Diabetes drugs and the incidence of solid cancers: a survey of the current evidence

Abstract

The evaluation of the relationship between the use of antidiabetic drug and the occurrence of cancer is extremely challenging, both from the clinical and pharmacoepidemiological standpoint. This narrative review described the current evidence supporting a relationship between the use of antidiabetic drugs and the incidence of solid cancers. Areas covered: Data from pharmacoepidemiological studies on cancer incidence were presented for the main antidiabetic drugs and drug classes, including human insulin and insulin analogues, metformin, sulfonylureas, glinides, alpha-glucosidase inhibitors, thiazolidinediones, incretin mimetics, and sodium glucose co-transporter 2 inhibitors. The relationship between the use of antidiabetics and the incidence of solid cancer was described in strata by any cancer and by organ-specific cancer and by drug and by drug classes. Information supporting biological evidence and putative mechanisms were also provided. Expert opinion: The history of exploration of the relationship between antidiabetic drugs and the risk of solid cancers has showed several issues. Unrecognized biases and misinterpretations of study results have had important consequences that delayed the identification of actual risk and benefits of the use of antidiabetic drugs associated with cancer occurrence or progression. The lesson learned from the past should address the future research in this area, since in the majority of cases findings are controversial and confirmatory studies are warranted.

Chemotherapy-Induced Neuropathy and Diabetes: A Scoping Review

“…Chemotherapy-induced neuropathy is a significant source of morbidity in cancer patients, with high incidences (Table 1) and can be a doselimiting side effect for many classes of chemotherapy drugs [5]. Diabetes mellitus is a commonly encountered comorbidity among patients with solid tumors [6][7][8]. Diabetes mellitus and its accompanying metabolic syndrome have been shown to correlate with the development and outcomes of a number of solid tumors [6,7,9].…”

Sulfonylurea and Cancer Risk Among Patients With Type 2 Diabetes: A Population-Based Cohort Study

“…Series of cohort studies suggested that the use of sulfonylurea may increase, decrease, or have no effect on the risk of cancer when compared with other GLDs or non-user of sulfonylurea (28)(29)(30). However, most of these observational studies may have flaws in study design and data analysis methods (7,13). According to the systematic review conducted by Farmer (13), observational studies on comparing cancer risk between users of metformin and sulfonylurea varied in design, and the majority had risks of several kinds of bias due to time-varying confounding and other sources.…”

“…In China and some developed countries, the use of sulfonylureas is second only to or even exceeds the first-line oral GLD metformin ( 5 , 6 ). Although a large number of observational studies about the association between GLDs and cancer incidence have been conducted, evidence of the association between sulfonylurea and cancer risk is still highly controversial ( 4 , 7 ). Besides the diversity of study populations, the majority of these studies suffered from severe methodological limitations, such as immortal time bias and time-varying confounding, which have contributed to the current inconsistent findings ( 4 , 7 ).…”

“…Although a large number of observational studies about the association between GLDs and cancer incidence have been conducted, evidence of the association between sulfonylurea and cancer risk is still highly controversial ( 4 , 7 ). Besides the diversity of study populations, the majority of these studies suffered from severe methodological limitations, such as immortal time bias and time-varying confounding, which have contributed to the current inconsistent findings ( 4 , 7 ). Further, time-varying confounders affected by previous treatment is likely to be an important issue in this context because sulfonylurea use for type 2 diabetes mellitus (T2DM) is influenced by past disease severity, thus can change through time and in turn, sulfonylurea use can affect the status of glycemic control.…”

Synthesis and Comparative Structure–Activity Study of Carbohydrate-Based Phenolic Compounds as α-Glucosidase Inhibitors and Antioxidants

“…Thus, controlling postprandial hyperglycemia is an important target to prevent diabetes as well as diabetic complications. In clinical medicine, α-glucosidase inhibitors such as acarbose, miglitol, and voglibose, belong to the class of antidiabetic drugs used for improving postprandial hyperglycemia [8,9,10,11]. Currently, natural products and their derivatives constitute more than half of the drugs in the clinic [12,13,14,15].…”