Systematic Review and Meta-analysis of Randomized Controlled Trials of the Effect of Fish Oil Supplementation on Cardiovascular Outcomes in Diabetes

Background: Cardiovascular disease (CVD) accounts for a large proportion of annual deaths around the world. In both the general population as well as in high-risk subgroups, achieving a healthy diet is one approach to lower the risk for CVD. Fish oil supplements have been widely investigated for cardiovascular indications, showing consistent reductions in triglycerides with variable effects on other intermediate risk factors (glycemia, blood pressure, inflammation) which have not translated into reductions in patient-important clinical outcomes. Recent systematic reviews and meta-analyses of the available randomized trials have failed to show a meaningful cardiovascular benefit of fish oil supplementation. It is unclear whether this lack of benefit holds across all groups, especially groups with a high triglyceride phenotype and at high cardiovascular risk such as those with diabetes. No systematic review and meta-analysis has specifically synthesized the evidence of the effect of fish oil supplementation on cardiovascular outcomes in people with diabetes. On the basis of several recent large cardiovascular outcomes trials in people with diabetes or that included subgroups of people with diabetes, the 2019 American Diabetes Association and 2018 Diabetes Canada clinical practice guidelines recommended against the use of fish oil supplementation for cardiovascular risk reduction in people with diabetes. The European Association for the Study of Diabetes (EASD) have made a similar recommendation but have not updated their clinical practice guidelines since 2004. To inform the update of the EASD clinical practice guidelines for nutrition therapy, the Diabetes and Nutrition Study Group (DNSG) of the EASD has commissioned a series of evidence syntheses. The proposed systematic review and meta-analysis of randomized controlled trials will assess the effect of fish oil supplementation on cardiovascular outcomes in people with diabetes and use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence.

Need for proposed research: There is an urgent need for a synthesis of the evidence of the effect of fish oil supplementation on cardiovascular outcomes in people with diabetes to inform the update of the EASD clinical practice guidelines for nutrition therapy. High quality systematic reviews and meta-analyses of randomized controlled trials with assessment of the certainty of the evidence using GRADE provide the strongest form of evidence synthesis to support clinical practice guidelines and public health policy development.

Objective: To inform the update of the European Association for the Study of Diabetes (EASD) clinical practice guidelines for nutrition therapy, the investigators will conduct a systematic review and meta-analysis of randomized controlled trials of the effect of fish oil supplementation on cardiovascular outcomes in people with diabetes and use the GRADE approach to assess the certainty of the evidence.

Design: The planning and conduct of the proposed meta-analyses will follow the Cochrane handbook for systematic reviews of interventions. The reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Data sources: MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials databases will be searched using appropriate search terms supplemented by hand searches of references of included studies.