The impact of diabetes and metformin on clinical outcomes is negligible in risk-adjusted endometrial cancer cohorts

AlHilli, Mariam M.; Bakkum-Gamez, Jamie N.; Mariani, Andrea; Shridhar, Viji; Cliby, B.A.; McGree, M.; Weaver, Amy L.; Dowdy, Sean C.; Podratz, Karl C.

doi:10.1016/j.ygyno.2015.01.391

Cited by 4 publications

(2 citation statements)

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“…The results of this meta-analysis showed that women with diabetes had a 72% increased risk of endometrial cancer compared to those without diabetes as supports the previous meta-analysis conducted by E. Friberg et al (31) in 2007. Also, other studies have shown that diabetes increased the risk of endometrial cancer, which is in line with the results of the present study [5, 6, 16, 23, 26, 32, 35].…”

Section: Discussionsupporting

confidence: 93%

“…1), of which 9 were cohort and population cohort studies [4–6, 16–21] (Table 1) and 13 were case-control and population case-control studies [22–34] (Table 2). Also, 12 studies were conducted in the USA [4, 5, 16, 19, 20, 22, 27, 29–32, 34], 4 in Sweden [17, 18, 21, 33], 2 in Italy [25, 26], 1 in Canada [23], 1 in Norway [6], 1 in Mexico [28], and 1 in Japan [24]. The case-control and population case-control studies ( n = 13) comprised 22,392 controls and 7698 endometrial cancer cases.…”

Section: Resultsmentioning

confidence: 99%

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The effect of diabetes on the risk of endometrial Cancer: an updated a systematic review and meta-analysis

et al. 2019

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Background Previous studies conducted on the association between diabetes and the risk of endometrial cancer have reported controversial results that have raised a variety of questions about the association between diabetes and the incidence of this cancer. Thus, the aim of this systematic review and meta-analysis was to more precisely estimate the effect of diabetes on the risk of endometrial cancer incidence. Methods All original articles were searched in international databases, including Medline (PubMed), Web of sciences, Scopus, EMBASE, and CINHAL. Search was done from January 1990 to January 2018 without language limitations. Also, logarithm and standard error logarithm relative risk (RR) were used for meta-analysis. Results A total of 22 cohort and case-control studies were included in this meta-analysis, of which 14 showed statistically significant associations between diabetes and risk of endometrial cancer. Diabetes was associated with increased risk of endometrial cancer (RR = 1.72, 95% CI 1.48–2.01). The summary of RR for all 9 cohort studies was 1.56 (95% CI 1.21–2.01), and it was 1.85 (95% CI 1.53–2.23) for 13 case control studies. The summary of RR in hospital-based studies was higher than other studies. Thirteen of the primary studies-controlled BMI as a confounding variable, and the combined risk of their results was 1.62 (95% CI 1.34–1.97). Conclusions Diabetes seems to increases the risk of endometrial cancer in women, and this finding can be useful in developing endometrial cancer prevention plans for women having diabetes.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

The effect of diabetes on the risk of endometrial Cancer: an updated a systematic review and meta-analysis

et al. 2019

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Differential Expressions of Ki-67, Bcl-2, and Apoptosis Index in Endometrial Cells of Women With and Without Type II Diabetes Mellitus and Their Correlation with Clinicopathological Variables

et al. 2021

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Prospective evaluation of the molecular effects of metformin on the endometrium in women with newly diagnosed endometrial cancer: A window of opportunity study

Soliman

Zhang

Broaddus

et al. 2016

Gynecologic Oncology

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Objective Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC. Methods In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850 mg daily for ≥7 days, and underwent post-treatment blood draw/definitive surgery. Pre- and post- serum analyses were performed. Tumor samples were evaluated for changes in AMPK, PI3K/AKT pathway, proliferation, and apoptosis by immunohistochemistry. Results Twenty patients completed the trial. Median age and BMI were 57 years (range: 27–67) and 34.5 kg/m2 (range: 21.9–50.0). Median duration of metformin was 9.5 days (range: 7–24). A majority of women had endometrioid adenocarcinomas (90%) and were early stage (85%). After metformin, there were significant decreases in serum IGF-1 (p=0.046), omentin (p=0.007), insulin (p=0.012), C-peptide (p=0.018), and leptin (p=0.0035). Compared to baseline, posttreatment tissue showed decreased phospho-AKT in 18/20 patients (90%, p=0.0002), decreased phospho-S6rp in 14/20 patients (70%, p=0.057), and decreased phospho-p44/42MAPK in 15/18 patients (83.3%, p=0.0038). There was no difference in Ki67, phospho-ACC, or caspase 3. Changes did not correlate with BMI, grade, or KRAS mutation. Conclusion In this prospective window of opportunity study, we demonstrated that relevant serum and molecular changes occur in patients with newly diagnosed EC after a short course of metformin. Ongoing clinical trials will help determine the appropriate role for metformin in the treatment of women with EC.

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The impact of diabetes and metformin on clinical outcomes is negligible in risk-adjusted endometrial cancer cohorts

Cited by 4 publications

References 0 publications

The effect of diabetes on the risk of endometrial Cancer: an updated a systematic review and meta-analysis

The effect of diabetes on the risk of endometrial Cancer: an updated a systematic review and meta-analysis

Differential Expressions of Ki-67, Bcl-2, and Apoptosis Index in Endometrial Cells of Women With and Without Type II Diabetes Mellitus and Their Correlation with Clinicopathological Variables

Prospective evaluation of the molecular effects of metformin on the endometrium in women with newly diagnosed endometrial cancer: A window of opportunity study

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