Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin: Results From the SEARCH Database

Purpose

To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men.

Patients and Methods

Data of 843 diabetic men who underwent RP were stratified on the basis of preoperative use of no drug or of metformin, statin, or both. Multivariable Cox models were used to test the association between treatment and BCR. In a secondary analysis, models were stratified by race and body mass index (BMI) and further adjusted for glycated hemoglobin (HbA1c).

Results

A total of 259 men (31%) received statin therapy, 94 (11%) metformin, 307 (36%) metformin + statin, and 183 (22%) neither. Five-year BCR-free survival rates were 75% in metformin only versus 75% in metformin + statin versus 60% in statin versus 68% in no drug groups (log-rank, P = .003). On multivariable analysis, preoperative statin use was associated with increased BCR risk versus men receiving neither drug (hazard ratio [HR] = 1.84; 95% confidence interval [CI], 1.28-2.64). Metformin alone (HR 0.88; 95% CI, 0.53-1.47) and metformin + statin (HR 0.88; 95% CI, 0.58-1.33) were unrelated to BCR risks. In secondary analysis, the association between statin use and higher BCR risk was similar regardless of race, but was stronger among men with BMI ≥ 30 kg/m² (HR 3.12; 95% CI, 1.70-5.72). These results were largely unchanged after adjusting for HbA1c.

Conclusion

Among diabetic men undergoing RP, preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin. If validated in future findings, research is needed to understand the basis for these associations.