Chronic complication risk and benefits of fenofibrate in type 2 diabetes by a PPARα polymorphism (rs6008845, C/T): a FIELD trial substudy

Januszewski, AS; Huang, MLH; Mangani, AS; Ong, KL; Dalton, C; O'Connell, RL; Li, L; Sullivan, DR; Strbenac, D; Donoghoe, MW; Brown, C; Carroll, LM; Gebski, V; Scott, RS; John Simes, R; Jenkins, AJ; Keech, AC; FIELD trial investigators

doi:10.1016/j.diabres.2026.113168

Type 2 & other diabetes

Chronic complication risk and benefits of fenofibrate in type 2 diabetes by a PPARα polymorphism (rs6008845, C/T): a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial substudy

Diabetes Res Clin PractPublished 21 Feb 2026Secondary analysis of the FIELD randomised trial

Primary result · Microvascular complicationsResultHazard ratio 1.15 95% CI 1.01–1.31

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Authors' conclusion

PPARα rs6008845 T allele was associated with a higher risk of microvascular complications and cancer death. Fenofibrate showed consistent vascular protection irrespective of PPARα genotype.

Study context

Population: Adults with T2D in the FIELD study genotyped for PPARα rs6,008,845genotyped
Participants: 8,159 adults

Comparison: PPARα rs6008845 genotypes; fenofibrate vs placebo by genotype
Primary endpoint: Chronic complications (microvascular, macrovascular) and death
Follow-up: median 5-year follow-up

Methodological detailsgenetic substudy

Genetic substudy

Primary result

Microvascular complications

Hazard ratio

1.15

95% CI 1.01–1.31

P = 0.041

T/Tvs C/C

HR 1.15 (95% CI 1.01–1.31); P = 0.041

As reported in the abstract

Further findings

Any vascular complication, per T allele

HR per T allele: 1.06 (1.00-1.12), p = 0.029

Non-CVD-related mortality, per T allele

HR per T allele: 1.18 (1.01-1.36), p = 0.032

Cancer-related mortality, per T allele

HR per T allele: 1.19 (1.01-1.41), p = 0.041
Significant genotype-by-dyslipidemia interaction under the atherogenic dyslipidemia definition

Fenofibrate effect on microvascular, macrovascular and composite vascular events

Fenofibrate reduced events, HR range (all p < 0.02): 0.79-0.87
No evidence of treatment-by-genotype interaction

Events during follow-up (whole cohort) · median 5-year follow-up

Chronic complications: 2,931 (35.9%)
Microvascular events: 2,004 (24.6%)
Macrovascular events: 1,359 (16.7%)

Original publication

Chronic complication risk and benefits of fenofibrate in type 2 diabetes by a PPARα polymorphism (rs6008845, C/T): a FIELD trial substudy. Diabetes Res Clin Pract. Published 21 February 2026. doi:10.1016/j.diabres.2026.113168

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