Use of Antihyperglycemic Drugs and Risk of Cancer in Patients with Diabetes

Søndergaard, Christian Sümeghy; Esquivel, Paulina Nuñez; Dalamaga, Μaria; Magkos, Faidon

doi:10.1007/s11912-022-01344-7

Cited by 11 publications

(13 citation statements)

References 101 publications

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“…Regarding the association between antihyperglycemic agents and the risk of cancer, recent findings suggest that the risk of cancer associated with the use of antihyperglycemic medications among patients with diabetes depends on the class of drug and type of agent, dosage, and duration of treatment [331]. Among them, the use of insulin and insulin analogs is associated with a significant increase in total cancer risk by almost 50% compared to other antihyperglycemic drugs.…”

Section: Antihyperglycemic Agents and Risk Of Cancermentioning

confidence: 99%

“…Likewise, insulin secretagogues like sulfonylureas have been linked to a ~20% greater risk of cancer, although these associations may be agent-specific and dose-dependent. Alpha-glucosidase inhibitors, e.g., acarbose and thiazolidinediones, have not been consistently associated with cancer [331].…”

Section: Antihyperglycemic Agents and Risk Of Cancermentioning

confidence: 99%

“…Clinical observations support the beneficial effect of metformin on cancer. Metformin is associated with a 20-30% lower risk for all cancers and a greater benefit for cancerrelated mortality [331]. It has two main mechanisms to carry out its anti-diabetic and anti-tumorigenic effect: the AMPK-dependent and independent pathways [312].…”

Section: Metforminmentioning

confidence: 99%

“…Exposure to distinct types of incretin-based therapies, such as glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, has not been found to significantly modify cancer risk [331]. Among GLP-1 agonists, liraglutide exerts cardiovascular protective actions and can preserve endothelial barrier integrity by reversing the oxLDL-induced downregulation of tight junction proteins and attenuating oxLDL-induced endothelial permeability [333].…”

Section: Incretin-based Therapiesmentioning

confidence: 99%

“…The potential for protection against cancer formation and progression from in vitro and animal studies was not confirmed by randomized and observational studies or their meta-analyses [339]. Inhibitors of sodium glucose cotransporter-2 may raise the risk of bladder cancer and reduce the risk of gastrointestinal cancer [331,340]. Statins inhibit β-Hydroxy-β-methylglutaryl-CoA (HMG-CoA) reductase, which catalyzes the rate-limiting step in hepatic cholesterol biosynthesis and inhibits the mevalonate pathway [341].…”

Section: Inhibitors Of Sodium Glucose Cotransporter-2mentioning

confidence: 99%

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Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management

Katsi

Papakonstantinou

Tsioufis

2023

IJMS

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The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest in basic science. It has been recognized, from the most recent research, that metabolic syndrome-related conditions, ranging from atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism and lipid signaling that are also linked to the same framework of multiple potential mechanisms for inducing cancer. Otherwise, dyslipidemia and endothelial cell dysfunction in atherosclerosis may present common or even interdependent changes, similar to oncogenic molecules elevated in many forms of cancer. However, whether endothelial cell dysfunction in atherosclerotic disease provides signals that promote the pre-clinical onset and proliferation of malignant cells is an issue that requires further understanding, even though more questions are presented with every answer. Here, we highlight the molecular mechanisms that point to a causal link between lipid metabolism and glucose homeostasis in metabolic syndrome-related atherosclerotic disease with the development of cancer. The knowledge of these breakthrough mechanisms may pave the way for the application of new therapeutic targets and for implementing interventions in clinical practice.

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Section: Antihyperglycemic Agents and Risk Of Cancermentioning

confidence: 99%

Section: Antihyperglycemic Agents and Risk Of Cancermentioning

confidence: 99%

Section: Metforminmentioning

confidence: 99%

Section: Incretin-based Therapiesmentioning

confidence: 99%

Section: Inhibitors Of Sodium Glucose Cotransporter-2mentioning

confidence: 99%

See 3 more Smart Citations

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management

Katsi

Papakonstantinou

Tsioufis

2023

IJMS

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Diabetes and the risk of bladder cancer subtypes in men and women: results from the Netherlands Cohort Study

van den Brandt

2024

Eur J Epidemiol

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Meta-analyses have shown modest positive associations between diabetes mellitus (DM) and bladder cancer risk, but results are heterogeneous. This might be due to lack of distinction between bladder cancer subtypes, between sexes, and possibly between Type 2 and Type 1 DM (T2DM and T1DM). The relationship of T2DM (and secondarily T1DM) characteristics with risk of bladder cancer subtypes (invasive versus noninvasive) was investigated in the Netherlands Cohort Study. In 1986, 120,852 men and women aged 55–69 years provided information on DM and lifestyle data. After 20.3 years of follow-up, multivariable case-cohort analyses were based on 1020 invasive and 1088 noninvasive bladder cancer cases, and 4267 subcohort members with complete data on DM and confounders. While T2DM was not associated with noninvasive bladder cancer, it was statistically significantly associated with invasive bladder cancer risk: the multivariable-adjusted was HR = 1.57 (95% CI 1.04–2.37), comparing participants with T2DM versus without DM. The association was only significant in women, and women showed a stronger association [HR = 2.19 (95% CI 1.10–4.34)] between T2DM and invasive bladder cancer than men [HR = 1.42 (95% CI 0.88–2.30)]; interaction by sex was nonsignificant. Associations were stronger positive in those whose age at diagnosis of T2DM was 55+ years, and in those diagnosed with T2DM less than five years before baseline. T2DM participants using antidiabetic medication had higher invasive bladder cancer risk than those without DM. Exploratory age-sex-adjusted analyses suggested a positive association between T1DM and invasive bladder cancer, but this was based on few cases. These findings suggest that T2DM and possibly T1DM are positively associated with invasive bladder cancer risk.

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Obesity and Leukemia: Biological Mechanisms, Perspectives, and Challenges

Tsilingiris,

Vallianou,

Spyrou

et al. 2023

Curr Obes Rep

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Purpose of Review To examine the epidemiological data on obesity and leukemia; evaluate the effect of obesity on leukemia outcomes in childhood acute lymphoblastic leukemia (ALL) survivors; assess the potential mechanisms through which obesity may increase the risk of leukemia; and provide the effects of obesity management on leukemia. Preventive (diet, physical exercise, obesity pharmacotherapy, bariatric surgery) measures, repurposing drugs, candidate therapeutic agents targeting oncogenic pathways of obesity and insulin resistance in leukemia as well as challenges of the COVID-19 pandemic are also discussed. Recent Findings Obesity has been implicated in the development of 13 cancers, such as breast, endometrial, colon, renal, esophageal cancers, and multiple myeloma. Leukemia is estimated to account for approximately 2.5% and 3.1% of all new cancer incidence and mortality, respectively, while it represents the most frequent cancer in children younger than 5 years. Current evidence indicates that obesity may have an impact on the risk of leukemia. Increased birthweight may be associated with the development of childhood leukemia. Obesity is also associated with worse outcomes and increased mortality in leukemic patients. However, there are several limitations and challenges in meta-analyses and epidemiological studies. In addition, weight gain may occur in a substantial number of childhood ALL survivors while the majority of studies have documented an increased risk of relapse and mortality among patients with childhood ALL and obesity. The main pathophysiological pathways linking obesity to leukemia include bone marrow adipose tissue; hormones such as insulin and the insulin-like growth factor system as well as sex hormones; pro-inflammatory cytokines, such as IL-6 and TNF-α; adipocytokines, such as adiponectin, leptin, resistin, and visfatin; dyslipidemia and lipid signaling; chronic low-grade inflammation and oxidative stress; and other emerging mechanisms. Summary Obesity represents a risk factor for leukemia, being among the only known risk factors that could be prevented or modified through weight loss, healthy diet, and physical exercise. Pharmacological interventions, repurposing drugs used for cardiometabolic comorbidities, and bariatric surgery may be recommended for leukemia and obesity-related cancer prevention.

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Use of Antihyperglycemic Drugs and Risk of Cancer in Patients with Diabetes

Cited by 11 publications

References 101 publications

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management

Atherosclerosis, Diabetes Mellitus, and Cancer: Common Epidemiology, Shared Mechanisms, and Future Management

Diabetes and the risk of bladder cancer subtypes in men and women: results from the Netherlands Cohort Study

Obesity and Leukemia: Biological Mechanisms, Perspectives, and Challenges

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