Comparison between sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase 4 inhibitors on the risk of incident cancer in patients with diabetes mellitus: A real-world evidence study

Diabetes Metab Res Rev. 2024 Mar;40(3):e3784. doi: 10.1002/dmrr.3784.

Abstract

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) have been demonstrated to be associated with cancer cell mechanisms. However, whether they increase the risk of cancer remains unclear. Thus, this study aimed to determine the association between SGLT-2i use and the incidence of cancer in patients with diabetes mellitus (DM) in Taiwan.

Materials and methods: This retrospective cohort study was based on the Taiwan National Health Insurance database. The study population comprised patients with DM, and those who first used SGLT-2is during 2016-2018 were assigned to the study group. Greedy propensity score matching was performed to select patients who first used dipeptidyl peptidase 4 inhibitors (DPP-4is), and these patients were assigned to the control group. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for cancer risk in the study and control groups; this model was adjusted for demographic characteristics, DM severity, comorbidities and concomitant medication use.

Results: After controlling for relevant variables, the SGLT-2i cohort (aHR = 0.90, 95% CI = 0.87-0.93) had a significantly lower risk of developing cancer than the DPP-4i cohort, particularly when the SGLT-2i was dapagliflozin (aHR = 0.91, 95% CI = 0.87-0.95) or empagliflozin (aHR = 0.90, 95% CI = 0.86-0.94). Regarding cancer type, the SGLT-2i cohort's risk of cancer was significantly lower than that of the DPP-4i cohort for leukaemia, oesophageal, colorectal, liver, pancreatic, lung, skin and bladder cancer.

Conclusions: SGLT-2i use was associated with a significantly lower risk of cancer than DPP-4i use.

Keywords: cancers; diabetes mellitus; hypoglycemic agents; pharmacoepidemiology; real-world evidence; sodium-glucose cotransporter 2 inhibitors.

Publication types

  • Comparative Study

MeSH terms

  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Glucose
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Neoplasms* / epidemiology
  • Neoplasms* / etiology
  • Retrospective Studies
  • Sodium / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucose
  • Hypoglycemic Agents
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors