Three‐year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin

Monami, Matteo; Luzzi, Chiara; Lamanna, Caterina; Chiasserini, Veronica; Addante, Filomena; Desideri, Carla Maria; Masotti, Giulio; Marchionni, Niccolò; Mannucci, Edoardo

doi:10.1002/dmrr.642

Cited by 103 publications

(79 citation statements)

References 23 publications

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“…Both classes of agents increase insulin levels, and sulfonylureas have been associated with higher cancer risk (41,60,61). Likewise, insulin, particularly glargine, has been associated with an increased cancer risk in some (62)(63)(64)(65), but not all (66,67), epidemiologic studies; thus, the true protective effect of metformin cannot be estimated.…”

Section: Discussionmentioning

confidence: 99%

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

DeCensi

Puntoni

Goodwin

et al. 2010

Cancer Prevention Research

826

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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Section: Discussionmentioning

confidence: 99%

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

DeCensi

Puntoni

Goodwin

et al. 2010

Cancer Prevention Research

826

569

View full text Add to dashboard Cite

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“…Sulfonylurea has been associated with elevated cancer risk [27,32,[51][52][53], but this might due to the nature of the comparator group. A large portion of patients who were not on therapy with sulfonylurea (that is, those included in the reference ther- reference therapies by study design.…”

Section: Discussionmentioning

confidence: 99%

Cancer Risk Associated with Use of Metformin and Sulfonylurea in Type 2 Diabetes: A Meta-Analysis

et al. 2012

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Objective. Oral antidiabetic drugs (including metformin and sulfonylurea) may play a role in the relationship between type 2 diabetes and cancer. To quantify the association between metformin and sulfonylurea and the risk of cancer, we performed a meta-analysis of available studies on the issue.Materials and Methods. We performed a MEDLINE search for observational studies that investigated the risk of all cancers and specific cancer sites in relation to use of metformin and/or sulfonylurea among patients with type 2 diabetes mellitus. Fixed-and random-effect models were fitted to estimate the summary relative risk (RR). Betweenstudy heterogeneity was tested using 2 statistics and measured with the I 2 statistic. Publication bias was evaluated using funnel plot and Egger's regression asymmetry test.Results.

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“…Importantly, although the concept of combination therapy with metformin and insulin secretagogues is intriguing, it must be accepted only with great caution due to the increased mortality in patients who received such therapy in the UKPDS (30). However, recently Monami et al published retrospective data suggesting that, even after adjusting for known confounders related to disease severity and co-morbidity, glibenclamide (the insulin secretagogue used in the UKPDS) in combination with metformin was associated with a higher mortality compared with repaglinide or other insulin secretagogues in combination with metformin therapy (64). The mechanism behind this finding was proposed to be an w100-fold higher binding to the sulphonylurea receptors with glibenclamide compared with repaglinide (65).…”

Section: Discussionmentioning

confidence: 99%

Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes

Lund

Tarnow

Stehouwer

et al. 2008

European Journal of Endocrinology

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Objective: In patients with type 2 diabetes mellitus (T2DM), biomarkers reflecting inflammation and endothelial dysfunction have been linked to cardiovascular disease (CVD biomarkers) and metabolic regulation. In T2DM patients, metformin and insulin secretagogues have demonstrated equal antihyperglycaemic potency. Here, we report the effect of metformin versus an insulin secretagogue, repaglinide, on CVD biomarkers in non-obese T2DM patients. Design and methods: Single-centre, double-masked, double-dummy, crossover study during 2!4 months involving 96 non-obese (body mass index%27 kg/m 2 ) insulin-naïve T2DM patients. At enrolment, previous oral hypoglycaemic agents were stopped and the patients entered a 1-month runin on diet-only treatment. Hereafter, patients were randomized to either 2 mg repaglinide thrice daily followed by 1 g metformin twice daily or vice versa each during 4 months with a 1-month washout between interventions. Results: Levels of tumour necrosis factor-a, plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, von Willebrand factor, soluble intercellular adhesion molecule-1 and soluble E-selectin were significantly lower during metformin versus repaglinide treatments. In contrast, Amadori albumin and heart rate were higher during metformin versus repaglinide. Levels of interleukin-6, fibrinogen, soluble vascular cell adhesion molecule-1, asymmetric dimethylarginine and advanced glycation end products as well as glycaemic levels (previously reported) and 24-h blood pressure were similar between treatments. Adjustment for known macrovascular disease did not affect the between-treatment effects. Conclusions: In non-obese T2DM patients, metformin was more effective in reducing selected biomarkers reflecting inflammation and endothelial dysfunction compared with repaglinide despite similar glycaemic levels between treatments.European Journal of Endocrinology 158 631-641

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Three‐year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin

Cited by 103 publications

References 23 publications

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

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

Cancer Risk Associated with Use of Metformin and Sulfonylurea in Type 2 Diabetes: A Meta-Analysis

Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes

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