Antidiabetic Therapies Affect Risk of Pancreatic Cancer

Li, Donghui; Yeung, Sai‐Ching Jim; Hassan, Manal M.; Konopleva, Marina; Abbruzzese, James L.

doi:10.1053/j.gastro.2009.04.013

Cited by 541 publications

(445 citation statements)

References 33 publications

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“…Our findings are in line with those of several other epidemiological studies [28][29][30][31][32]. An earlier case-control study by Evans et al found that metformin was associated with a statistically significant 23% reduction in the risk of cancer compared with sulfonylurea therapy among patients with type 2 diabetes, after adjusting for various clinical factors [28].…”

Section: Discussionsupporting

confidence: 92%

“…Similarly, Li et al found that insulin and insulin secretagogue use were associated with an increased risk of pancreatic cancer, whereas metformin use was associated with a reduced risk of pancreatic cancer [30]. Yang et al found that chronic exogenous insulin therapy was associated with a significantly increased risk of colorectal cancer among patients with type 2 diabetes; this increased risk of colorectal cancer was relative to non-insulin users, many of whom were on metformin.…”

Section: Discussionmentioning

confidence: 98%

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Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure

et al. 2010

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Aims/hypothesis We explored the relationship between glucose-lowering agents and cancer mortality rates in type 2 diabetes patients, hypothesising a decreased risk of cancer mortality with metformin use and a dose-risk gradient for insulin therapy. Methods This was a population-based cohort study using administrative data from Saskatchewan Health, Canada. We identified new users of metformin or sulfonylureas from 1 January 1991 to 31 December 1996, with follow-up until death, departure from the province or 31 December 1999. Cox regression analyses were used to estimate the HR of death from cancer, accounting for time-varying exposure to metformin, sulfonylurea, and exogenous insulin therapy. Results We identified 10,309 new users of metformin or sulfonylurea. The average follow-up was 5.4 (1.9) years, during which 407 (4.0%) cancer deaths occurred. Adjusting for age, sex and chronic disease score, the adjusted HR for metformin use was 0.80 (95% CI 0.65-0.98) compared with sulfonylurea monotherapy users. Adjusted HRs for subsequent insulin use were 2.22 (0.99-5.00), 3.33 (2.26-4.89) and 6.40 (4.69-8.73) for <3, 3 to 11 and ≥12 insulin dispensations/year, respectively, compared with patients not on insulin. We observed a similar risk gradient among the sub-cohort of new insulin users. Conclusions/interpretation Our results support previous reports of a decreased risk of cancer outcomes associated with metformin use relative to sulfonylurea monotherapy.We also provide new evidence of a gradient of cumulative insulin dispensations and cancer mortality rates.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure

et al. 2010

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“…Pancreatic cancer was reported in 5 patients in the saxagliptin arm and 12 (including 1 with neuroendocrine tumor) in the placebo arm (Fisher exact test P = 0.09). Although a reduction in pancreatic cancer risk has been suggested for antidiabetic drugs like metformin (32,33), such a protective effect is not assumed for saxagliptin. However, concerns about an increased pancreatic cancer or neuroendocrine tumor risk, as proposed by others in patients under relatively short exposure to DPP-4 inhibitors (2), could not be confirmed in the current study.…”

Section: Discussionmentioning

confidence: 99%

Incidence of Pancreatitis and Pancreatic Cancer in a Randomized Controlled Multicenter Trial (SAVOR-TIMI 53) of the Dipeptidyl Peptidase-4 Inhibitor Saxagliptin

et al. 2014

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OBJECTIVETo determine the incidence of pancreatitis and pancreatic cancer in the SAVOR-TIMI 53 trial. RESEARCH DESIGN AND METHODSA total of 16,492 type 2 diabetic patients ‡40 years old with established cardiovascular (CV) disease or CV risk factors were randomized to saxagliptin or placebo and followed for 2.1 years. Outcome measures were investigator reported with blinded expert adjudication of total pancreatitis (acute and chronic) and reported cases of pancreatic cancer. No differences in time to event onset, concomitant risk factors for pancreatitis, investigatorreported causality from study medication or disease severity, and outcome were found between treatment arms. The investigators reported 5 and 12 cases of pancreatic cancer in the saxagliptin and placebo arms, respectively ], P = 0.09). RESULTS Trial investigators reported CONCLUSIONSIn the SAVOR-TIMI 53 trial, within 2.1 years of follow-up, risk for pancreatitis in type 2 diabetic patients treated with saxagliptin was low and apparently similar to placebo, with no sign of increased risk for pancreatic cancer. Further studies are needed to completely resolve the pancreatic safety issues with incretin-based therapy.

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“…A total of 13 articles (34-46) were retrieved and checked for relevance in terms of intervention, population studied, and reporting of cancer incidence data. Eight of these articles were not included in the meta-analysis for the following reasons: (a) two referred to the same study cohort: Evans et al (35) presented a subset of patients included in a study published later (36), and Jecht (37) published in a German language journal the results already presented in English by Libby et al (36); (b) six did not report overall cancer incidence but data on a single organ site, that is, pancreatic cancer (38), hepatocellular cancer (HCC; refs. 34,45), breast (46), prostate (39), and colorectal cancer (40).…”

Section: Methodsmentioning

confidence: 99%

“…Metformin has been associated with cancer risk reduction in recent epidemiologic studies in diabetic patients (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). With these premises, we performed a systematic review and meta-analysis of available studies to better define the effect of metformin on cancer incidence and mortality in diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis

DeCensi

Puntoni

Goodwin

et al. 2010

Cancer Prevention Research

823

569

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Metformin, an insulin-lowering agent, has been associated with decreased cancer risk in epidemiologic studies in diabetic patients. We performed a comprehensive literature search and meta-analysis of epidemiologic studies to assess the effect of metformin on cancer incidence and mortality in diabetic patients, using Pubmed, ISI Web of Science, Embase, and the Cochrane library until May 2009, with no language or time restrictions. Independent reports with sufficient information to allow risk estimation of cancer risk/mortality and a measure of uncertainty were reviewed and cross-checked independently by three investigators. Eleven studies were selected for relevance in terms of intervention, population studied, independence, and reporting of cancer incidence or mortality data, reporting 4,042 cancer events and 529 cancer deaths. A 31% reduction in overall summary relative risk (0.69; 95% confidence interval, 0.61-0.79) was found in subjects taking metformin compared with other antidiabetic drugs. The inverse association was significant for pancreatic and hepatocellular cancer, and nonsignificant for colon, breast, and prostate cancer. A trend to a dose-response relationship was noted. Metformin is associated with a decreased risk of cancer incidence compared with other treatments among diabetic patients. Given the retrospective nature of most studies and the possibility that the control treatments increase risk, phase II trials are needed before large cancer prevention trials are launched. Cancer Prev Res; 3(11); 1451-61. ©2010 AACR.

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Antidiabetic Therapies Affect Risk of Pancreatic Cancer

Cited by 541 publications

References 33 publications

Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure

Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure

Incidence of Pancreatitis and Pancreatic Cancer in a Randomized Controlled Multicenter Trial (SAVOR-TIMI 53) of the Dipeptidyl Peptidase-4 Inhibitor Saxagliptin

Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis

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