Metformin Treatment for Diabetes Mellitus Correlates with Progression and Survival in Colorectal Carcinoma

Powell, Marta K.; Cempirkova, Dana; Dundr, Pavel; Grimmichova, Tereza; Třebický, Ferdinand; Brown, Robert E.; Gregorová, Jana; Litschmannová, Martina; Janurová, Kateřina; Pešta, Michal; Heneberg, Petr

doi:10.1016/j.tranon.2019.10.011

Cited by 17 publications

(9 citation statements)

References 46 publications

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“…Data concerning potential uses of metformin as an adjuvant treatment in patients who have already developed colorectal cancer are even more scarce: while a series of published papers suggest that metformin use might be associated with improved survival [ 85 , 86 , 87 , 88 ], in all these studies, the number of patients with unresected metastatic disease is rather low (usually lower than 3–4% of the whole patient population).…”

Section: Resultsmentioning

confidence: 99%

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

Cantini

Giglio

Bittoni

et al. 2020

Cancers

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Colorectal cancer is characterized by high incidence worldwide. Despite increased awareness and early diagnosis thanks to screening programmes, mortality remains high, particularly for patients with metastatic involvement. Immune checkpoint inhibitors or poly (ADP-ribose) polymerase (PARP)-inhibitors have met with disappointing results when used in this setting, opposed to other malignancies. New drugs with different mechanisms of action are needed in this disease. Drug repurposing might offer new therapeutic options, as patients with metastatic colorectal cancer often share risk factors for other chronic diseases and thus frequently are on incidental therapy with these drugs. The aim of this review is to summarise the published results of the activity of drugs used to treat chronic medications in patients affected by colorectal cancer. We focused on antihypertensive drugs, Non-Steroid Anti-inflammatory Drugs (NSAIDs), metformin, antidepressants, statins and antibacterial antibiotics. Our review shows that there are promising results with beta blockers, statins and metformin, whereas data concerning antidepressants and antibacterial antibiotics seem to show a potentially harmful effect. It is hoped that further prospective trials that take into account the role of these drugs as anticancer medications are conducted.

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Section: Resultsmentioning

confidence: 99%

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

Cantini

Giglio

Bittoni

et al. 2020

Cancers

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“…Recently, in cancer cells it has been demonstrated that metformin possess anti-tumorigenic properties and proven to inhibit cell proliferation, invasion and migration in most of the cancer cells. It appears to affect multiple key processes related to cell growth, proliferation, and survival [27][28][29][30]. To proceed with our hypothesis, Metformin, Vemurafenib and 5-Azacytidine were docked with TSHR protein using iGEMDock software to determine the docking scores in which the protein-ligand interaction were successful in identifying that the drugs were docked with TSHR with common binding site sharing between metformin and vemurafenib.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Effect of Metformin and Vemurufenib (PLX4032) as a Molecular Targeted Therapy in Anaplastic Thyroid Cancer – An In Vitro Study

Durai

Ravindran

Karunagaran

et al. 2021

Preprint

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Survival rate of patients with anaplastic thyroid carcinoma (ATC) is less than 5% with current treatment. Deregulated cell signaling pathways such as BRAF/MAPK/ERK pathway and AMPK pathway along with suppression of iodine metabolising genes including NIS and TSHR are seen in ATC. In ATC, BRAFV600E mutation is the major mutation occurring in ATC that constitutively activate MAPK/ERK signaling and result in the transformation of normal cells in to undifferentiated cancer cells. Although Vemurufenib is a selective oral drug for the BRAFV600E mutant kinase with a response rate of nearly 50% in metastatic melanoma, our study on ATC has showed resistance to Vemurafenib. Metformin, a diabetic drug is an AMPK activator and has recently proved to be involved in preventing or treating several types of cancer. Using iGEMDock software, a protein-ligand interaction was successful between Metformin and TSHR in our study and demonstrated that combination of Vemurufenib with metformin has synergistic anti-cancer effects and provide the evidence that the combination of drugs suppressed the progression of ATC cells growth by inducing significant apoptosis through downregulation of ERK signaling, upregulation of AMPK pathway and by reversing epithelial-mesenchymal transition (EMT) markers - E-cadherin and Vimentin expression. Our results suggest that Metformin act as a demethylating agent in anaplastic thyroid cancer cells by inducing the expression of NIS and TSHR. cAMP signaling has been studied in ATC for the first time through our study wherein cAMP signaling is downregulated due to decrease in intracellular cAMP level upon metformin treatment. To conclude, our findings demonstrate novel therapeutic targets and treatment strategies for undifferentiated ATC.

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“…However, to achieve and maintain specific glycemic targets, the majority of patients require glucose-lowering drugs. Metformin is currently the first-line and widely used pharmacological therapy for patients with T2DM because of its potential benefits, including cardioprotective effect, loss of weight, and prevention of some comorbid diseases 15 – 22 . If lifestyle interventions and a maximally tolerated dose of metformin fail to achieve the glycemic target within 3 months follow-up, the regimen would be changed to combination therapy 15 .…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular safety and efficacy of metformin-SGLT2i versus metformin-sulfonylureas in type 2 diabetes: systematic review and meta-analysis of randomized controlled trials

Gebrie

Getnet

Manyazewal

2021

Sci Rep

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Diabetes is a serious threat to global health and among the top 10 causes of death, with nearly half a billion people living with it worldwide. Treating patients with diabetes tend to become more challenging due to the progressive nature of the disease. The role and benefits of combination therapies for the management of type 2 diabetes are well-documented, while the comparative safety and efficacy among the different combination options have not been elucidated. We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin-sodium-glucose cotransporter-2 inhibitors versus metformin-sulfonylureas in patients with type 2 diabetes. We searched MEDLINE-PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 15 August 2019 without restriction in the year of publication. We included randomized controlled trials of patients with type 2 diabetes who were on metformin-sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year. The primary endpoints were all-cause mortality and serious adverse events, and the secondary endpoints were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hypoglycemia, and changes in glycated hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, blood pressure, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We used a random-effects meta-analysis model to estimate mean differences for continuous outcomes and risk ratio for dichotomous outcomes. We followed PICOS description model for defining eligibility and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for reporting results. Of 3,190 citations, we included nine trials involving 10,974 participants. The pooled analysis showed no significant difference in all-cause mortality (risk ration [RR] = 0.93, 95% CI [0.52, 1.67]), serious adverse events (RR = 0.96, 95% CI [0.79, 1.17]) and adverse events (RR = 1.00, 95% CI [0.99, 1.02]) between the two, but in hypoglycemia (RR = 0.13, 95% CI [0.10, 0.17], P < 0.001). Participants taking metformin-sodium glucose cotransporter-2 inhibitors showed a significantly greater reduction in HbA1c (mean difference [MD] = − 0.10%, 95% CI [− 0.17, − 0.03], body weight (MD = − 4.57 kg, 95% CI [− 4.74, − 4.39], systolic blood pressure (MD = − 4.77 mmHg, 95% CI [− 5.39, − 4.16]), diastolic blood pressure (MD = − 2.07 mmHg, 95% CI [− 2.74, − 1.40], and fasting plasma glucose (MD = − 0.55 mmol/L, 95% CI [− 0.69, − 0.41]), p < 0.001. Combination therapy of metformin and sodium-glucose cotransporter-2 inhibitors is a safe and efficacious alternative to combination therapy of metformin and sulphonylureas for patients with type 2 diabetes who are at risk of cardiovascular comorbidity. However, there remains a need for additional long-term randomized controlled trials as available studies are very limited and heterogeneous.

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Metformin Treatment for Diabetes Mellitus Correlates with Progression and Survival in Colorectal Carcinoma

Cited by 17 publications

References 46 publications

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

Synergistic Effect of Metformin and Vemurufenib (PLX4032) as a Molecular Targeted Therapy in Anaplastic Thyroid Cancer – An In Vitro Study

Cardiovascular safety and efficacy of metformin-SGLT2i versus metformin-sulfonylureas in type 2 diabetes: systematic review and meta-analysis of randomized controlled trials

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