OBJECTIVES: to assess the cost-effectiveness of twice daily (TD) 10 μg exenatide with insulin glargine (EXE) vs once-daily (QD) liraglutide 1.2 mg or 1.8 mg both with insulin detemir (LIRA 1.2 or LIRA 1.8) in patients with type 2 diabetes mellitus (T2DM). METHODS: the Exenatide Cost-Effectiveness Model, a validated computer simulation model, was adapted to the Russian healthcare setting. Patient and intervention effects data were gathered from a clinical trials (Scott et al 2013, Buse et al 2011), comparing QD LIRA 1.2 mg, 1.8 mg and EXE 10 μg TD, as add-on to insulin glargine or detemir. The full costs were calculated for 1-st line therapy, based on published and local sources (2014). This includes the costs of drug acquisition as well as appropriate inpatient, outpatient and primary care management costs (associated with maintenance and events). In this study we simulated disease progression and treatment effects per cohort 1,000 patients for 10 years period.  RESULTS: over a simulation period, treatment with EXE vs LIRA 1.2 drove a mean increase in discounted quality-adjusted life expectancy of 0.1 (0.008; 0.015) quality-adjusted life years (QALYs), whereas therapy with EXE vs LIRA 1.8 decrease of 0.1 (-0.018; -0.011) QALYs. When compared with LIRA 1.2, EXE was the dominant strategy, i.e. less costly (-$484) and more effective. When compared to LIRA 1.8, EXE was less costly (-$1,500), but less effective. The incremental cost-effectiveness ratio (ICER) for LIRA 1.8 vs EXE was estimated at $100,941 per QALY gained, that more greater than willingness-to-pay (WTP) threshold for Russia in 2014 $36,373. In this case more cost-effective strategy was EXE with insulin glargine. CONCLUSIONS: at a WTP threshold of $36,373/QALY exenatide is likely to be a cost-effective option for the treatment of T2DM in a Russian setting.