OBJECTIVES: To assess the efficacy and safety of EU-licensed anti-diabetes agents when added to sulfonylurea (SU). METHODS: A systematic review was conducted in MEDLINE, EMBASE and CENTRAL to identify randomised controlled trials in patients with type 2 diabetes mellitus inadequately controlled by a stable dose of SU monotherapy. Direct meta-analysis, Bucher indirect comparisons and Bayesian network meta-analysis (NMA) using WinBUGs were conducted. The effect of potentially confounding baseline factors was explored through covariate analyses. RESULTS: The search identified 2,976 articles of which 2,945 were excluded based on title/abstract. On reviewing remaining full-text articles, 5 studies were selected for analysis at 24 (+/- 6) weeks follow-up. All studies were comparable in terms of baseline characteristics, including: HbA1c, age and BMI. Three classes of agents had sufficient data for meta-analysis: DPP4 inhibitors (‘DPP4s’), GLP1 analogues (‘GLP1s’) and SGLT2 inhibitors (‘SGLT2s’; only dapagliflozin has an EU licence in this class). Based on the fixed‑effect NMA, all three classes of treatment resulted in statistically significantly lower HbA1c at follow‑up compared to placebo (based on the 95% credible interval [CrI]). SGLT2 treatment resulted in significantly lower weight at follow‑up compared to placebo (‑1.54 kg; 95% CrI ‑2.16, ‑0.92), which is in contrast to treatment with GLP1s (-0.65kg; 95% CrI -1.37, 0.07) and DPP4s (0.57 kg; 95% CrI 0.09, 1.06). The odds of hypoglycaemia for SGLT2 and DPP4 add-on treatment were similar to placebo, but significantly greater than placebo for GLP1 add-on treatment (10.89; 95% CrI 4.24, 38.28). Assessment of NMA model heterogeneity was hindered by the low number of studies within the network. CONCLUSIONS: All three classes of treatments used as add-on therapy to SU provided better short-term glycaemic control compared to SU monotherapy. However, DPP4s, GLP1s and SGLT2s may show variation in terms of impact on weight and incidence of hypoglycaemia.