Additive effects of blood glucose lowering drugs, statins and renin-angiotensin system blockers on all-site cancer risk in patients with type 2 diabetes

Table 2 Hazard ratios of drug use for cancer in patients with type 2 diabetes after excluding prevalent users for the drug in question using a non-time-dependent Cox regression model, with adjustment for co-variables, propensity score and drug use during follow-up

Users versus non-users	Sample size	Number of events	Hazard ratio (95% CI)	P
ACEIs or ARBs
Model 1	4,307	199	0.38 (0.27, 0.53)	<0.00001
Model 2	4,307	199	0.60 (0.43, 0.84)	0.0027
Model 3	4,307	199	0.55 (0.39, 0.78)	0.0009
Statins
Model 1	5,172	243	0.36 (0.24, 0.53)	<0.0001
Model 2	5,172	243	0.47 (0.32, 0.70)	0.0002
Model 3	5,172	243	0.47 (0.31, 0.70)	0.0003
Insulin
Model 1	4,639	201	0.48 (0.31, 0.73)	0.0006
Model 2	4,639	201	0.59 (0.39, 0.89)	0.0110
Model 3	4,639	201	0.58 (0.38, 0.89)	0.0119
Metformin
Model 1	2,658	129	0.38 (0.25, 0.56)	<0.0001
Model 2	2,658	129	0.39 (0.25, 0.61)	<0.0001
Model 3	2,658	129	0.39 (0.25, 0.61)	<0.0001
Sulphonylurea
Model 1	2,291	99	0.45 (0.29, 0.72)	0.0008
Model 2	2,291	99	0.44 (0.27, 0.73)	0.0013
Model 3	2,291	99	0.44 (0.27, 0.73)	0.0014
TZDs
Model 1	6,074	270	0.12 (0.03, 0.50)	0.0033
Model 2	6,074	270	0.17 (0.04, 0.69)	0.0133
Model 3	6,074	270	0.18 (0.04, 0.72)	0.0153

Model 1 adjusted for propensity scores (c-statistics = 0.80 for ACEIs or ARBs; 0.80 for statins; 0.79 for insulin; 0.73 for metformin; 0.66 for sulphonylurea; and 0.74 for TZDs), which were calculated using logistic regression procedures with age, sex, body mass index, low- and high-density lipoprotein cholesterols (LDL-C and HDL-C), triglyceride, use of tobacco and alcohol, HbA_1c, systolic blood pressure, natural log of the albumin-to-creatinine ratio, estimated glomerular filtration rate, duration of disease, peripheral arterial disease, retinopathy, neuropathy, prior myocardial infarction and stroke as independent variables. Model 2 adjusted for LDL-C-related risk indicators (that is, LDL-C <2.8 mmol/L plus albuminuria or LDL-C ≥3.8 mmol/L); non-linear associations of HDL-C and triglyceride for cancer; body mass index (<24, ≥27.6 kg/m²); age; sex; employment status; use of tobacco and alcohol; duration of disease; systolic blood pressure; and use of statins, ACEIs/ARBs, fibrates, sulphonylurea, metformin and TZDs during follow-up. Model 3 adjusted for all factors in model 2 plus the propensity score of the drug in question. No patient had been exposed to the drug in question for at least 2.5 years prior to enrolment. ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; CI, confidence interval; TZD, thiazolidinediones.

ISSN: 1741-7015