Huilin Tang1,2,3, Qi Dai4, Weilong Shi1, Suodi Zhai1, Yiqing Song5,6, Jiali Han7,8,9. 1. Department of Pharmacy, Peking University Third Hospital, Beijing, People's Republic of China. 2. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, 1050 Wishard Blvd, Indianapolis, IN, 46202, USA. 3. Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA. 4. Department of Medicine, School of Medicine, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, USA. 5. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, 1050 Wishard Blvd, Indianapolis, IN, 46202, USA. yiqsong@iu.edu. 6. Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA. yiqsong@iu.edu. 7. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, 1050 Wishard Blvd, Indianapolis, IN, 46202, USA. jialhan@iu.edu. 8. Center for Pharmacoepidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA. jialhan@iu.edu. 9. Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA. jialhan@iu.edu.
Abstract
AIMS/HYPOTHESIS: The association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes. METHODS: We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs. RESULTS: In total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61 weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]). CONCLUSIONS/ INTERPRETATION: Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.
AIMS/HYPOTHESIS: The association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of cancer in individuals with type 2 diabetes remains uncertain. This study aimed to evaluate the risk of cancer associated with SGLT2 inhibitor treatment of type 2 diabetes. METHODS: We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to 15 February 2017 to identify eligible randomised controlled trials (RCTs) that report cancer events in individuals with type 2 diabetes treated with SGLT2 inhibitors for at least 24 weeks. We performed pairwise and network meta-analyses as well as a cumulative meta-analysis to calculate ORs and 95% CIs. RESULTS: In total, 580 incidences of cancer among 34,569 individuals were identified from 46 independent RCTs with a mean trial duration of 61 weeks. When compared with comparators (placebo or other active glucose-lowering treatments), SGLT2 inhibitors were not significantly associated with an increased risk of overall cancer (OR 1.14 [95% CI 0.96, 1.36]). For pre-specified cancer types, the risk of bladder cancer might be increased with SGLT2 inhibitors (OR 3.87 [95% CI 1.48, 10.08]), especially empagliflozin (OR 4.49 [95% CI 1.21, 16.73]). Interestingly, canagliflozin might be protective against gastrointestinal cancers (OR 0.15 [95% CI 0.04, 0.60]). CONCLUSIONS/ INTERPRETATION: Current evidence from short-term RCTs did not indicate a significantly increased risk of overall cancer among individuals with type 2 diabetes using SGLT2 inhibitors. Given the short-term trial durations and uncertainty of evidence, future long-term prospective studies and post-marketing surveillance studies are warranted.
Authors: Silvio E Inzucchi; Richard M Bergenstal; John B Buse; Michaela Diamant; Ele Ferrannini; Michael Nauck; Anne L Peters; Apostolos Tsapas; Richard Wender; David R Matthews Journal: Diabetes Care Date: 2015-01 Impact factor: 19.112
Authors: F J Lavalle-González; A Januszewicz; J Davidson; C Tong; R Qiu; W Canovatchel; G Meininger Journal: Diabetologia Date: 2013-09-13 Impact factor: 10.122