Table 2

HRs of different combinations of low HDL cholesterol and metformin use for cancer risk in type 2 diabetes

Exposuresn at riskHR (95% CI)P
HDL cholesterol <1.0 vs. ≥1.0 mmol/L
 Among metformin nonusers
  Model 1*2002.87 (1.57–5.25)0.0006
  Model 2*2002.99 (1.60–5.61)0.0006
 Among metformin users
  Model 3*2331.66 (0.72–3.87)0.2367
  Model 4*2331.61 (0.66–3.92)0.2969
 Average daily metformin dose in the whole cohort (per g)
  Model 5*1,2660.44 (0.32–0.62)<0.0001
  Model 6*1,2660.50 (0.35–0.71)<0.0001
Metformin users vs. nonusers
 Among patients with HDL cholesterol ≥1.0 mmol/L
  Model 7*1,0330.46 (0.28–0.74)0.0013
  Model 8*1,0330.51 (0.31–0.82)0.0059
 Among patients with HDL cholesterol <1.0 mmol/L
  Model 9*2330.29 (0.13–0.61)0.0013
  Model 10*2330.30 (0.13–0.70)0.0052
Biological interaction models
 Model 11*
  HDL cholesterol <1.0 mmol/L plus nonuse of metformin2006.18 (3.35–11.40)<0.0001
  HDL cholesterol ≥1.0 mmol/L plus nonuse of metformin1,1922.35 (1.47–3.75)0.0003
  HDL cholesterol <1.0 mmol/L plus use of metformin2331.83 (0.87–3.88)0.1140
  HDL cholesterol ≥1.0 mmol/L plus use of metformin1,033Reference
 Model 12*
  HDL cholesterol <1.0 mmol/L plus nonuse of metformin2005.75 (3.03–10.90)<0.0001
  HDL cholesterol ≥1.0 mmol/L plus nonuse of metformin1,1922.17 (1.35–3.49)0.0013
  HDL cholesterol <1.0 mmol/L plus use of metformin2332.02 (0.94–4.35)0.0855
  HDL cholesterol ≥1.0 mmol/L plus use of metformin1,033Reference
  • *Adjusted for LDL cholesterol–related risk indicators (LDL cholesterol ≥3.8 mmol/L and LDL cholesterol <2.8 mmol/L plus albuminuria), HDL cholesterol ≥1.30 mmol/L (not for models 7 and 8), and the nonlinear association of triglycerides with cancer.

  • †Further adjusted for age, sex, employment status, smoking status, alcohol intake, duration of diabetes, BMI (≥27.6 or <24.0 kg/m2), A1C, and SBP at enrollment and use of statins, fibrates, other lipid-lowering drugs, ACE inhibitors/ARBs, and insulin during follow-up.

  • ‡Stratified Cox model analyses on deciles of the propensity score of metformin use were included in models 5–12 to control for the likelihood of starting metformin therapy during follow-up.