Metformin in breast cancer: preclinical and clinical evidence

Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer

“…The ability of metformin to promote glucose uptake by the muscles, increase insulin senitivity, reduce insulin levels, and thereby reduce blood glucose levels in itself reduces pre-neoplastic and neoplastic breast cell proliferation [136]. The fact that metformin has remained off patent since 2002, is easy to synthesize and economical, well-tolerated with very little side effects, and works at the level of the whole organism by reducing insulin levels and also directly on the tumor cells makes metformin an interesting drug of choice for the treatment of cancer [137].…”

“…The hurdle, however, lies in the fact that the use of a single treatment modality/monotherapy approach leads to toxicity and the evolution of resistance, metastasis, and relapse of the disease. Much of the research in the field of oncology is now focused on overcoming these obstacles by treating cancers with a combination of one or more drugs or therapeutic modalities, which was found to be advantageous over monotherapies due to a number of reasons [137,164]. Using targeted therapeutic combination regimens translates to (1) higher efficacy of the treatment and improved overall outcome and prognosis, with decreased incidence of metastasis and relapse; (2) synergistic effects of the drugs, therefore requiring combination drugs to be used at much lower dosage but with maximum efficiency; (3) lesser drug induced toxicity and adverse side effects as a result of lower dosage of the drugs when used in combination; and (4) avoidance of resistance development against the drugs when used in combination [165].…”

“…Dosage of metformin administration as a monotherapy or in combination with other drugs or therapeutic modalities is critical to achieve therapeutic efficiency in the treatment with minimal side effects. When used orally in the treatment of diabetes, the anti-hyperglycemic effects of metformin have been reported at plasma concentrations ranging from around from 10-100 µM [68,137,203]. Interestingly, epidemiological, observational, and meta-analysis reports suggest that oral administration of metformin (normal initial oral dose for; 'immediate release' is 500 mg twice/day or 850 mg once/day, with 500 mg increments weekly as tolerated, maximum dose of 2550 mg/day; 'extended release' is 500 to 1000 mg once/day, with 500 mg increments weekly as tolerated, maximum dose of 2000 mg/day) in type 2 diabetic patients significantly reduced the risk of many different cancers when compared to diabetic patients on other anti-hyperglycemic treatment regimens [35,37,204,205].…”

“…Metformin use showed no effect on the incidence of cancers in studies that avoided these biases [201,206]. In the majority of in vitro/cancer cell based experiments, however, metformin treatment-related inhibitory effect on tumor cell proliferation, activation of apoptotic cell death, and inhibition of tumor progression was only observed at >2-5 mM concentrations of metformin [68,137,138,203,207]. Further studies are warranted to provide a clear insight into the possible dose-dependent effect of metformin on cancer prevention/risk reduction in 'diabetic' patients and cancer treatment in 'diabetic-cancer' patients.…”

Therapie des Typ-2-Diabetes

“…1 Lebensstilmodifizierende, nichtmedikamentöse Therapiemaßnahmen stellen auf jeder Therapiestufe die Basistherapie dar, sind aber häufig allein nicht ausreichend. Bei Patienten, bei denen mit lebensstilmodifizierenden Maßnahmen keine ausreichenden Erfolge abzusehen sind (aufgrund von Schweregrad der Stoffwechselentgleisung, Adhärenzproblemen, Multimorbidität), sollten diese Maßnahmen mit Metformin und bei Kontraindikation oder Unverträglichkeit mit einem anderen Antidiabetikum kombiniert werden.min für eine bestimmte Kombinationstherapie im Hinblick auf kardiovaskuläre Endpunkte und Gesamtmortalität[37,38].Metformin gewinnt derzeit aufgrund interessanter pleiotroper Effekte, die Änderungen des Epigenoms und der Genexpression beeinflussen und so potenziell protektiv u. a. gegen Karzinome wirken sollen, großes Interesse[39][40][41][42][43][44].Zusammenfassung zur Therapie mit Metformin: ▪ Die Nierenfunktion muss regelmäßig kontrolliert werden (alle 3-6 Monate). CAVE: Metformin muss sofort abgesetzt werden, wenn die eGFR auf < 30 ml/min.…”