OBJECTIVES:  Adequate resuspension of insulins that require it is important for safe and efficacious insulin administration. The aim of this study was to investigate the clinical, economic and patient burden of resuspension in patients with insulin-treated diabetes. METHODS: A systematic search of databases, congress material and grey literature was supplemented with review of the selected articles’ bibliographies. RESULTS: Of 5035 articles identified, six studies met eligibility criteria; all investigated clinical outcomes of IIR. Observational studies either measured optical density of insulin or used patient-reported adherence to protocol to assess resuspension. All reported IIR, but varied from 35% (no mixing) to 99% (not following protocol). In three studies IIR resulted in insulin dosing inaccuracy. In one study, IIR resulted in significant pharmacokinetic/pharmacodynamic differences. IIR of vertically maintained pens resulted in shorter (tip up) or longer (tip down) duration of NPH action compared with properly resuspended insulin (9.4 [SD 1.7], 15.4 [2.3] vs 11.8 hours [2.6], p<0.05; respectively). IIR was also linked to greater variability in glucose infusion rate and plasma insulin concentrations. Correlations between IIR and poor glycaemic control were reported in three studies, but none were significant. In one study, patients who reduced IIR following education had a significantly lower rate of hypoglycaemic events per month vs prior to education (0.4 [0.1] vs 1.0 [0.3], p<0.05), while their HbA remained similar to baseline. CONCLUSIONS: The complexity of adequate insulin resuspension may require additional resources to provide patient education. The heterogeneity of this small data set limits the generalizability of the results but highlights the consequences IIR can have on clinical outcomes. No studies investigated the impact of IIR on patient burden or health-related quality of life. Thus, further research is needed to close the gaps in knowledge of this important step in insulin administration.