MateoBeach posted on SGLT2 inhibitors a year ago. Now three more studies show promise for prostate cancer. Note that the last study is a preprint.
Pharmacological targets of SGLT2 inhibition on prostate cancer mediated by circulating metabolites: A drug-target Mendelian randomization study
Y Lin, Y Zhang, S Wang, L Cao, R Zhao, X Ma… - Frontiers in …, 2024 - frontiersin.org
Front. Pharmacol., 06 August 2024
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi.org/10.3389/fphar.2024....
“Background: The relationship between sodium-glucose cotransporter 2 (SGLT2) inhibitors and prostate cancer is still unknown. Although these inhibitors can influence tumor glycolysis, the underlying mechanism requires further exploration.
Methods: A two-sample two-step MR was used to determine 1) causal effects of SGLT2 inhibition on prostate cancer; 2) causal effects of 1,400 circulating metabolites or metabolite ratios on prostate cancer; and 3) mediation effects of these circulating metabolites. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene and glycated hemoglobin level (HbA1c). Additionally, positive control analysis on type 2 diabetes mellitus (T2DM) was conducted to test the selection of genetic proxies. Phenome Wide Association Study (PheWAS) and MR-PheWAS analysis were used to explore potential treatable diseases and adverse outcomes of SGLT2 inhibitors.
Results: Genetically predicted SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of T2DM [odds ratio (OR) = 0.66 (95% CI 0.53, 0.82), P = 1.57 × 10−4]; prostate cancer [0.34 (0.23, 0.49), P = 2.21 × 10−8] and prostate-specific antigen [0.26 (0.08, 0.81), P = 2.07 × 10−2]. The effect of SGLT2 inhibition on prostate cancer was mediated by uridine level, with a mediated proportion of 9.34% of the total effect. In MR-PheWAS, 65 traits were found to be associated with SLGT2 inhibitors (P < 1.78 × 10−5), and among them, 13 were related to diabetes.
Conclusion: Our study suggested that SGLT2 inhibition could lower prostate cancer risk through uridine mediation. More mechanistic and clinical research is necessary to explore how uridine mediates the link between SGLT2 inhibition and prostate cancer.”
The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data
J Zheng, J Lu, J Qi, Q Yang, H Zhao, H Liu, Z Chen… - Cell Reports …, 2024 - cell.com
Publication History:
Received February 1, 2024; Revised June 29, 2024;
DOI: 10.1016/j.xcrm.2024.101688
“Summary
We evaluated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on prostate cancer by evidence triangulation. Using Mendelian randomization, we found that genetically proxied SGLT2 inhibition reduced the risk of overall (odds ratio = 0.56, 95% confidence interval [CI] = 0.38 to 0.82; 79,148 prostate cancer cases and 61,106 controls), advanced, and early-onset prostate cancer. Using electronic healthcare data (nSGLT2i = 24,155; nDPP4i = 24,155), we found that the use of SGLT2 inhibitors was associated with a 23% reduced risk of prostate cancer (hazard ratio = 0.77, 95% CI = 0.61 to 0.99) in men with diabetes. Using data from two prospective cohorts (n4C = 57,779; nUK_Biobank = 165,430), we found little evidence to support the association of HbA1c with prostate cancer, implying a non-glycemic effect of SGLT2 inhibition on prostate cancer. In summary, this study provides multiple layers of evidence to support the beneficial effect of SGLT2 inhibition on reducing prostate cancer risk. Future trials are warranted to investigate whether SGLT2 inhibitors can be recommended for prostate cancer prevention.”
Genetic associations between SGLT2 inhibition, DPP4 inhibition or GLP1R agonism and prostate cancer risk: a two-sample Mendelian randomisation study
L Shen, Y Yang, L Lu, OHI Chou, Q Lee, T Liu, G Li… - medRxiv, 2024 - medrxiv.org
doi: doi.org/10.1101/2024.09.15....
”Conclusions
The two-sample MR analysis found that SGLT2 and DPP4 inhibition, but not GLP1R agonism, was associated with lower risks of developing prostate cancer.”
The Warburg Effect [an increase in the rate of glucose uptake and preferential production of lactate, even in the presence of oxygen.]
Unmetabolized Estrogen (Depurinated Adducts) How I got PCa and how to prevent and detect it.
