SGLT2 inhibitors (SGLT2i) have lately gained popularity as an effective treatment for type 2 diabetes (T2D), with additional benefits due to well-known large trials showing cardiovascular and kidney protection, especially in patients with established chronic kidney disease and heart failure. While SGLT2i have been shown to be effective for treating T2D, there have been concerns about their potential risks, including the risk of cancer. Some studies showed an increased risk of cancer [
], especially for bladder cancer [
- Shi N.
- Shi Y.
- Xu J.
- Si Y.
- Yang T.
- Zhang M.
- et al.
SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. Front.
Public Health. 2021; : 9https://doi.org/10.3389/fpubh.2021.668368
], whereas some others did not find any connection [
- García M.
- Arteche-Martinez U.
- Lertxundi U.
- Aguirre C.
SGLT2 Inhibitors and Bladder Cancer: Analysis of Cases Reported in the European Pharmacovigilance Database.
The Journal of Clinical Pharmacology. 2021; 61: 187-192https://doi.org/10.1002/jcph.1722
- Tang H.
- Dai Q.
- Shi W.
- Zhai S.
- Song Y.
- Han J.
SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.
Diabetologia. 2017; 60: 1862-1872https://doi.org/10.1007/s00125-017-4370-8
- Tang H.
- Yang K.
- Song Y.
- Han J.
Meta-analysis of the association between sodium-glucose co-transporter-2 inhibitors and risk of skin cancer among patients with type 2 diabetes.
Diabetes Obes Metab. 2018; 20: 2919-2924https://doi.org/10.1111/dom.13474
- Dicembrini I.
- Nreu B.
- Mannucci E.
- Monami M.
Sodium-glucose co-transporter-2 (SGLT-2) inhibitors and cancer: A meta-analysis of randomized controlled trials.
Diabetes Obes Metab. 2019; 21: 1871-1877https://doi.org/10.1111/dom.13745
- Pelletier R.
- Ng K.
- Alkabbani W.
- Labib Y.
- Mourad N.
- Gamble J.
The association of sodium-glucose cotransporter 2 inhibitors with cancer: An overview of quantitative systematic reviews. Endocrinol.
Diabetes Metab. 2020;; : 3https://doi.org/10.1002/edm2.145
- Abrahami D.
- Tesfaye H.
- Yin H.
- Vine S.
- Hicks B.
- Yu O.H.Y.
- et al.
Sodium-Glucose Cotransporter 2 Inhibitors and the Short-term Risk of Bladder Cancer: An International Multisite Cohort Study.
Diabetes Care. 2022; 45: 2907-2917https://doi.org/10.2337/dc22-1174
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- SGLT-2i and Risk of Malignancy in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. Front.Public Health. 2021; : 9https://doi.org/10.3389/fpubh.2021.668368
- SGLT2 Inhibitors and Bladder Cancer: Analysis of Cases Reported in the European Pharmacovigilance Database.The Journal of Clinical Pharmacology. 2021; 61: 187-192https://doi.org/10.1002/jcph.1722
- SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.Diabetologia. 2017; 60: 1862-1872https://doi.org/10.1007/s00125-017-4370-8
- Meta-analysis of the association between sodium-glucose co-transporter-2 inhibitors and risk of skin cancer among patients with type 2 diabetes.Diabetes Obes Metab. 2018; 20: 2919-2924https://doi.org/10.1111/dom.13474
- Sodium-glucose co-transporter-2 (SGLT-2) inhibitors and cancer: A meta-analysis of randomized controlled trials.Diabetes Obes Metab. 2019; 21: 1871-1877https://doi.org/10.1111/dom.13745
- The association of sodium-glucose cotransporter 2 inhibitors with cancer: An overview of quantitative systematic reviews. Endocrinol.Diabetes Metab. 2020;; : 3https://doi.org/10.1002/edm2.145
- Sodium-Glucose Cotransporter 2 Inhibitors and the Short-term Risk of Bladder Cancer: An International Multisite Cohort Study.Diabetes Care. 2022; 45: 2907-2917https://doi.org/10.2337/dc22-1174
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors and non-small cell lung cancer survival.Br J Cancer. 2023; https://doi.org/10.1038/s41416-023-02177-2
- Sodium-glucose cotransporter 2 inhibitor canagliflozin attenuates lung cancer cell proliferation in vitro.Diabetol Int. 2021; 12: 389-398https://doi.org/10.1007/s13340-021-00494-6
- Canagliflozin primes antitumor immunity by triggering PD-L1 degradation in endocytic recycling.Journal of Clinical Investigation. 2023; : 133https://doi.org/10.1172/JCI154754
- Sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation and hepatocellular carcinoma prognosis.PLoS One. 2022; 17: e0274519
- Impact of anti-diabetic sodium-glucose cotransporter 2 inhibitors on tumor growth of intractable hematological malignancy in humans.Biomedicine & Pharmacotherapy. 2022; 149112864https://doi.org/10.1016/j.biopha.2022.112864
- Sodium-glucose co-transporter-2 (SGLT-2) inhibition reduces glucose uptake to induce breast cancer cell growth arrest through AMPK/mTOR pathway.Biomedicine & Pharmacotherapy. 2020; 132110821https://doi.org/10.1016/j.biopha.2020.110821
- Empagliflozin mediated miR-128-3p upregulation promotes differentiation of hypoxic cancer stem-like cells in breast cancer.Eur J Pharmacol. 2023; 943175565https://doi.org/10.1016/j.ejphar.2023.175565
- SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation.Endocr J. 2020; 67: 99-106https://doi.org/10.1507/endocrj.EJ19-0428
- An SGLT2 inhibitor modulates SHH expression by activating AMPK to inhibit the migration and induce the apoptosis of cervical carcinoma cells.Cancer Lett. 2020; 495: 200-210https://doi.org/10.1016/j.canlet.2020.09.005
- SGLT2 inhibitor activates the STING/IRF3/IFN-β pathway and induces immune infiltration in osteosarcoma.Cell Death Dis. 2022; 13: 523https://doi.org/10.1038/s41419-022-04980-w
- SGLT2 inhibition restrains thyroid cancer growth via G1/S phase transition arrest and apoptosis mediated by DNA damage response signaling pathways.Cancer Cell Int. 2022; 22: 74https://doi.org/10.1186/s12935-022-02496-z
- SGLT-2 as a potential target in pancreatic cancer: the preliminary clue from The Cancer Genome Atlas data.J Gastrointest Oncol. 2022; 13: 2539-2552https://doi.org/10.21037/jgo-22-900
- SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway via the hnRNPK-YAP1 axis.Cancer Lett. 2021; 519: 277-288https://doi.org/10.1016/j.canlet.2021.07.035
- Exploring the Role of Sodium-Glucose Cotransporter as a New Target for Cancer Therapy.Journal of Pharmacy & Pharmaceutical Sciences. 2022; 25: 253-265https://doi.org/10.18433/jpps32879
- Repurposing sodium-glucose co-transporter 2 inhibitors (SGLT2i) for cancer treatment – A Review.Rev Endocr Metab Disord. 2021; 22: 1121-1136https://doi.org/10.1007/s11154-021-09675-9
- Impact of sodium-glucose cotransporter-2 inhibitors on heart failure and mortality in patients with cancer.Heart. 2023; 109: 470-477https://doi.org/10.1136/heartjnl-2022-321545
- Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients.Arch Toxicol. 2021; 95: 659-671https://doi.org/10.1007/s00204-020-02951-8
Gongora CA, Drobni ZD, Quinaglia Araujo Costa Silva T, Zafar A, Gong J, Zlotoff DA, et al. Sodium-Glucose Co-Transporter-2 Inhibitors and Cardiac Outcomes Among Patients Treated With Anthracyclines. JACC Heart Fail 2022;10:559–67. https://doi.org/10.1016/j.jchf.2022.03.006.
- Effects of novel SGLT2 inhibitors on cancer incidence in hyperglycemic patients: a meta-analysis of randomized clinical trials.Pharmacol Res. 2022; 175106039https://doi.org/10.1016/j.phrs.2021.106039
- GLP-1 Receptor Agonists and the Risk of Thyroid Cancer.Diabetes Care. 2023; 46: 384-390https://doi.org/10.2337/dc22-1148
- Glucagon-Like Peptide-1 Receptor Agonists Activate Rodent Thyroid C-Cells Causing Calcitonin Release and C-Cell Proliferation.Endocrinology. 2010; 151: 1473-1486https://doi.org/10.1210/en.2009-1272
- GLP-1 and Calcitonin Concentration in Humans: Lack of Evidence of Calcitonin Release from Sequential Screening in over 5000 Subjects with Type 2 Diabetes or Nondiabetic Obese Subjects Treated with the Human GLP-1 Analog.Liraglutide. J Clin Endocrinol Metab. 2011; 96: 853-860https://doi.org/10.1210/jc.2010-2318
- A meta-analysis of serious adverse events reported with exenatide and liraglutide: Acute pancreatitis and cancer.Diabetes Res Clin Pract. 2012; 98: 271-284https://doi.org/10.1016/j.diabres.2012.09.008
- Thyroid safety in patients treated with liraglutide.J Endocrinol Invest. 2013; 36: 140-145https://doi.org/10.1007/BF03346749
- Expression of GLP-1 receptor and CD26 in human thyroid C-cells: The association of thyroid C-cell tumorigenesis with incretin-based medicine.Oncol Lett. 2017; 13: 2684-2690https://doi.org/10.3892/ol.2017.5752
- Thyroid neoplasms after therapeutic radiation for malignancies during childhood or adolescence.Cancer. 2003; 97: 2397-2403https://doi.org/10.1002/cncr.11362
- Balancing the benefits and harms of thyroid cancer surveillance in survivors of Childhood, adolescent and young adult cancer: Recommendations from the international Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium.Cancer Treat Rev. 2018; 63: 28-39https://doi.org/10.1016/j.ctrv.2017.11.005
- Putting GLP-1 RAs and Thyroid Cancer in Context: Additional Evidence and Remaining Doubts.Diabetes Care. 2023; 46: 249-251https://doi.org/10.2337/dci22-0052
- A Comparison of the Burden of Thyroid Cancer Among the European Union 15+ Countries, 1990–2019.JAMA Otolaryngology-Head & Neck Surgery. 2022; 148: 350https://doi.org/10.1001/jamaoto.2021.4549
- Nutritional status and follicular-derived thyroid cancer: An update.Crit Rev Food Sci Nutr. 2021; 61: 25-59https://doi.org/10.1080/10408398.2020.1714542
- The impact of family history on non-medullary thyroid cancer.European Journal of Surgical Oncology (EJSO). 2016; 42: 1455-1463https://doi.org/10.1016/j.ejso.2016.08.006
- Clinically Silent Thyroid Cancers: Drop Those Needles and Scalpels!.J Clin Endocrinol Metab. 2020; 105: e889-e890https://doi.org/10.1210/clinem/dgz129
- 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.Thyroid. 2016; 26: 1-133https://doi.org/10.1089/thy.2015.0020
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