Sodium-glucose cotransporter-2 inhibitors and cancer outcomes: A systematic review and meta-analysis of randomized controlled trials

• Published in: Diabetes research and clinical practice 2023-04, Vol.198, p.110621-110621, Article 110621
• Main Authors: Spiazzi, Bernardo F., Naibo, Rafaella A., Wayerbacher, Laura F., Piccoli, Giovana F., Farenzena, Laura P., Londero, Thizá M., da Natividade, Gabriella R., Zoldan, Maira, Degobi, Nathália A.H., Niches, Matheus, Lopes, Gilberto, Boyko, Edward J., Utzschneider, Kristina M., Colpani, Verônica, Gerchman, Fernando
• Format: Article
• Language: English
• Subjects: Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Glucose; Heart failure; Humans; Hypoglycemic Agents - adverse effects; Neoplasms; Neoplasms - complications; Neoplasms - drug therapy; Randomized Controlled Trials as Topic; Renal insufficiency; Sodium; Sodium-glucose transporter 2 inhibitors; Sodium-Glucose Transporter 2 Inhibitors - adverse effects
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/j.diabres.2023.110621

•Data on malignancy risk with SGLT2 inhibitors is conflicting.•The effect of SGLT2 inhibitors on cancer mortality is unknown.•Meta-analysis to evaluate cancer outcomes with SGLT2 inhibitor treatment in adults.•Pooled data of 116,365 participants showed no increse in risk of cancer outcomes.•TSA showed that the sample size was sufficient to avoid missing alternative results. Concerns regarding breast and bladder cancer risk with Sodium-glucose cotransporter-2 (SGLT2) inhibitors remain controversial and its effect on cancer mortality is unknown. We aim to evaluate the association between SGLT2 inhibitors and the risk of cancer outcomes. We searched PubMed, Embase and CENTRAL up to June 20th, 2022, for randomized controlled trials of SGLT2 inhibitors in adults, with a minimum follow-up of 48 weeks. Researchers extracted study-level data and assessed within-study risk of bias with the RoB 2.0 tool and quality of evidence with GRADE. We performed meta-analyses summarizing the relative risks (RRs) of cancer outcomes. Seventy-six trials encompassing 116,375 participants were selected. Overall risk of bias was low. SGLT2 inhibitors did not reduce/increase the overall risk of cancer (RR, 1.03; 95% confidence interval [CI], 0.96–1.10) and cancer mortality (RR, 0.99; 95% CI, 0.85–1.16). SGLT2 inhibitors likely result in little to no difference in the risk of breast (RR, 1.01; 95% CI 0.77–1.32) and bladder cancers (RR, 0.93; 95% CI 0.71–1.21). Trial sequential analysis provided evidence that the sample size was sufficient to avoid missing alternative results. SGLT2 inhibitors are not associated with an increased risk of cancer outcomes, providing reassuring data regarding previous safety concerns.