A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density

Tapia, Edgar O.; Villa-Guillen, Diana Evelyn; Chalasani, Pavani; Centuori, Sara; Roe, Denise J.; Guillen-Rodriguez, José; Huang, Chuan; Galons, Jean-Phillippe; Thomson, Cynthia A.; Altbach, María I.; Trujillo, Jesse; Pinto, Liane; Martinez, Jessica A.; Algotar, Amit M.; Chow, H‐H. Sherry

doi:10.1007/s10549-021-06355-9

Cited by 14 publications

(5 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there was a non-signi cant decrease in mean body weight between the metformin arm and the control arm. These results seem consistent with the results reported by Tapia et al 2021 [23].…”

Section: Discussionsupporting

confidence: 94%

Metformin as an adjuvant therapy to an aromatase inhibitor in overweight and obese postmenopausal women with breast cancer: A pilot study

elattar

Ibrahim

Alhassanin

et al. 2022

Preprint

View full text Add to dashboard Cite

Introduction: Metformin may provide therapeutic benefits to patients with various types of malignancy. Through its insulin-sensitizing effect, metformin can also reduce weight in non-diabetic populations.Purpose: Our research aimed at evaluating the effect of metformin as an adjuvant therapy to aromatase inhibitor (letrozole) on estradiol and other biomarkers serum levels in postmenopausal obese breast cancer women.Patients and methods: This controlled study involved 45 postmenopausal breast cancer females who were assigned into three arms: the control arm (arm 1; n= 15 obese women) which received letrozole only (2.5 mg/day); the metformin arm (arm 2; n= 15 obese women) which provided a similar letrozole dosage in addition to metformin (2000 ± 500 mg/day); and the lean arm (arm 3; n= 15) which received letrozole. The intervention duration was 6 months. Blood samples were obtained at zero time and six months later for the measurement of serum estradiol, osteocalcin, insulin, leptin, lactate, and fasting blood glucose. Results: After the intervention, the metformin arm had significantly lower osteocalcin and fasting blood glucose levels than both the control and the lean arms (p<0.0001, p<0.0001, respectively). The metformin and lean arms had significantly lower fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), estradiol, and leptin concentrations than the control arm (p = 0.0064, p = 0.0020, p<0.0001, and p<0.0001, respectively). We observed non-significant variation in serum lactate levels among the three study arms.Conclusion: Metformin might represent a promising adjuvant therapy to letrozole in postmenopausal women with breast cancer.ClinicalTrials.gov Identifier: NCT05053841/Registered September 23, 2021 - Retrospectively

show abstract

Section: Discussionsupporting

confidence: 94%

Metformin as an adjuvant therapy to an aromatase inhibitor in overweight and obese postmenopausal women with breast cancer: A pilot study

elattar

Ibrahim

Alhassanin

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Here, we have included 34 completed clinical trials with results available on the clinicaltrials.gov website among the 182 results searched until March 2023 (Table 1 ). These include brain tumors [ 149 ], HNSCC [ 15 , 22 , 136 , 137 ], acute lymphoblastic leukemia [ 150 ], and breast [ 76 , 77 , 151 – 157 ], lung [ 158 ], esophageal [ 136 , 159 ], colorectal [ 160 , 161 ], pancreatic [ 162 – 164 ], endometrial [ 165 – 169 ], ovarian [ 14 , 170 ], and prostate [ 13 , 171 – 175 ] cancers. Among them, two trials are in phase 3, and 16 trials combine metformin with chemotherapy and/or radiotherapy and/or targeted therapy.…”

Section: Clinical Trialsmentioning

confidence: 99%

Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing

Zheng

Yao

et al. 2023

J Transl Med

View full text Add to dashboard Cite

Metformin is a well-known anti-diabetic drug that has been repurposed for several emerging applications, including as an anti-cancer agent. It boasts the distinct advantages of an excellent safety and tolerability profile and high cost-effectiveness at less than one US dollar per daily dose. Epidemiological evidence reveals that metformin reduces the risk of cancer and decreases cancer-related mortality in patients with diabetes; however, the exact mechanisms are not well understood. Energy metabolism may be central to the mechanism of action. Based on altering whole-body energy metabolism or cellular state, metformin’s modes of action can be divided into two broad, non-mutually exclusive categories: “direct effects”, which induce a direct effect on cancer cells, independent of blood glucose and insulin levels, and “indirect effects” that arise from systemic metabolic changes depending on blood glucose and insulin levels. In this review, we summarize an updated account of the current knowledge on metformin antitumor action, elaborate on the underlying mechanisms in terms of the hallmarks of cancer, and propose potential applications for repurposing metformin for cancer therapeutics.

show abstract

“…An increasing number of epidemiological studies have indicated that, besides the antidiabetic effect, metformin reduces both the incidence and mortality of several types of cancer, including breast cancer where metformin use was associated with a lower incidence of invasive breast cancer in postmenopausal women with type 2 diabetes [ 48 ] and premenopausal women with components of metabolic syndrome [ 49 ]. A meta-analysis indicated that in postmenopausal women with diabetes associated metformin use with a 30% lowered overall incidence of cancer when compared with patients with diabetes receiving other therapies [ 50 ].…”

Section: Cholesterol Biosynthesismentioning

confidence: 99%

De novo cholesterol biosynthesis: an additional therapeutic target for the treatment of postmenopausal breast cancer with excessive adipose tissue

Coradini

2022

Exploration of Targeted Anti-Tumor Therapy

View full text Add to dashboard Cite

The onset and development of breast cancer in postmenopausal women are associated with closely related individual-dependent factors, including weight gain and high levels of circulating androgens. Adipose tissue is the most peripheral site of aromatase enzyme synthesis; therefore, the excessive accumulation of visceral fat results in increased androgens aromatization and estradiol production that provides the microenvironment favorable to tumorigenesis in mammary epithelial cells expressing estrogen receptors (ERs). Moreover, to meet the increased requirement of cholesterol for cell membrane assembly and the production of steroid hormones to sustain their proliferation, ER-positive cells activate de novo cholesterol biosynthesis and subsequent steroidogenesis. Several approaches have been followed to neutralize the de novo cholesterol synthesis, including specific enzyme inhibitors, statins, and, more recently, metformin. Cumulating evidence indicated that inhibiting cholesterol biosynthesis by statins and metformin may be a promising therapeutic strategy to block breast cancer progression. Unlike antiestrogens and aromatase inhibitors (AIs) which compete for binding to ER and inhibit androgens aromatization, respectively, statins block the production of mevalonic acid by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and metformin hampers the activation of the sterol regulatory element-binding protein 2 (SREBP2) transcription factor, thus inhibiting the synthesis of several enzymes involved in cholesterol biosynthesis. Noteworthy, statins and metformin not only improve the prognosis of overweight patients with ER-positive cancer but also improve the prognosis of patients with triple-negative breast cancer, the aggressive tumor subtype that lacks, at present, specific therapy.

show abstract

A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density

Cited by 14 publications

References 56 publications

Metformin as an adjuvant therapy to an aromatase inhibitor in overweight and obese postmenopausal women with breast cancer: A pilot study

Metformin as an adjuvant therapy to an aromatase inhibitor in overweight and obese postmenopausal women with breast cancer: A pilot study

Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing

De novo cholesterol biosynthesis: an additional therapeutic target for the treatment of postmenopausal breast cancer with excessive adipose tissue

Contact Info

Product

Resources

About