Glycemic control and the incidence of neoplasm in patients with type 2 diabetes: a meta-analysis of randomized controlled trials

Purpose: Previous epidemiologic studies indicate an increased risk of cancer and cancer mortality in patients with type 2 diabetes (T2D). Whether the resolution of hyperglycemia will lead to reduced risk of neoplasm in T2D remains uncertain. Therefore, we performed a meta-analysis to assess the association between glycemic control and incidence of neoplasm in T2D patients. Methods: Randomized controlled trials (RCTs) in T2D with significant HbA1c reduction difference between intensive/active and standard/control groups plus follow-up ≥48 weeks were included and analyzed by fixed-effect models, random-effect model, and meta-regression analysis accordingly. Results: Overall, 52 studies were included. Compared with standard/control treatment, intensive/active treatment led to significantly greater HbA1c reduction from baseline (WMD = −0.51%, 95% CI, −0.55 to −0.46%, P < 0.001), but was not associated with a decreased incidence of neoplasm (OR = 0.99, 95% CI, 0.94–1.03, I² = 2%) in T2D. Meta-regression analysis indicated that HbA1c reduction difference between intensive/active treatment and standard/control treatment was not associated with the incidence of neoplasm in T2D patients (β = −0.0011, 95% CI, −0.0058 to 0.0035, P = 0.625). In neoplasm-site subgroup analysis, a decreased incidence of breast neoplasm was observed in T2D patients using dipeptidyl-peptidase-4 inhibitor (OR = 0.56, 95% CI, 0.35–0.89, I² = 0%) and incidence of prostate neoplasm was reduced in T2D patients with glucagon-like peptide-1 receptor agonist treatment (OR = 0.66, 95% CI, 0.47–0.91, I² = 0%). Conclusion: Improved glycemic control in short and medium periods achieved by existing glucose-lowering drugs or strategies may not confer reduced risk of neoplasm in patients with T2D. Studies with longer follow-up duration are needed to better elucidate the long-period effects.