Incretin‐based drugs and risk of lung cancer among individuals with type 2 diabetes

Abstract

Aim To assess whether dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists are associated with an increased lung cancer risk among individuals with type 2 diabetes. MethodsWe conducted a population-based cohort study using the UK Clinical Practice Research Datalink. We identified 130 340 individuals newly treated with antidiabetes drugs between January 2007 and March 2017, with follow-up until March 2018. We used a time-varying approach to model use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists compared with use of other second-or third-line antidiabetes drugs. We used Cox proportional hazards models to estimate the adjusted hazard ratios, with 95% CIs, of incident lung cancer associated with use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, separately, by cumulative duration of use, and by time since initiation.Results A total of 790 individuals were newly diagnosed with lung cancer (median follow-up 4.6 years, incidence rate 1.5/1000 person-years, 95% CI 1.4-1.6). Compared with use of second-/third-line drugs, use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists was not associated with an increased lung cancer risk (hazard ratio 1.07, 95% CI 0.87-1.32, and hazard ratio 1.02, 95% CI 0.68-1.54, respectively). There was no evidence of duration-response relationships.

Endogenous incretin levels and risk of first incident cancer: a prospective cohort study

“…On the contrary, Ruette et al . did not find any increased risk of lung cancer for users of DPP4i and GLP-1 RA, compared to users of second-/third line drugs 25 . Further, it has been shown that GLP-1 RA can inhibit breast cancer cells growth 13 , and two recent meta-analyses concluded that there was no evidence of GLP-1 RA usage and increased risk of biliary tract cancer 26 , or malignant neoplasia 27 .…”

Sodium‐glucose cotransporter‐2 inhibitors and the risk of lung cancer among patients with type 2 diabetes

“…5 We chose DPP-4 inhibitors as the active comparator group since they are common second-to-third line drugs for the treatment of type 2 diabetes 6,7 and have not been shown to be associated with lung cancer. 8 Cohort entry was the date of the first-ever prescription for an SGLT-2 inhibitor or DPP-4 inhibitor during the study period. At cohort entry, we excluded patients less than 18 years of age, with less than 1 year of medical history, with a history of any cancer other than nonmelanoma skin cancer or with less than 6 months of follow-up.…”

“…These patients have been shown to be largely representative of the general population 5 . We chose DPP‐4 inhibitors as the active comparator group since they are common second‐to‐third line drugs for the treatment of type 2 diabetes 6,7 and have not been shown to be associated with lung cancer 8 . Cohort entry was the date of the first‐ever prescription for an SGLT‐2 inhibitor or DPP‐4 inhibitor during the study period.…”

Metabolic Hormones Modulate Macrophage Inflammatory Responses

“…Similar observations have been made in studies using breast [ 119 ], colon [ 120 ], and ovarian [ 121 ] cancer cell lines, likely due to the inhibition of the PI3K/Akt signaling pathway by exenatide. However, whilst concerns have been raised over the safety of incretin-based treatments for those living with both cancer and diabetes meta-analysis of clinical data has not revealed any association between the development of lung [ 122 ], gastrointestinal [ 123 ] or pancreatic [ 124 ] cancer and the prescriptions of the incretin analogues.…”