OBJECTIVES: This study compared hypoglycemia rates in patients with type 2 diabetes on metformin who augmented treatment with saxagliptin or glipizide 5-20 mg/day.  METHODS: This retrospective analysis utilized US healthcare claims data from the Truven Health MarketScan Research Databases. Data were from adults on metformin monotherapy who added saxagliptin or glipizide 5-20 mg/day between 1 August 2009 and 31 December 2010. Hypoglycemia event rates were compared during the 4 months after initiation of saxagliptin or glipizide. A hypoglycemia event was defined as a diagnosis of hypoglycemia on an outpatient or emergency room claim, a principal diagnosis on a hospital claim, or a glucagon injection in an outpatient setting. Analyses were adjusted for patient demographics and clinical characteristics using inverse propensity score weights and rate ratios were computed using bivariate Poisson regression. To achieve maximal covariate balance in adjusted analyses, only patients with a propensity score ≥0.02 were retained for analysis.  RESULTS: A total of 9,246 patients (1,567 taking saxagliptin; 7,679 taking glipizide) qualified. During 120 days of follow-up, there were 205 hypoglycemia events. Most of the hypoglycemia events (93.2%) occurred in the outpatient setting. There were no inpatient or emergency room hypoglycemia events in the saxagliptin cohort. The overall unadjusted rate of hypoglycemia was significantly lower in the saxagliptin cohort than in the glipizide cohort (1.74 vs. 7.73 per 100 person-years; p<0.001; rate ratio=0.23 [95% confidence interval=0.10-0.44]). After applying inverse propensity score weights (N=8,241), the adjusted rate of hypoglycemia also was significantly lower in the saxagliptin cohort versus the glipizide cohort (1.74 vs. 4.18 per 100 person-years; p=0.002; rate ratio=0.42 [95% confidence interval=0.24-0.71]).  CONCLUSIONS: Treatment with saxagliptin was associated with a lower risk of hypoglycemia compared with glipizide 5-20 mg/day in a real-world database.  These results add confidence to similar findings from clinical trials.