A randomized phase 2 study of bicalutamide with or without metformin for biochemical recurrence in overweight or obese prostate cancer patients (BIMET-1)

Bilušić, Marijo; Toney, Nicole J; Donahue, Renee N.; Wróblewski, Susan; Zibelman, Matthew R.; Ghatalia, Pooja; Ross, Eric A.; Karzai, Fatima; Madan, Ravi A.; Dahut, William L.; Gulley, James L.; Schlom, Jeffrey; Plimack, Elizabeth R.; Geynisman, Daniel M.

doi:10.1038/s41391-022-00492-y

Cited by 14 publications

(11 citation statements)

References 26 publications

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“…A total of 16 RCTs reported on the change in BMI ( n = 2113 on MTF, n = 2252 on placebo/control, mean baseline BMI 25.7−35 kg/m 2 , MTF dose 500–2550 mg/day, intervention duration 3 months to 5 years). The pooled analysis showed an MD in change in BMI of −0.56 (95% CI −0.74, −0.37) kg/m 2 ( I 2 = 78%), favouring MTF 46,48,52,53,56,58,61,66,68,69,73,76,79,82–84 (Figure 3). Prespecified subgroup analysis did not show a significant difference according to the presence or absence of concomitant LSM, as a co‐intervention (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta‐analysis of randomized controlled trials

Haber,

Zarzour,

Ghezzawi

et al. 2024

Diabetes Obesity Metabolism

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There are conflicting data on the weight‐reducing potential of metformin (MTF) in nondiabetic patients with obesity. The purpose of this systematic review and meta‐analysis was to evaluate the effect of MTF on weight and cardiometabolic parameters in adults with overweight/obesity with or without nonalcoholic fatty liver disease (NAFLD) (CRD42018085512). We included randomized controlled trials (RCTs) in adults without diabetes mellitus, with mean body mass index (BMI) ≥ 25 kg/m2, with or without NAFLD, comparing MTF to placebo/control, lifestyle modification (LSM) or a US Food and Drug Administration‐approved anti‐obesity drug, reporting on weight or metabolic parameters, and extending over at least 3 months. We conducted a systematic search in MEDLINE, EMBASE, PubMed and the Cochrane Library without time limitation (until March 2022). We screened and selected eligible articles, abstracted relevant data, and assessed the risk of bias. All steps were in duplicate and independently. We conducted a random‐effects model meta‐analysis using Review Manager version 5.3, with prespecified subgroup analyses in case of heterogeneity. We identified 2650 citations and included 49 trials (55 publications). Compared to placebo, MTF was associated with a significant reduction in BMI (mean difference [MD] −0.56 [−0.74, −0.37] kg/m2; p < 0.0001), at doses ranging from 500 to 2550 mg/day, and with a significant percentage change in BMI of −2.53% (−2.90, −2.17) at the dose 1700 mg/day. There was no interaction by baseline BMI, MTF dose or duration, nor presence or absence of NAFLD. There was no significant difference between MTF and LSM. Orlistat was more effective than MTF (at doses of 1000–1700 mg/day) in terms of weight loss, with an MD in BMI of −3.17 (−5.88; −0.47) kg/m2, favouring the former. Compared to placebo/control, MTF improved insulin parameters, while no effect was detected when compared to LSM. A few small trials showed heterogenous effects on liver parameters in patients with NAFLD treated with MTF compared to placebo/control. There was a large variability in the expression of outcome measures and RCTs were of low quality. In conclusion, MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high‐quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD.

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Section: Resultsmentioning

confidence: 99%

The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta‐analysis of randomized controlled trials

Haber,

Zarzour,

Ghezzawi

et al. 2024

Diabetes Obesity Metabolism

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“…Clinical studies in metastatic, castration-resistant prostate cancer patients show that the addition of metformin is not able to rescue resistance to anti-androgen agent, abiraterone [ 30 ], nor is it able to improve survival or response outcomes when combined with a chemotherapy agent, docetaxel [ 31 ]. A recent trial combining metformin with a different anti-androgen agent, bicalutamide, in overweight and obese prostate cancer patients found that this paired treatment had no effect on PSA levels compared to bicalutamide alone [ 32 ].…”

Section: Metformin In Cancermentioning

confidence: 99%

Metformin and Cancer, an Ambiguanidous Relationship

et al. 2022

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The deregulation of energetic and cellular metabolism is a signature of cancer cells. Thus, drugs targeting cancer cell metabolism may have promising therapeutic potential. Previous reports demonstrate that the widely used normoglycemic agent, metformin, can decrease the risk of cancer in type 2 diabetics and inhibit cell growth in various cancers, including pancreatic, colon, prostate, ovarian, and breast cancer. While metformin is a known adenosine monophosphate-activated protein kinase (AMPK) agonist and an inhibitor of the electron transport chain complex I, its mechanism of action in cancer cells as well as its effect on cancer metabolism is not clearly established. In this review, we will give an update on the role of metformin as an antitumoral agent and detail relevant evidence on the potential use and mechanisms of action of metformin in cancer. Analyzing antitumoral, signaling, and metabolic impacts of metformin on cancer cells may provide promising new therapeutic strategies in oncology.

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“…Bicalutamide with or without metformin for biochemical recurrence in overweight or obese prostate cancer Patients (BIMET-1) [ 176 ]…”

Section: Metformin and Modulation Of The Immune Systemmentioning

confidence: 99%

The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors

2022

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Tumor-infiltrated lymphocytes are exposed to many toxic metabolites and molecules in the tumor microenvironment (TME) that suppress their anti-tumor activity. Toxic metabolites, such as lactate and ketone bodies, are produced mainly by catabolic cancer-associated fibroblasts (CAFs) to feed anabolic cancer cells. These catabolic and anabolic cells make a metabolic compartment through which high-energy metabolites like lactate can be transferred via the monocarboxylate transporter channel 4. Moreover, a decrease in molecules, including caveolin-1, has been reported to cause deep metabolic changes in normal fibroblasts toward myofibroblast differentiation. In this context, metformin is a promising drug in cancer therapy due to its effect on oncogenic signal transduction pathways, leading to the inhibition of tumor proliferation and downregulation of key oncometabolites like lactate and succinate. The cross-feeding and metabolic coupling of CAFs and tumor cells are also affected by metformin. Therefore, the importance of metabolic reprogramming of stromal cells and also the pivotal effects of metformin on TME and oncometabolites signaling pathways have been reviewed in this study.

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A randomized phase 2 study of bicalutamide with or without metformin for biochemical recurrence in overweight or obese prostate cancer patients (BIMET-1)

Cited by 14 publications

References 26 publications

The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta‐analysis of randomized controlled trials

The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta‐analysis of randomized controlled trials

Metformin and Cancer, an Ambiguanidous Relationship

The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors

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