OBJECTIVES: Basal insulin therapy is commonly initiated in type 2 diabetes (T2DM) patients with a long-acting insulin, such as insulin glargine or the intermediate-acting insulin, NPH. In this study we evaluated the frequency of hypoglycemia associated with insulin glargine vs. NPH insulin treatment based on clinical trial results. METHODS: A systematic search was conducted in PubMed to identify clinical trials (2000-2013) in which  the efficacy and safety of insulin glargine and NPH insulin treatments were evaluated among patients with T2DM. The primary outcomes assessed in this review of clinical trial results were the frequencies of symptomatic and nocturnal hypoglycemia during trial periods. Of the 366 abstracts reviewed, 7 were of clinical trials with insulin glargine and NPH insulin treatment arms in which hypoglycemia frequency was reported. RESULTS: A total of 1,389 T2DM patients were treated with insulin glargine and 1,132 with NPH insulin. The frequency of symptomatic hypoglycemia was highly variable across the trials, ranging from 35%-96% with insulin glargine and 41%-77% with NPH insulin, as was nocturnal hypoglycemia frequency, which ranged from 13%-31% with insulin glargine and 10%-40% with NPH insulin. Two of the 7 trials reported that the frequency of symptomatic hypoglycemia was significantly less among T2DM patients treated with insulin glargine vs. NPH insulin. Of the 5 trials reporting the frequency of nocturnal hypoglycemia 4 reported it was significantly less among T2DM patients treated with insulin glargine vs. NPH insulin. Differences in the change in HbA1c during trial periods were reported as non-significant in all studies, except for 2 with morning insulin glargine arms. CONCLUSIONS: Based on clinical trial results insulin glargine and NPH insulin appear similar in glycemic efficacy, but treatment with insulin glargine may be associated with less symptomatic and nocturnal hypoglycemia than treatment with NPH insulin. Additional studies are needed to confirm these findings.