Risk Of Cancer In Type Research Articles

S699 GLP-1 Receptor Agonists Are Associated With Decreased Esophageal Cancer Risk in Type 2 Diabetes Patients Compared to Other Anti-Diabetic Therapy

S699 GLP-1 Receptor Agonists Are Associated With Decreased Esophageal Cancer Risk in Type 2 Diabetes Patients Compared to Other Anti-Diabetic Therapy

Gene expression profiling and protein–protein network analysis revealed prognostic hub biomarkers linking cancer risk in type 2 diabetic patients

Type 2 diabetes mellitus (T2DM) and cancer are highly prevalent diseases imposing major health burden globally. Several epidemiological studies indicate increased susceptibility to cancer in T2DM patients. However, genetic factors linking T2DM with cancer have been poorly studied. In this study, we followed computational approaches using the raw gene expression data of peripheral blood mononuclear cells of T2DM and cancer patients available in the gene expression omnibus (GEO) database. Our analysis identified shared differentially expressed genes (DEGs) in T2DM and three common cancer types, namely, pancreatic cancer (PC), liver cancer (LC), and breast cancer (BC). The functional and pathway enrichment analysis of identified common DEGs highlighted the involvement of critical biological pathways, including cell cycle events, immune system processes, cell morphogenesis, gene expression, and metabolism. We retrieved the protein–protein interaction network for the top DEGs to deduce molecular-level interactions. The network analysis found 7, 6, and 5 common hub genes in T2DM vs. PC, T2DM vs. LC, and T2DM vs. BC comparisons, respectively. Overall, our analysis identified important genetic markers potentially able to predict the chances of PC, LC, and BC onset in T2DM patients.

Lower Incidence of Leukemia in Sodium Glucose Cotransporter-2 Inhibitor-Treated Patients with Type 2 Diabetes Mellitus: Result from Large Real-World Cohorts

Objective: Leukemia is the among the top ten most common cancer in the United States of America, with incidence of 14.0 per 100,000 people. While the incidence of non-Hodgkin lymphoma has significantly decreased, the incidence of leukemia has been stable during 2014-2018 [1]. In the meantime, sodium-glucose cotransporter-2 inhibitors (SGLT-2i), a comparatively new class of anti-diabetic medication, has gained significant popularity among clinician due to its cardioprotective and renoprotective properties. Several observational studies and meta-analyses explored the relationship between SGLT-2i and solid tumor, including bladder cancer and breast cancer [2, 3]. Nevertheless, contemporary data for SGLT-2i and leukemia are limited. This large cohort study was aimed to investigate the association between SGLT-2i and the risk of leukemia. Methods: This was a retrospective cohort study including patients with T2DM from 92 hospitals across the United States between 2015 and 2023. Inclusion criteria were patients with T2DM aged 18 years or older who newly initiated treatment with SGLT-2i or DPP-4i. Patients with a history of type 1 diabetes or malignancies were excluded. Propensity score matching was applied to each group to account for confounding factors, including demographic characteristics, comorbidities, laboratory data, and medication history. The primary outcome of interest was the occurrence of incident leukemia, including lymphoid leukemia, myeloid leukemia and monocytic leukemia. Kaplan-Meier analysis and log-rank tests were used to compare the outcomes across the cohorts, while hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using the Cox proportional hazard regression model. Results: A total of 718,276 SGLT-2i initiators were matched to 1,159,112 DPP4i initiators diagnosed with T2DM. Among these, 3,429 incidents of leukemia were identified, with 1,148 occurring in the SGLT2i groups and 2,281 in the DPP-4i group after matching.The baseline characteristics, including ethnicity, comorbidities and medication history, were well-balanced between the two cohorts. SGLT-2i initiators demonstrated a significantly reduced risk of new-onset leukemia compared to those using DPP-4i, including myeloid leukemia (HR, 0.676; 95% CI, 0.589 to 0.776, p < 0.001) and lymphoid leukemia (HR, 0.846; 95% CI, 0.753-0.950, p = 0.005). There was no significant difference in the occurrence of monocytic leukemia (aHR 0.836; 95% CI, 0.556 to 1.257, p = 0.388). Conclusion: This population-based propensity-score matched cohort study showed that SGLT-2i is associated with lower in the risk of developing leukemia when compared to those treated with DPP-4i. These findings highlight the potential therapeutic value of SGLT-2i in the prevention of hematological malignancies in patients with T2DM. Further clinical trials are necessary to explore and validate the potential applications. Reference 1. Cronin, K.A., et al., Annual report to the nation on the status of cancer, part 1: National cancer statistics. Cancer, 2022. 128(24): p. 4251-4284. 2. Garcia, M., et al., SGLT2 Inhibitors and Bladder Cancer: Analysis of Cases Reported in the European Pharmacovigilance Database. J Clin Pharmacol, 2021. 61(2): p. 187-192. 3. Tang, H., et al., SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials. Diabetologia, 2017. 60(10): p. 1862-1872.

Increased Breast and Colorectal Cancer Risk in Type 2 Diabetes: Awareness Among Adults With and Without Diabetes and Information Provision on Diabetes Websites.

People with type 2 diabetes mellitus (T2DM) have a higher risk of developing breast and bowel cancers but are less likely to participate in cancer screening. Two interlinked studies examined public awareness of the fact that T2DM increases breast and bowel cancer risk, and provision of this information on diabetes websites. Study-1: phase-1 surveyed awareness of T2DM-increased cancer risk in a nationally-representative British sample aged 50-74 (N = 1,458) and compared respondents with and without T2DM (n = 125 vs. n = 1,305); phase-2 surveyed an additional exclusively T2DM sample (N = 319). Study-2: High-ranking diabetes websites (N = 25) were reviewed to determine the rate of inclusion of cancer risk and cancer screening information in evident sections about diabetes-related health conditions. A low proportion of respondents were aware that T2DM increases risk of breast (13.7%) and bowel (27.6%) cancers, compared to much higher awareness of other diabetes-related conditions such as sight loss (82.2%) and foot problems (81.8%). Respondents with T2DM were significantly more likely than those without T2DM to be aware of all the surveyed diabetes-related health conditions (e.g., sight loss, OR: 3.14, 95%CI: 1.61-6.15; foot problems, OR: 2.58, 95%CI: 1.38-4.81), except breast (OR: 0.82, 95%CI: 0.46-1.45) and bowel (OR: 0.95, 95%CI: 0.63-1.45) cancer, for which awareness was equally low among people with and without T2DM. Few diabetes websites with a section on diabetes-related health conditions included cancer in this section (n = 4/19), and fewer still included cancer screening among any noted cancer-protective behaviors (n = 2/4). There is low public awareness that T2DM increases the risk of developing breast and bowel cancers, even among people with T2DM, which may be partly due to limited information provision regarding T2DM-increased cancer risk from diabetes care providers and organizations.

Diabetes and cancer: Optimising glycaemic control.

Diabetes and cancer are both common and increasingly prevalent conditions, but emerging epidemiological evidence confirms that the risk of developing a number of common cancers is increased in those with type 2 diabetes. The risk of cancer in type 1 diabetes is less clearly defined, and therefore this review focuses on type 2 diabetes. Emerging evidence also supports an influence of diabetes on outcomes of cancer treatment. However, this relationship is bi-directional, with cancer and its treatment impacting on glucose control, whereas there is also emerging evidence indicating that diabetes care can deteriorate after a cancer diagnosis. Despite these clear links, there is a lack of evidence to guide clinicians in how to manage patients with diabetes during their cancer treatment. Although recent UK guidelines have started to address this, with the development of guidance for the management of hyperglycaemia in cancer, there is a clear need for wider guidance on the management of multi-morbidity during cancer, including diabetes and obesity, to incorporate nutritional management. We have therefore undertaken a narrative review of the evidence of links between type 2 diabetes and cancer incidence and outcomes, and discuss the challenges to diabetes care during cancer treatment.

Metformin and Cancer, an Ambiguanidous Relationship.

The deregulation of energetic and cellular metabolism is a signature of cancer cells. Thus, drugs targeting cancer cell metabolism may have promising therapeutic potential. Previous reports demonstrate that the widely used normoglycemic agent, metformin, can decrease the risk of cancer in type 2 diabetics and inhibit cell growth in various cancers, including pancreatic, colon, prostate, ovarian, and breast cancer. While metformin is a known adenosine monophosphate-activated protein kinase (AMPK) agonist and an inhibitor of the electron transport chain complex I, its mechanism of action in cancer cells as well as its effect on cancer metabolism is not clearly established. In this review, we will give an update on the role of metformin as an antitumoral agent and detail relevant evidence on the potential use and mechanisms of action of metformin in cancer. Analyzing antitumoral, signaling, and metabolic impacts of metformin on cancer cells may provide promising new therapeutic strategies in oncology.

The Risk of Bladder Cancer in Type 2 Diabetes Mellitus with Combination Therapy of SGLT-2 Inhibitors and Pioglitazone.

Background: Either sodium-glucose cotransporter-2 (SGLT-2) inhibitors or pioglitazone (Pio) has doubtful issues of bladder cancer, especially for the combination therapy with these two drugs. Our study aimed to investigate the risk of bladder cancer under combination therapy of SGLT-2 inhibitors and Pio. Materials and Methods: We included 97,024 patients with type 2 diabetes mellitus (T2DM) in the Chang Gung Research Database in Taiwan from 1 January 2016 to 31 December 2019. The primary outcome was newly diagnosed bladder cancer after combination therapy with SGLT-2 inhibitors and Pio. Group 1 received both study drugs, group 2 received SGLT-2 inhibitors, group 3 received Pio, and group 4 received non-study drugs (the reference group). The secondary outcome in each group was all-cause mortality. Results: In group 1, no newly diagnosed bladder cancer was detected after a mean 2.8-year follow-up and all-cause mortality decreased significantly (adjusted hazard ratio (AHR), 0.70; 95% confidence interval (CI), 0.54–0.92) in comparison to the reference group (group 4). In group 2 and group 3, no trend of increased bladder cancer was observed (group 2: AHR 0.49, 95% CI 0.05–4.94; group 3: AHR 0.48, 95% CI 0.15–1.58) and it still reduced all-cause mortality (group 2: AHR 0.83, 95% CI 0.70–0.99; group 3: AHR 0.90, 95% CI 0.83–0.99). Conclusions: In T2DM patients without previous or active bladder cancer, the combination therapy of SGLT-2 inhibitors and Pio was not associated with newly diagnosed bladder cancer and had lower all-cause mortality.

1106-P: Glycemic Burden and Obesity Independently Increased Risk of Liver Cancer in Type 2 Diabetes: Hong Kong Diabetes Register (1995-2019)

The incidence of liver cancer and related mortality is increasing globally. Liver is a major site for glucose metabolism. People with type 2 diabetes (T2D) had increased risk of liver cancer. However, the association of glycemic burden (GB) with liver cancer in T2D remains unclear. We calculated GB using area under the curve above 5.7% of HbA1c (AUC_A1c) in patients with T2D enrolled in the prospective Hong Kong Diabetes Register established since 1995. Structured baseline data were linked to laboratory and hospitalization records in a territory-wide electronic medical record system with data censored in 2019. We performed Cox regression analysis to investigate the association of GB with incident liver cancer defined as first hospitalization with ICD9 code (155). We included 18,173 patients (50.93% male, age: 58.43±12.48 years, HbA1c: 7.58±1.66%, BMI: 25.51±4.06 kg/m2, disease duration: 20.68 ±7.63 years), who had ≥ 10 years of disease duration, > 3 years of observation, and ≥ 5 HbA1c measurements (21.98±12.33). During a median (IQR) follow up period of 10.62 (8.09, 15.88) years (218,381patient-years), 160 patients developed liver cancer with an incidence of 7.33 per 10,000 patient-years. We excluded 3 years of HbA1c values prior to incident liver cancer to avoid reverse causality. After adjusting for confounders, every 1 unit increase in AUC_A1c increased the hazard ratio (HR) of liver cancer by 1.22 (95% CI: 1.01-1.47), while AUC_A1c top quantile group had a HR of 1.78 (1.01-3.13) versus the lowest quantile group. In subgroup analysis, obese patients (BMI>25 kg/m2) had a HR of 1.34 (1.05-1.70) for liver cancer versus non-obese subjects. Amongst patients who developed liver cancer (n=1420) within 3 years of enrolment, one unit increase of AUC_A1c was associated with a HR of 1.49 (1.07-2.07) for liver cancer. GB and obesity independently increased the risk of liver cancer in T2D, emphasizing the importance of metabolic control for cancer risk reduction. Disclosure D. Mao: None. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. E. S. H. Lau: None. A. Yang: None. H. Wu: None. M. Shi: None. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. A. Luk: None.

Diabetes, Antidiabetic Medications and Cancer Risk in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

In the last decade, cancer became the leading cause of death in the population under 65 in the European Union. Diabetes is also considered as a factor increasing risk of cancer incidence and mortality. Type 2 diabetes is frequently associated with being overweight and obese, which also plays a role in malignancy. Among biological mechanisms linking diabetes and obesity with cancer hyperglycemia, hyperinsulinemia, insulin resistance, increased levels of growth factors, steroid and peptide hormones, oxidative stress and increased activity of pro-inflammatory cytokines are listed. Antidiabetic medications can modulate cancer risk through directly impacting metabolism of cancer cells as well as indirectly through impact on risk factors of malignancy. Some of them are considered beneficial (metformin and thiazolidinedions—with the exception of bladder cancer); on the other hand, excess of exogenous insulin may be potentially harmful, while other medications seem to have neutral impact on cancer risk. Inhibitors of the sodium-glucose cotransporter-2 (SGLT-2) are increasingly used in the treatment of type 2 diabetes. However, their association with cancer risk is unclear. The aim of this review was to analyze the anticancer potential of this class of drugs, as well as risks of site-specific malignancies associated with their use.

Abstract PO-088: Low levels of PSA in diabetic Nigerians: A call for a separate reference range for prostate cancer screening among type-2 diabetics?

Abstract INTRODUCTION Diabetic patients are at higher risk of developing malignancies. Studies have however suggested a contrasting data, indicating lower risk of prostate cancer in type 2 diabetics. Studies in some parts of the world showed lower PSA levels in diabetic patients, but yet to be verified in African living in Africa. AIM The aim was to determine the levels of PSA in Diabetic and Non-diabetic men in Maiduguri-Nigeria and to ascertain similar lower values in African living in Africa. MATERIALS AND METHODS This was a hospital based case-control study that included a total of 132 participants whose ages were from 40 years and above and voluntarily consented to be part of this study. Ethical clearance was obtained from Ethics and Research Committee of the University of Maiduguri Teaching Hospital, structured questionnaire was self-administered. One hundred and four (104) were confirmed type 2 DM male attending Metabolic Clinic University of Maiduguri Teaching Hospital and twenty eight (28) non-diabetic men, who had no history of hypertension, not using antihypertensives or steroid drugs, no history of cardiovascular diseases, not using anti-lipid drugs; not having cancer; non-smokers and non-alcoholic consented and served as control. Data on family history of DM, duration of the disease, hypertension and social lifestyle recorded for diabetic patients. Weight, height and BMI were calculated, Blood pressure, fasting glucose and serum for PSA were determined. RESULTS The mean ages of diabetic and non- diabetic men were 53.3 ± 11.8 and 53.9 ± 6.1 years, respectively. The mean total serum PSA was significantly lower in diabetic compared to non-diabetic (0.72 ± 0.09 ng/ml vs. 2.50 ± 0.44 ng/ml, respectively, p = 0.000). The mean fasting glucose was significantly higher among diabetic compared to non-diabetic p = 0.006). Diabetics were grouped into 5 according to their age (40 -49, 50-59, 60-69,70-79, ≥ 80). The age 70-79 years has the highest mean PSA level than all other groups (1.19 ± 0.45ng/ml), while age group ≥ 80 years has the least PSA value of (0.15 ± 0.05ng/ml). The mean fasting glucose is lowest in age group of ≥ 80years and highest in age groups of 50-59 and 40-49years (7.78 ± 0.68 and 7.56 ± 0.63mmol/L) respectively. The treatment modality was grouped into five; insulin 5(4.8%), oral 73(70.2%), oral and insulin 8(7.7%) and diet 18 (13.6%). Oral and insulin treatment has higher level of PSA (1.29 ±1.03 ng/ml) compared to all the other groups. The PSA levels were grouped based on the duration of diagnosis of DM (0-5, 6-10, 11-15, 16-20 and ≥ 21years) and 11-15 years duration have high levels of PSA than the other group. There was significant Pearson’s Correlation between PSA and age, systolic and diastolic (p=0.000, p=0.002 and p=0.006) respectively. CONCLUSION serum PSA level is significantly lower in type 2 diabetics than in non-diabetics in this study. This study and other findings recommend establishment of separate reference interval for Type 2 diabetic men for appropriate evaluation of their prostatic diseases using the PSA Citation Format: Rebecca Mtaku Gali, Dahiru Saleh Mshelia, Jessy Thomas Medugu, Musa Dungus, Hassan Dogo, Haruna Asura Nggada, Bata Mtaku Gali, Mwajim Bukar, Ahmad Gadam Ibrahim, Galadima Gadzama, Abubakar Farate. Low levels of PSA in diabetic Nigerians: A call for a separate reference range for prostate cancer screening among type-2 diabetics? [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-088.

The effect of metformin on esophageal cancer risk in patients with type 2 diabetes mellitus: a systematic review and meta‑analysis.

Recently, numerous studies have yielded inconsistent results regarding the effect of metformin on esophageal cancer risk in type 2 diabetes mellitus patients. The purpose of this study is to systematically assess this effect using meta-analysis. We searched clinical studies on metformin and esophageal cancer risk in PubMed, Embase, and the Cochrane Library. After literature screening, a series of meta-analyses were conducted using RevMan 5.3 software. The pooled hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the effect size. Five eligible studies (four cohort studies and one case-control study) were included for our meta-analysis using a random-effect model. The analysis showed that metformin could not reduce esophageal cancer risk in type 2 diabetes mellitus patients (HR 0.88, 95% CI 0.60-1.28, P > 0.05). Subgroup analyses by geographic location showed that metformin significantly reduced esophageal cancer risk in Asian patients with type 2 diabetes mellitus (HR 0.59, 95% CI 0.39-0.91, P = 0.02), without heterogeneity between studies (P = 0.80 and I2 = 0%). Overall, our systematic review and meta-analysis demonstrate that metformin does not reduce esophageal cancer risk in type 2 diabetes mellitus patients. However, a significant reduction in esophageal cancer risk in Asian populations remains to be clarified.

A Cohort Study of Antihyperglycemic Medication Exposure and Gastric Cancer Risk.

We assessed gastric cancer risk in type 2 diabetes mellitus patients. Gastric cancer patients with diabetes between 2001–2012 were identified. Four groups were analysed: combination therapy with metformin users; insulin and other medication users; metformin and insulin users; and sulfonylurea users. Standardised incidence ratios (SIRs) for gastric cancers as a ratio of the observed number of cancer cases in people with diabetes to the expected number of cancer cases in the underlying general population were calculated. A total of 99,992 patients with diabetes were analysed and 337 gastric cancer cases in patients with diabetes were observed when compared to the expected number of 400.54 gastric cancer cases, according to the cancer rates of the general population (SIR 0.84, 95% confidence interval (CI): 0.76–0.94). Lower risk of gastric cancer was found both in male and female patients with diabetes, however, risk among females was insignificantly lower. Higher gastric cancer risk was found in the group of diabetic patients treated with sulfonylureas (SIR 1.31, 95% CI: 1.04–1.65) and significantly lower risk than expected from the general population was found in the group of metformin users (SIR 0.75, 95% CI: 0.66–0.86). Type 2 diabetes mellitus was not associated with increased risk of gastric cancer. Metformin might decrease the risk of gastric cancer in patients with diabetes, while sulfonylureas may increase gastric cancer risk.

GLP-1 receptor agonists and risk of cancer in type 2 diabetes: an updated meta-analysis of randomized controlled trials.

Some preliminary studies reported a link between GLP-1 receptor agonists (GLP-1RAs) and thyroid/pancreatic neoplasms, while its human relevance remained undetermined. The present meta-analysis was performed to collect information on cancers associated with GLP-1RAs in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and ClinicalTrials.gov were extensively searched to identify randomized controlled trials that reported cancer events in T2DM patients treated with GLP-1RAs for at least 52 weeks, up to March 18, 2019. Odds ratio (OR) with 95% Confidence Interval (CI) was calculated for overall cancer (primary outcome), thyroid and pancreatic cancer. A total of 37 eligible trials were identified. The OR for overall cancer associated with GLP-1RAs was 1.03 (95% CI 0.95-1.12; p = 0.41) compared with comparators. Subgroup analyses showed that treatment with albiglutide was associated with a lower risk of overall cancer (OR 0.76 [95% CI 0.60-0.97]; p = 0.03), and no elevated risk of overall cancer was identified for other GLP-1RAs. No significant differences in the risks of thyroid nor pancreatic cancer were disclosed between GLP-1RAs and comparators. This meta-analysis did not suggest any increased risk of cancers associated with GLP-1RAs use in T2DM. The reduction in the risk of overall cancer associated with albiglutide needs to be examined further.

Correlation between renin-angiotensin system (RAS) related genes, type 2 diabetes, and cancer: Insights from metanalysis of transcriptomics data

Although studies have provided significant evidence about the role of RAS in mediating cancer risk in type 2 diabetes mellitus (DM), conclusions about the central molecular mechanisms underlying this disease remain to be reached, because this type of information requires an integrative multi-omics approach. In the current study, meta-analysis was performed on type 2 diabetes and breast, bladder, liver, pancreas, colon and rectum cancer-associated transcriptome data, and reporter biomolecules were identified at RNA, protein, and metabolite levels using the integration of gene expression profiles with genome-scale biomolecular networks in diabetes samples. This approach revealed that RAS biomarkers could be associated with cancer initiation and progression, which include metabolites (particularly, aminoacyl-tRNA biosynthesis and ABC transporters) as novel biomarker candidates and potential therapeutic targets. We detected downregulation and upregulation of differentially expressed genes (DEGs) in blood, pancreatic islets, liver and skeletal muscle from normal and diabetic patients. DEGs were combined with 211 renin-angiotensin-system related genes. Upregulated genes were enriched using Pathway analysis of cancer in pancreatic islets, blood and skeletal muscle samples. It seems that the changes in mRNA are contributing to the phenotypic changes in carcinogenesis, or that they are as a result of the phenotypic changes associated with the malignant transformation. Our analyses showed that Ctsg and Ednrb are downregulated in cancer samples. However, by immunohistochemistry experiments we observed that EDNRB protein showed increased expression in tumor samples. It is true that alterations in mRNA expression do not always reflect alterations in protein expression, since post-translational changes can occur in proteins. In this study, we report valuable data for further experimental and clinical analysis, because the proposed biomolecules have significant potential as systems biomarkers for screening or for therapeutic purposes in type 2 diabetes and cancer-associated pathways.

Abstract 2236: Metformin and pancreatic cancer risk in Taiwanese patients with type 2 diabetes

Abstract Background: Whether metformin may reduce pancreatic cancer risk is controversial and has rarely been studied in Asian populations. This study evaluated pancreatic cancer risk in type 2 diabetes patients with and without metformin treatment. Methods: An original cohort of 16232 never users and 153408 ever users of metformin who were newly diagnosed of type 2 diabetes between 1999 and 2005 were enrolled from Taiwan's National Health Insurance. A propensity score matched cohort of 16232 ever users and 16232 never users were derived from this original cohort. The patients were followed up until December 31, 2011 and analyses were conducted in both the original cohort and the matched cohort. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results: In the original cohort, the incidence rate of pancreatic cancer in never users and ever users were 43.59 and 28.85 per 100000 person-years, respectively, with an overall hazard ratio of 0.658 (95% confidence interval: 0.438-0.988, P=0.0436). While compared to never users, the hazard ratio (95% confidence interval) for cumulative duration of metformin use in the first (<22.10 months), second (22.10-46.70 months) and third tertile (>46.70 months) was 1.445 (0.950-2.196), 0.595 (0.384-0.922) and 0.157 (0.094-0.264), respectively. Results in the matched cohort were very similar, with an overall hazard ratio of 0.492 (0.252-0.961) and the hazard ratio in the respective tertile of cumulative duration was 0.900 (0.368-2.198), 0.648 (0.266-1.581) and 0.094 (0.013-0.692). Conclusions: Metformin significantly reduces pancreatic cancer risk in a dose-response pattern. Citation Format: Chin-Hsiao Tseng. Metformin and pancreatic cancer risk in Taiwanese patients with type 2 diabetes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2236.

PCN42 - Use of Anti-Diabetic Medication is Not Associated with Cancer Risk in Chinese Patients with Type 2 Diabetes

Based on some meta-analyses of observational studies and several RCT, it is not conclusive whether metformin use reduces cancer risk in type 2 diabetes. This study aimd to investigate whether use of anti-diabetic medication including metformin, sulfonylureas, thiazolidinediones, α-glucosidase inhibitors and insulin is associated with the overall and site-specific cancer risk, controlling for potential bias. Data were obtained from Tianjin Urban Employee Basic Medical Insurance database (2003-2014). Adult patients who were newly diagnosed with type 2 diabetes in 2009, and only used 1 class of anti-diabetic medication during the 1st year follow-up were included and grouped accordingly. Newly-diagnosed patients who had no prescription of antidiabetic medication during the whole follow-up period were identified as the untreated group. Overall and 5 site-specific (stomach, colorectum, liver, lung, breast) cancer incidence rates were calculated for all 6 groups during follow-up. Multivariate Cox proportional hazards models adjusting for baseline characteristics were further conducted. A total of 3901 diabetic patients were included (648 for untreated, 630 for metformin, 1053 for sulfonylureas, 159 for thiazolidinediones, 613 for α-glucosidase inhibitors, and 798 for insulin). The average ages were between 58.2 to 60.8 years across 6 groups. During the 5-year follow-up period, 161 patients were newly diagnosed with cancer, without significant differences of cancer incidence rates presented across 6 groups. Compared with the untreated group, the hazard ratios of overall cancer risk were 0.68 [95%CI: 0.38-1.23] for metformin, 0.87 [0.54-1.40] for sulfonylureas, 0.59 [0.21-1.70] for thiazolidinediones, 1.09 [0.65-1.83] for α-glucosidase inhibitors and 1.09 [0.66-1.81] for insulin group. Similar to the findings regard to overall cancer risk, no significant differences regard to site-specific cancer risk were detected across 6 groups. No association was found between antidiabetic medication use and cancer risk among patients with newly-diagnosed type 2 diabetes in China.

SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.

The association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes. We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs. In total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]). Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.

Antidiabetic medications use and cancer risk in type 2 diabetes

Introduction. The risk of several types of cancer is increased in type 2 diabetes mellitus (T2DM). Impact of antidiabetic medications on this risk is still a matter of controversies. The aim of our observational study was to evaluate the risk of cancer occurrence associated with the most frequently used antidiabetic agents. Material and methods. 213 patients (118 women) with T2DM who developed cancer while treated for diabetes and 213 subjects with T2DM without cancer, matched by age and gender in a 1:1 case-control manner were included. Date of cancer diagnosis was considered as index time, and for each comparator data from the same calendar time were used. Results. Both in the univariate and in multiple logistic regression analysis metformin use was associated with reduced cancer risk, while elevated risk associated with insulin use was significant only in univariate but not in multiple logistic regression analysis. Insulin and sulfonylurea derivatives in monotherapy were associated with significantly higher cancer risk compared to metformin monotherapy, while in combination with metformin this risk was attenuated to non-significant level. Conclusion. Our study suggests protective effect of metformin and potentially negative impact of insulin and sulfonylurea derivatives on cancer risk. These findings should be interpreted with caution, due to relatively small study group. Nevertheless, to minimize cancer risk associated with antidiabetic medications’ use, metformin should be continued as long as medically acceptable and it should be combined with insulin or SU to neutralize risk associated with using either of the latter drugs in monotherapy.

Sitagliptin and oral cancer risk in type 2 diabetes patients.

The reimbursement database of the Taiwan’s National Health Insurance was used to evaluate oral cancer risk after sitagliptin use. Patients newly diagnosed of type 2 diabetes during 1999–2008 were recruited. A 1:1 propensity score matched-pair sample of 39195 ever users and 39195 never users were followed up until December 31, 2011. Cox regression incorporated with the inverse probability of treatment weighting using propensity score was used to estimate hazard ratios. Results showed that the overall hazard ratio was not statistically significant (0.956, 95% confidence interval: 0.652–1.401). However, in tertile analyses, the hazard ratio for the first (< 7.47 months), second (7.47–15.63 months) and third (> 15.63 months) tertile of cumulative duration was 1.563 (0.963–2.537), 1.236 (0.738–2.071) and 0.345 (0.164–0.725), respectively; and was 1.575 (0.963–2.575), 1.224 (0.738–2.033) and 0.347 (0.165–0.731), respectively, for the first (< 19,600 mg), second (19,600–42,200 mg) and third (> 42,200 mg) tertile of cumulative dose. Sensitivity analyses after excluding patients who developed any other cancer during follow-up did not change the results substantially. Additionally, the risk of oral diseases that may predispose to oral cancer (i.e., “gingival and periodontal diseases" and/or "oral mucosal lesions") paralleled the risk pattern of oral cancer, suggesting a possible explanation for the risk change of oral cancer related to sitagliptin. In conclusion, sitagliptin may reduce oral cancer risk when the cumulative duration is > 15.63 months or the cumulative dose is > 42,200 mg.

Metformin therapy and risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

Recent evidence indicates that metformin therapy may be associated with a decreased colorectal adenoma/colorectal cancer risk in type 2 diabetes patients. However, results are not consistent. We therefore performed a systematic review and meta-analysis to assess the association between metformin therapy and risk of colorectal adenomas/colorectal cancer in type 2 diabetes mellitus patients. We searched the literature published before Aug 31, 2016 in four databases: PubMed, Embase database, CNKI and VIP Library of Chinese Journal. Summary risk estimates (adjusted OR/adjusted RR/adjusted HR) with their 95% confidence interval (95% CI) were obtained using a random effects model. Twenty studies (including 12 cohort studies, 7 case-control studies and 1 randomized controlled trial study) were selected in terms of data of colorectal adenomas or colorectal cancer incidence. Metformin therapy was found to be associated with a decreased incidence of colorectal adenomas (unadjusted OR=0.80, 95% CI: 0.71-0.90, p=0.0002). When the adjusted data were analyzed, the summary estimate decreased to 25% reduction in colorectal adenomas risk (adjusted OR=0.75, 95% CI: 0.59-0.97, p=0.03). Besides, a significant reduction of colorectal cancer risk was also observed (unadjusted OR=0.73, 95% CI: 0.62-0.86, p=0.0002). And when the adjusted data were analyzed, colorectal cancer risk for metformin users was decreased with a reduction of 22%, compared with non-metformin users and other treatment users (adjusted OR=0.78, 95% CI: 0.70–0.87, p<0.00001). Our meta-analysis suggested that metformin therapy may be associated with a decreased risk of colorectal adenomas and colorectal cancer in type 2 diabetes mellitus patients.