Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial
Article Figures & Tables
Figures
- Figure 1
Selection criteria for the study population in the CPRD.
- Figure 2
Multivariable-adjusted HRs and 95% CIs for the association between initiators of metformin monotherapy and initiators of sulfonylurea monotherapy and cancer risk using the ITT principle in the CPRD. NHL, non-Hodgkin lymphoma.
- Figure 3
Proportion of participants who adhered to their initial antidiabetes treatment in the CPRD.
- Figure 4
Multivariable-adjusted HRs and 95% CIs for the association between initiators of metformin monotherapy and initiators of sulfonylurea monotherapy and total cancer risk using the ITT principle in the CPRD by type of sensitivity analyses. (Sensitivity analysis 1: after excluding participants with any treatment breaks of more than 90 days during the initial qualifying 12-month exposure period. Sensitivity analysis 2: after redefining the exposure to an antidiabetes drug class based on the first 6 months of each participant's prescription record compared with the 12-month treatment period used in the primary analysis. Sensitivity analysis 3: after excluding participants with any treatment breaks of more than 90 days during the latter qualifying 6-month exposure period. Sensitivity analysis 4: after excluding the initial 36 months of follow-up after the first antidiabetes prescription).
- Figure 5
Multivariable-adjusted HRs and 95% CIs for the association between initiators of metformin monotherapy and initiators of sulfonylurea monotherapy and total cancer risk using the ITT principle in the CPRD by subgroups.
Tables
- Table 1
Baseline characteristics by antidiabetes treatment in the CPRD
Metformin mono-tx Metformin combo-tx Sulfonylurea mono-tx TZDs mono-tx Other OHA mono-tx Other OHA combo-tx Insulin mono-tx Insulin combo-tx n = 51,484 n = 20,967 n = 18,264 n = 292 n = 263 n = 426 n = 1,723 n = 2,401 Sex Male 28,893 (56.1) 11,437 (54.6) 10,578 (57.9) 170 (58.2) 156 (59.3) 246 (57.7) 979 (56.8) 1,330 (55.4) Female 22,591 (43.9) 9,530 (45.4) 7,686 (42.1) 122 (41.8) 107 (40.7) 180 (42.3) 744 (43.2) 1,071 (44.6) Age, years 35–49 9,024 (17.5) 4,329 (20.7) 1,901 (10.4) 38 (13.0) 45 (17.1) 71 (16.7) 547 (31.8) 767 (31.9) 50–64 22,086 (42.9) 9,120 (43.5) 6,327 (34.6) 120 (41.1) 111 (42.2) 162 (38.0) 641 (37.2) 941 (39.2) 65–79 17,616 (34.2) 6,503 (31.0) 7,946 (43.5) 112 (38.4) 91 (34.6) 160 (37.6) 469 (27.2) 609 (25.4) ≥80 2,758 (5.4) 1,015 (4.8) 2,090 (11.5) 22 (7.5) 16 (6.1) 33 (7.7) 66 (3.8) 84 (3.5) BMI, kg/m2 <18.5 46 (0.1) 36 (0.2) 124 (0.7) 2 (0.7) 3 (1.1) 3 (0.7) 11 (0.6) 37 (1.5) 18.5–24.9 4,037 (7.8) 2,112 (10.1) 4,435 (24.3) 49 (16.8) 42 (16.0) 125 (29.3) 306 (17.8) 563 (23.5) 25–29.9 16,321 (31.7) 6,485 (30.9) 6,797 (37.2) 105 (36.0) 103 (39.2) 142 (33.3) 460 (26.7) 638 (26.6) ≥30 29,098 (56.5) 11,024 (52.6) 3,833 (21.0) 128 (43.8) 94 (35.7) 109 (25.6) 468 (27.2) 932 (38.8) Unknown 1,982 (3.9) 1,310 (6.2) 3,075 (16.8) 8 (2.7) 21 (8.0) 47 (11.1) 478 (27.7) 231 (9.6) Smoking Never 21,214 (41.2) 8,052 (38.4) 6,514 (35.7) 135 (46.2) 93 (35.4) 168 (39.4) 547 (31.8) 811 (33.8) Former 18,225 (35.4) 7,075 (33.7) 4,194 (23.0) 108 (37.0) 57 (21.7) 118 (27.7) 379 (22.0) 734 (30.6) Current 8,389 (16.3) 3,545 (16.9) 2,53 (13.8) 42 (14.4) 41 (15.6) 56 (13.2) 283 (16.4) 516 (21.5) Unknown 3,656 (7.1) 2,295 (11.0) 5,026 (27.5) 7 (2.4) 72 (27.3) 84 (19.7) 514 (29.8) 340 (14.1) Alcohol Never 8,547 (16.6) 3,638 (17.4) 2,868 (15.7) 45 (15.4) 45 (17.1) 71 (16.7) 215 (12.5) 390 (16.2) Former 1,426 (2.8) 575 (2.7) 283 (1.6) 6 (2.0) 4 (1.5) 10 (2.3) 50 (2.9) 95 (3.9) Current 29,427 (57.1) 10,641 (50.7) 8,056 (44.1) 169 (57.9) 129 (49.1) 190 (44.6) 595 (34.5) 1,108 (46.2) Unknown 12,084 (23.5) 6,113 (29.2) 7,057 (38.6) 72 (24.7) 85 (32.3) 155 (36.4) 863 (50.1) 808 (33.7) Aspirin/NSAID use* No 20,414 (39.7) 9,027 (43.0) 9,333 (51.1) 114 (39.0) 136 (51.7) 211 (49.5) 889 (51.6) 1,057 (44.0) Sparse 13,391 (26.0) 5,829 (27.8) 4,354 (23.8) 65 (22.3) 69 (26.2) 110 (25.8) 419 (24.3) 717 (29.9) Medium 11,382 (22.1) 4,064 (19.4) 3,124 (17.1) 74 (25.3) 31 (11.8) 75 (17.6) 319 (18.5) 423 (17.6) Frequent 6,297 (12.2) 2,047 (9.8) 1,453 (8.0) 39 (13.4) 27 (10.3) 30 (7.1) 96 (5.6) 204 (8.5) Statin use* No 19,352 (37.6) 9,709 (46.3) 13,422 (73.5) 81 (27.7) 178 (67.7) 249 (58.5) 1,125 (65.3) 1,238 (51.6) Sparse 10,783 (20.9) 4,651 (22.2) 1,758 (9.6) 74 (25.3) 28 (10.6) 66 (15.5) 283 (16.4) 585 (24.4) Medium 13,54 (26.3) 4,334 (20.7) 1,991 (10.9) 79 (27.1) 27 (10.3) 79 (18.5) 233 (13.5) 397 (16.5) Frequent 7,809 (15.2) 2,273 (10.8) 1,093 (6.0) 58 (19.9) 30 (11.4) 32 (7.5) 82 (4.8) 181 (7.5) Hormone use*† No 19,193 (85.0) 7,830 (82.2) 6,841 (89.0) 106 (86.9) 91 (85.0) 149 (82.8) 624 (83.9) 821 (76.7) Sparse 1,289 (5.7) 633 (6.6) 316 (4.1) 5 (4.1) 5 (4.7) 10 (5.6) 54 (7.3) 89 (8.3) Medium 1,389 (6.1) 697 (7.3) 341 (4.4) 6 (4.9) 8 (7.5) 16 (8.9) 52 (6.9) 115 (10.7) Frequent 720 (3.2) 370 (3.9) 188 (2.5) 5 (4.1) 3 (2.8) 5 (2.7) 14 (1.9) 46 (4.3) Diabetes duration, days‡ Median (IQR) 99 (1–618) 35 (0–360) 54 (0–414) 259 (5–868) 206 (6–765) 30 (0–347) 18 (0–105) 30 (0–347) Missing, % 5.6 8.1 17.0 9.2 14.8 15.6 39.0 8.7 First year of therapy Median (IQR) 2005 (2003–2007) 2004 (2001–2007) 2000 (1996–2002) 2005 (2004–2006) 2000 (1998–2003) 2002 (1999–2004) 2001 (1997–2004) 2004 (2001–2007) Figures are n (%) unless otherwise specified. Combo-tx, combination therapy; IQR, interquartile range; mono-tx, monotherapy; TZDs, thiazolidinediones.
↵*Based on the percentile distribution of the number of prescriptions as no use, sparse use (1–10% of all prescriptions), medium use (10–50% of all prescriptions), and frequent use (>50% of all prescriptions). The exact distributional cut points were use of aspirin or NSAIDs: no, sparse [1–5 prescriptions], medium [6–16 prescriptions], frequent use [>16 prescriptions]; use of statins: no, sparse [1–6 prescriptions], medium [7–15 prescriptions], frequent use [>15 prescriptions]; use of exogenous hormones in women: no, sparse [1–2 prescriptions], medium [3–7 prescriptions], frequent use [>7 prescriptions].
↵†Exogenous hormone use (oral contraceptives and hormone replacement therapy) in women.
↵‡From time of diabetes diagnosis to time of first antidiabetes treatment prescription.
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