Vaccines for the prevention of seasonal influenza in patients with diabetes: systematic review and meta-analysis

Background: Patients with diabetes are at increased risk of severe influenza disease; influenza vaccination for these patients is therefore recommended by the World Health Organization and several National Immunization Technical Advisory Groups. However, no systematic review has evaluated the effects of influenza vaccines for patients with diabetes. Methods: We conducted a systematic review and meta-analysis by searching Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials. gov from inception until November 2014. We included all types of studies reporting on the efficacy, effectiveness, and/or safety of influenza vaccination in patients with type 1 and type 2 diabetes of all ages. We used the Newcastle-Ottawa scale to assess risk of bias in observational studies. Residual confounding was addressed by comparing estimates of vaccine effectiveness (VE) during influenza seasons to those obtained during off-seasons. Quality of the evidence for each outcome was assessed using the GRADE methodology. Results: Following review of 1,444 articles, 11 observational studies with a total of 170,924 participants were included. In diabetic patients of working-age (18-64 years), influenza vaccination prevented all-cause hospitalization with a pooled VE of 58% (95% CI, 6-81%) and hospitalization due to influenza or pneumonia (VE 43%; 95% CI, 28-54%), whereas no effects on all-cause mortality and influenza-like illness (ILI) were observed. In the elderly (65+), influenza vaccination prevented all-cause mortality (VE 38%; 95% CI, 32-43%), all-cause hospitalization (VE 23%; 95% CI, 1-40%), hospitalization due to influenza or pneumonia (VE 45%; 95% CI, 34-53%), and ILI (VE 13%; 95% CI, 10-16%). However, significant off-season estimates for several outcomes indicated residual confounding, particularly in elderly patients. Quality of the evidence was low to very low for all outcomes. Laboratory-confirmed influenza infections were not reported. Conclusions: Due to strong residual confounding in most of the identified studies, the available evidence is insufficient to determine the magnitude of benefit that diabetic people derive from seasonal influenza vaccination. Adequately powered randomized controlled trials or quasi-experimental studies using laboratory-confirmed influenza-specific outcomes are urgently needed.