Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials

Randomized controlled trials (parallel or crossover) comparing n-3PUFAs with placebo in adults with type 2 diabetes; 2674 participants; ages 33–70; diabetes duration 1–19 years.

Omega-3 polyunsaturated fatty acids (n-3PUFAs) supplementation; total dose across trials ranged from 0.40 to 18.00 g; duration from 2 to 104 weeks; typically administered in capsule form; two trials used a sardine-enriched diet or liquid form of n-3PUFA.

n-3PUFAs produced favorable lipid-lowering effects, anti-inflammatory effects, and a small improvement in glycemic control in adults with type 2 diabetes. LDL decreased by 0.10 SD (95% CI −0.17 to −0.03; p=0.007); triglycerides −0.39 SD (−0.55 to −0.24; p<0.001); VLDL-C −0.26 SD (−0.51 to −0.01; p=0.044); VLDL-TG −0.40 SD (−0.74 to −0.06; p=0.021). HbA1c −0.27 SD (−0.48 to −0.06; p=0.010). TNF-α −0.68 SD (−1.32 to −0.03; p=0.039); IL-6 −1.67 SD (−3.14 to −0.20; p=0.026). HDL, total cholesterol, NEFA, ApoA1 and ApoB did not change significantly; CRP did not change; SBP/DBP unchanged; FPG, fasting insulin, HOMA-IR, and C-peptide not changed. Duration or dosage did not explain heterogeneity. Overall, n-3PUFAs confer modest cardiometabolic benefits in T2DM, but optimal dose and duration remain undetermined and further studies are needed.

Language bias from untranslated trials; high between-trial heterogeneity and some results sensitive to removal of individual trials; many trials short in duration (only 14/33 ≥3 months); insufficient data to separate EPA vs DHA effects; adherence data and blood fatty acid composition were not consistently reported; potential risk of bias in included trials; possible small-study effects for some outcomes.