Table 3.
Nonexhaustive summary of associations between the use of hypoglycemic medications (insulin, insulin analogs, metformin, thiazolidinediones, sulfonylurea, and α-glucosidase inhibitor) and the risk of CRC.
| Agent categories | Ref. | Design | Main findings |
|---|---|---|---|
| Insulin and its analogs | Ma et al. [96] | Cohort study (n = 14916) | C-peptide levels were associated with risk of CRC (RR: 2.7; 95% CI: 1.2-6.2). |
| Wei et al. [97] | Nested case-control study (n = 32826) | C-peptide levels were associated with risk of colon cancer (RR: 1.76; 95% CI: 0.85-3.63). | |
| Bu et al. [98] | Meta-analysis (n = 491384) | Insulin therapy could increase the risk of CRC. Specifically, insulin use was associated with a statistically significant 115% higher risk of CRC among case-control studies (RR: 2.15; 95% CI: 1.41-3.26), but not among cohort studies (RR: 1.25; 95% CI: 0.95-1.65). | |
| Wang et al. [99] | Meta-analysis (n = 246181) | Insulin use could contribute to the risk of CRC (RR: 1.61; 95% CI: 1.18-1.35). | |
| Yin et al. [100] | Meta-analysis (n = 737562) | Insulin use was significantly associated with risk of CRC (RR: 1.69; 95% CI: 1.25-2.27). | |
| Chen et al. [101] | Meta-analysis (n = 66 324) | Insulin use was associated with an increased risk of CRC (RR: 1.86; 95% CI: 1.58-0-2.19). | |
| Yang et al. [102] | Cohort study (n = 24918) | Insulin therapy significantly increased the risk of CRC (RR: 2.1; 95% CI: 1.2-3.4). | |
| Wu et al. [103] | Meta-analysis (n = 1223812) | Use of insulin analogues (insulin glargine and detemir) was not associated with risk of CRC. | |
| Pradhan et al. [104] | Cohort study (n = 10,734) | Use of long-acting insulin analogs was not associated with an increased risk of colorectal cancer (HR: 0.96; 95% CI: 0.70-1.34). | |
| But et al. [105] | Cohort study (n = 21390) | Use of insulin glargine and insulin detemir was associated with risk of CRC (RR: 1.54; 95% CI: 1.06-2.25). | |
| Metformin | Zhang et al. [107] | Meta-analysis (n = 108161) | Metformin use was associated with lower risk of CRC (RR: 0.63; 95% CI: 0.50-0.79). |
| Singh et al. [108] | Meta-analysis (n = 840787) | Metformin use was associated with an 11% reduction in CRC (RR: 0.89; 95% CI: 0.81-0.99). | |
| Soranna et al. [109] | Meta-analysis (n = 37632) | Metformin use was associated with significantly decreased risk of CRC (RR: 0.64; 95% CI: 0.54-0.76). | |
| Lee et al. [110] | Cohort study (n = 800000) | Metformin could reduce the incidence of CRC (RR: 0.36; 95% CI: 0.13-0.98). | |
| Lee et al. [111] | Cohort study (n = 595) | Metformin use was associated with lower risk of overall mortality (HR: 0.66; 95% CI: 0.476-0.923) and CRC-specific mortality (HR: 0.66; 95% CI: 0.45-0.975) in CRC patients with T2DM. | |
| Baglia et al. [112] | Cohort study (n = 890) | Use of metformin was associated with better overall survival among CRC patients with T2DM (HR: 0.55; 95% CI: 0.34-0.88). | |
| Thiazolidinedione | Singh et al. [108] | Meta-analysis (n = 840787) | TZD use was not associated with CRC risk (OR: 0.96; 95% CI: 0.87-1.05). |
| Colmers et al. [113] | Meta-analysis (n = 2500000) | Use of TZDs was associated with decreased risk of CRC (RR: 0.93; 95% CI: 0.87-1.00). | |
| Chang et al. [114] | Case-control study (n = 606,583) | Rosiglitazone was associated with reduced risk (OR: 0.86; 95% CI: 0.76-0.96), but such protective benefits has not seen in pioglitazone. | |
| Chen et al. [115] | Case-control study (n = 24,496) | TZD use was associated with reduced CRC risk (OR: 0.86; 95% CI: 0.79-0.94). | |
| Liu et al. [116] | Meta-analysis (n = 2470768) | TZD use was associated with reduced CRC risk (RR: 0.91; 95% CI: 0.84-0.99). | |
| Govindarajan et al. [117] | Cohort study (n = 87678) | The TZD-associated risk reduction for CRC did not reach statistical significance. | |
| Sulfonylurea | Singh et al. [108] | Meta-analysis (n = 840787) | Sulfonylurea use was not associated with risk of CRC (OR: 1.11; 95% CI: 0.97-1.26). |
| Soranna et al. [109] | Meta-analysis (n = 37632) | Sulfonylurea use was not associated with risk of CRC. | |
| Shin et al. [118] | Nested case-control study (n = 8436) | Glimepiride use increased the risk for CRC (RR: 1.14; 95% CI: 1.06-1.22), whereas gliclazide decreased the risk for CRC (RR: 0.85; 95% CI: 0.72-1.00). | |
| α-Glucosidase inhibitor | Tseng et al. [119] | Cohort study (n = 1343484) | Acarbose use reduced the risk of CRC in patients with T2DM in a dose-dependent manner (HR: 0.66; 95% CI: 0.59–0.74). |