<p>Incident cancer risk in dipeptidyl peptidase-4 inhibitor-treated patients with type 2 diabetes mellitus</p>

Abstract

Objective It is known that patients with diabetes are susceptible to cancer development due to long-standing diabetic conditions. This study aimed to investigate new-onset cancer risk associated with dipeptidyl peptidase-4 (DPP-4) inhibitors as compared to metformin, the first-line antidiabetic agent with promising anticancer activity, in patients with type 2 diabetes mellitus (T2DM). Methods A retrospective cohort study of adult T2DM patients was performed at a tertiary care hospital in Korea. Patients who received comparison therapies during 2008–2017 were propensity score (PS)-matched in a 1:1 ratio either to the DPP-4 inhibitors group or to the metformin group in accordance with their primary antidiabetic therapy. Results A total of 1538 patients (769 in each group) were found eligible for study entry. Although the rate of newly diagnosed malignancy, irrespective of specific sites or types, was numerically less frequent in the DPP-4 inhibitors group, the difference in overall cancer risk between groups was not statistically significant (HR=1.00, 95% CI=0.56–1.80, P =0.998). The PS-matched patients were further stratified by relevant patient factors and diabetes severity. No signal of increased risk of malignant complications among DPP-4 inhibitor-receiving diabetic patients was detected in any of the individual strata, nor in the subgroup patients where insulin-exposed patients were excluded from study analyses in consideration of its carcinogenic properties. Patient death or incident pancreatitis events were seldom encountered in both treatment groups; hence such risks were assessed as negligible with the use of either antidiabetic therapy. Conclusion This PS-matched cohort study demonstrated no elevated risk of malignant complications with DPP-4 inhibitor treatment relative to metformin treatment among T2DM patients, irrespective of patient sex, age, comorbid conditions, and diabetes severity status. Similar results were confirmed in the subgroup analyses where a potential confounding effect due to the between-group disparity in insulin co-therapy was eliminated by excluding insulin-exposed patients from risk assessments.

Pancreatitis and pancreatic cancer in patientes treated with Dipeptidyl Peptidase-4 inhibitors: An extensive and updated meta-analysis of randomized controlled trials

“…Regulatory authorities imposed a warning on the risk of pancreatitis for all available DPP-4i. This decision is motivated by a supposed increase in risk of new cases of pancreatitis, suggested by pharmacovigilance reports [1,2] and some metanalyses of randomized trials [21][22][23], but not confirmed by the majority of available observational studies [6][7][8][9][10][11][12]. Notably, both the European Medicines Agency and Food and Drug Administration issued a warning on pancreatitis, without considering a history of pancreatitis as a formal contraindication.…”

“…pancreatitis and pancreatic cancer for both the DPP-4i sitagliptin and the GLP1 receptor agonist exenatide; however, pharmacovigilance reports could overestimate the actual risk, because of over-reporting of unexpected adverse events with newer therapies. However, several observational studies failed to detect any association between incretin-based therapies (i.e., DPP-4i and GLP1 receptor agonists) and pancreatic disease [6][7][8][9][10][11][12], with the exception of only one survey detecting an increased risk [13]. The interpretation of retrospective observational data is problematic, since confounders cannot be entirely accounted for in adjusted models.…”

Clinical Benefits of Oral Anticoagulant Use in Cancer Patients at Increased Risk for Venous Thromboembolism per Khorana Index

“…Anticoagulant users were then classified into two cohorts of either warfarin or NOAC users, in accordance with their primary anticoagulant therapy that lasted for ≥30 consecutive days; NOAC agents include rivaroxaban, apixaban, dabigatran, and edoxaban. Those patients with a history of both treatments for an equivalent length of time, which was defined as the treatment duration not differing by ≥50% of each other’s prescribed days, were excluded from further analysis, 18 leading to two mutually exclusive user groups. Predetermined variables included patient demographics, such as age and gender, cancer sites, Khorana scores, comorbidities, Charlson comorbidity index (CCI) scores, exposure to chemotherapy with high thrombotic risk, including tamoxifen, thalidomide, lenalidomide, cisplatin, fluorouracil, L-asparaginase, bevacizumab, 17 along with concomitant medications with bleeding risk, such as antiplatelets, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and parenteral anticoagulants.…”

CD26/DPP-4: Type 2 Diabetes Drug Target with Potential Influence on Cancer Biology

“…These data suggested that DPP-4 inhibitors induce existing microtumor/precancerous cell visibility rather than inducing de novo carcinogenesis. On the other hand, a propensity-matched cohort study of T2DM patients in Korea represented that DPP-4 inhibitor treatment did not increase the risk of pancreatic and thyroid cancer compared to metformin treatment [ 117 ].…”