OBJECTIVES: Collect randomized clinical evidence on the efficacy and safety of anti-diabetic agents used in dual or triple therapy or add-on to insulin to provide a qualitative overview of the available evidence and undertake a meta-analysis.  METHODS: A SLR was conducted in line with NICE guidelines to identify randomised controlled trials assessing agents received in combination with metformin (MET), a sulphonylurea (SU), MET+SU, MET+pioglitazone, or insulin. Interventions of interest included SGLT-2 inhibitors (canagliflozin and dapagliflozin), sulphonylureas, pioglitazone, DDP-4 inhibitors, GLP-1 analogues and insulin. Electronic searches were undertaken using Medline, Medline-in-process, Embase, and the Cochrane Library and supplemented with hand searches. An ad hoc search was conducted to identify the most recent data at 104 weeks.  RESULTS: A total of 159 clinical trials met inclusion criteria. The frequency of studies by background therapy was as follows: MET (38%), mixed (trials containing treatment arms with different background therapies; 25%), insulin (21%), MET+SU (9%), and SU alone (8%). One study (assessing canagliflozin) featured a background of MET+pioglitazone.  Studies varied in terms of treatment duration (12 to 104 weeks), presence and duration of run-in periods (57% studies with run-in, from 0.7 to 18 weeks), HbA1c eligibility criteria (minimum from 6% to 7%), body mass index (BMI; 37 studies focused on overweight and obese patients, two studies focused on obese patients) and age for inclusion (from ≥18 to ≤ 85 years). CONCLUSIONS: The outcome of this SLR will serve as input-data in a meta-analysis, to assess relative efficacy of T2DM treatments in different background therapy settings.