OBJECTIVES: To assess real-world outcomes among US employees with type 2 diabetes mellitus (T2DM) initiating insulin therapy via insulin glargine (GLA) or NPH insulin. METHODS: This retrospective analysis used MarketScan® databases to identify employees with T2DM who initiated GLA or NPH, had continuous health plan and short-term-disability (STD) coverage for 3-month pre- (baseline) and 1-year post-initiation (follow-up), were insulin-naïve but received ≥1 oral anti-diabetes drug (OAD) and/or glucagon-like peptide-1 during baseline period. Endpoints included 1-year treatment persistence (continuous study drug use without discontinuation) and adherence (adjusted medication possession ratio), hypoglycemia, healthcare utilization and costs, STD and associated cost. Observed baseline selection bias between these two cohorts was addressed by 2:1 propensity score matching (PSM).  RESULTS: A total of 534 patients (GLA: 356, NPH: 178) were matched and analyzed (women 43.8%; baseline mean age 49 year; hospitalization 15.3%; # of OADs 1.8; STD: 3.0 days). During follow-up, patients receiving GLA, comparing to NPH, were significantly more persistent and adherent (both P<0.05), had lower rates of hospitalization (23.0% vs. 31.4%; P=0.036) and endocrinologist visits (19.1% vs. 26.9%; P=0.038), similar hypoglycemia-related event rates (both 4.4%; P=1.0), higher diabetes drug costs ($1,915 vs. $1,442; P<0.001) but similar total overall healthcare costs ($13,822 vs. $15,170; P=0.488) and total diabetes-related health care costs ($4,474 vs $5,235; P=0.466). STD days and associated cost were marginally lower for GLA than NPH (16.0 vs. 24.5 days, $2,680 vs. $4,118; both P=0.086). Sensitivity analyses using 1:1 and 3:1 PSM yielded consistent results. CONCLUSIONS: This study suggested that among US employees with T2DM initiating insulin, compared to NPH, GLA was associated with improved persistence and adherence and similar direct health care cost despite higher drug costs. GLA was also associated with lower hospitalization rate, which further led to shorter STD days and associated cost, and might help improve workplace productivity.