Predisposing factors for any and major hypoglycemia with saxagliptin versus placebo and overall: Analysis from the savor-TIMI 53 trial

Avivit Cahn, Itamar Raz*, Ofri Mosenzon, Gil Leibowitz, Ilan Yanuv, Aliza Rozenberg, Nayyar Iqbal, Boaz Hirshberg, Mikaela Sjostrand, Christina Stahre, Kyung Ah Im, Estella Kanevsky, Benjamin M. Scirica, Deepak L. Bhatt, Eugene Braunwald

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


OBJECTIVE: To analyze the impact of adding saxagliptin versus placebo on the risk for hypoglycemia and to identify predictors of any and major hypoglycemia in patients with type 2 diabetes included in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes (n = 16,492) were randomized to saxagliptin or placebo and followed for a median of 2.1 years. Associations between any hypoglycemia (symptomatic or glucose measurement <54 mg/dL) or major hypoglycemia (requiring extended assistance) and patient characteristics overall and by treatment allocation were studied. RESULTS: At least one hypoglycemic event was reported in 16.6% of patients, and 1.9% reported at least one major event. Patients allocated to saxagliptin versusplacebo experienced higher rates of any (hazard ratio [HR] 1.16 [95% CI 1.08, 1.25]; P < 0.001) or major (HR 1.26 [1.01, 1.58]; P = 0.038) hypoglycemia. Hypoglycemia rates (any or major) were increased with saxagliptin in patients taking sulfonylureas (SURs) but not in those taking insulin. Rates were increased with saxagliptin in those with baseline HbA1c ≤7.0% and not in those with baseline HbA1c >7.0%. Multivariate analysis of the overall population revealed that independent predictors of any hypoglycemia were as follows: allocation to saxagliptin, long duration of diabetes, increased updated HbA1c, macroalbuminuria, moderate renal failure, SUR use, and insulin use. Predictors of major hypoglycemia were allocation to saxagliptin, advanced age, black race, reduced BMI, long duration of diabetes, declining renal function, microalbuminuria, and use of short-acting insulin. Among SURs, glibenclamide was associated with increased risk of major but not any hypoglycemia. CONCLUSIONS: The identification of patients at risk for hypoglycemia can guide physicians to better tailor antidiabetic therapy.

Original languageAmerican English
Pages (from-to)1329-1337
Number of pages9
JournalDiabetes Care
Issue number8
StatePublished - 1 Aug 2016
Externally publishedYes

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Publisher Copyright:
© 2016 by the American Diabetes Association.


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