrent events: Lessons from the SAVOR-TIMI 53 outcome study. Diabetes Obes Metab. 2017 Jul;19(7):1045-1050.

Blood Pressure, Subclinical Myocardial Injury And Cardiovascular Outcomes Among Patients With Diabetes And High Cardiovascular Risk: Observations From The SAVOR-TIMI 53 Trial. Eur Heart J. 2018 Jun 21; 39(24): 2255–2262.

Cardiovascular Outcomes According to Urinary Albumin and Kidney Disease in Patients With Type 2 Diabetes at High Cardiovascular Risk: Observations From the SAVOR-TIMI 53 Trial. JAMA Cardiol. 2018 Feb 1;3(2):155-163.

Blood pressure and cardiovascular outcomes in patients with diabetes and high cardiovascular risk. Eur Heart J. 2018 Jun 21;39(24):2255-2262.

Effect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial. Diabetes Care. 2017 Jan;40(1):69-76.

Cardiac and Inflammatory Biomarkers Are Associated with Worsening Renal Outcomes in Patients with Type 2 Diabetes Mellitus: Observations from SAVOR-TIMI 53. Clin Chem. 2019 Jun;65(6):781-790.

Metformin Use and Clinical Outcomes among Patients with Diabetes with or without Heart Failure or Kidney Dysfunction: Observations from the SAVOR-TIMI 53 Trial. Circulation. 2019 Sep 17;140(12):1004-1014.

Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients with Cardiometabolic Disease. Circulation. 2021;143:470–478.

Genetic Risk Score to Identify Risk of Venous Thromboembolism in Patients with Cardiometabolic Disease. Circ Genom Precis Med. 2021 Feb;14(1):e003006.

Sex, Permanent Drug Discontinuation, and Study Retention in Clinical Trials: Insights From the TIMI trials. Circulation. 2021 Feb 16;143(7):685-695.

Causes and Risk Factors for Death in Diabetes: A Competing-Risk Analysis From the SAVOR-TIMI 53 Trial. J Am Coll Cardiol. 2021 Apr 13;77(14):1837-1840.

A Biomarker-Based Score for Risk of Hospitalization for Heart Failure in Patients With Diabetes. Diabetes Care. 2021 Nov;44(11):2573-2581

Assessing reproducibility and utility of clustering of patients with type 2 diabetes and established CV disease (SAVOR -TIMI 53 trial). PLoS One. 2021 Nov 19;16(11):e0259372. doi: 10.1371/journal.pone.0259372. eCollection 2021.

A polygenic risk score predicts atrial fibrillation in cardiovascular disease. Eur Heart J. 2023 Jan 14;44(3):221-231.

Assessment of Atherothrombotic Risk in Patients With Type 2 Diabetes Mellitus. JACC. 2023;25:2391-2402.

Risk Assessment of Kidney Disease Progression and Efficacy of SGLT2 Inhibition in Patients With Type 2 Diabetes. Diabetes Care. 2023 Oct 1;46(10):1807-1815.

Natriuretic Peptides, Body Mass Index and Heart Failure Risk: Pooled Analyses of SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61. Eur J Heart Fail 2024 Feb;26(2):260-269.

Lipoprotein(a), C-Reactive Protein, and Cardiovascular Risk in Primary and Secondary Prevention Populations. JAMA Cardiol. 2024 Apr 1;9(4):385-391.

Novel Polygenic Risk Score and Established Clinical Risk Factors for Risk Estimation of Aortic Stenosis. JAMA Cardiol. 2024 Apr 1;9(4):357-366.

Clonal hematopoiesis, cardiovascular events and treatment benefit in 63,700 individuals from five TIMI randomized trials. Nat Med. 2024 2024 Sep;30(9):2641-2647.

A Polygenic Risk Score to Predict Incident Heart Failure Across the Spectrum of Cardiovascular Risk. J Am Coll Cardiol. 2025 2025 Sep 23;86(12):860-873.

Pathogenic Cardiomyopathy-Associated Gene Variants and Prognosis in Atrial Fibrillation: Results in 18,000 Clinical Trial Participants. J Am Coll Cardiol. 2025 Sep 9;86(10):738-753.

Statistical approaches for systematically missing covariates in individual participant data meta-analysis: insights and applications using 5 large cardiovascular trials. Am J Epidemiol. 2025 Oct 9:kwaf226. doi: 10.1093/aje/kwaf226.

Polygenic Risk Score for Coronary Artery Disease Across the Spectrum of Atherosclerotic Disease. Eur J Prev Cardiol. 2025 Oct 28:zwaf693. doi: 10.1093/eurjpc/zwaf693. 

A polygenic risk score for peripheral artery disease and major adverse limb events. Eur Heart J. 2025 Nov 28:ehaf891. doi: 10.1093/eurheartj/ehaf891.

Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction. Nat Genet. 2025 Dec 19. doi: 10.1038/s41588-025-02417-6.