BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a recent class of medication approved for the treatment of type 2 diabetes (T2D). Previous meta-analyses have quantified the benefits and harms of SGLT2Is; however, these analyses have been limited to specific outcomes and comparisons and included trials of short duration. We comprehensively reviewed the longer-term benefits and harms of SGLT2Is compared to placebo or other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov from inception to July 2019 for randomized controlled trials of minimum 52 weeks' duration that enrolled adults with T2D, compared an SGLT2I to either placebo or other anti-hyperglycemic medications, and reported at least one outcome of interest including cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events. We conducted random effects meta-analyses to provide summary estimates using weighted mean differences (MD) and pooled relative risks (RR). The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Fifty articles describing 39 trials (vs. placebo, n = 28; vs. other anti-hyperglycemic medication, n = 12; vs. both, n = 1) and 112,128 patients were included in our analyses. Compared to placebo, SGLT2Is reduced cardiovascular risk factors (e.g., hemoglobin A1c, MD - 0.55%, 95% CI - 0.62, - 0.49), macrovascular outcomes (e.g., hospitalization for heart failure, RR 0.70, 95% CI 0.62, 0.78), and mortality (RR 0.87, 95% CI 0.80, 0.94). Compared to other anti-hyperglycemic medications, SGLT2Is reduced cardiovascular risk factors, but insufficient data existed for other outcomes. About a fourfold increased risk of genital yeast infections for both genders was observed for comparisons vs. placebo and other anti-hyperglycemic medications. DISCUSSION: We found that SGLT2Is led to durable reductions in cardiovascular risk factors compared to both placebo and other anti-hyperglycemic medications. Reductions in macrovascular complications and mortality were only observed in comparisons with placebo, although trials comparing SGLT2Is vs. other anti-hyperglycemic medications were not designed to assess longer-term outcomes.
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a recent class of medication approved for the treatment of type 2 diabetes (T2D). Previous meta-analyses have quantified the benefits and harms of SGLT2Is; however, these analyses have been limited to specific outcomes and comparisons and included trials of short duration. We comprehensively reviewed the longer-term benefits and harms of SGLT2Is compared to placebo or other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov from inception to July 2019 for randomized controlled trials of minimum 52 weeks' duration that enrolled adults with T2D, compared an SGLT2I to either placebo or other anti-hyperglycemic medications, and reported at least one outcome of interest including cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events. We conducted random effects meta-analyses to provide summary estimates using weighted mean differences (MD) and pooled relative risks (RR). The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Fifty articles describing 39 trials (vs. placebo, n = 28; vs. other anti-hyperglycemic medication, n = 12; vs. both, n = 1) and 112,128 patients were included in our analyses. Compared to placebo, SGLT2Is reduced cardiovascular risk factors (e.g., hemoglobin A1c, MD - 0.55%, 95% CI - 0.62, - 0.49), macrovascular outcomes (e.g., hospitalization for heart failure, RR 0.70, 95% CI 0.62, 0.78), and mortality (RR 0.87, 95% CI 0.80, 0.94). Compared to other anti-hyperglycemic medications, SGLT2Is reduced cardiovascular risk factors, but insufficient data existed for other outcomes. About a fourfold increased risk of genital yeast infections for both genders was observed for comparisons vs. placebo and other anti-hyperglycemic medications. DISCUSSION: We found that SGLT2Is led to durable reductions in cardiovascular risk factors compared to both placebo and other anti-hyperglycemic medications. Reductions in macrovascular complications and mortality were only observed in comparisons with placebo, although trials comparing SGLT2Is vs. other anti-hyperglycemic medications were not designed to assess longer-term outcomes.
Authors: Jennifer R Donnan; Catherine A Grandy; Eugene Chibrikov; Carlo Marra PharmD; Kris Aubrey-Bassler; Karissa Johnston; Michelle Swab; Jenna Hache; Daniel Curnew; Hai Nguyen; John-Michael Gamble Journal: CMAJ Open Date: 2018-12-10
Authors: Bernard Zinman; Christoph Wanner; John M Lachin; David Fitchett; Erich Bluhmki; Stefan Hantel; Michaela Mattheus; Theresa Devins; Odd Erik Johansen; Hans J Woerle; Uli C Broedl; Silvio E Inzucchi Journal: N Engl J Med Date: 2015-09-17 Impact factor: 91.245
Authors: Brendon L Neuen; Tamara Young; Hiddo J L Heerspink; Bruce Neal; Vlado Perkovic; Laurent Billot; Kenneth W Mahaffey; David M Charytan; David C Wheeler; Clare Arnott; Severine Bompoint; Adeera Levin; Meg J Jardine Journal: Lancet Diabetes Endocrinol Date: 2019-09-05 Impact factor: 32.069
Authors: Hiddo J L Heerspink; Avraham Karasik; Marcus Thuresson; Cheli Melzer-Cohen; Gabriel Chodick; Kamlesh Khunti; John P H Wilding; Luis Alberto Garcia Rodriguez; Lucia Cea-Soriano; Shun Kohsaka; Antonio Nicolucci; Giuseppe Lucisano; Fang-Ju Lin; Chih-Yuan Wang; Eric Wittbrodt; Peter Fenici; Mikhail Kosiborod Journal: Lancet Diabetes Endocrinol Date: 2020-01 Impact factor: 32.069
Authors: Julian P T Higgins; Douglas G Altman; Peter C Gøtzsche; Peter Jüni; David Moher; Andrew D Oxman; Jelena Savovic; Kenneth F Schulz; Laura Weeks; Jonathan A C Sterne Journal: BMJ Date: 2011-10-18
Authors: David C Mohr; Libin Zhang; Julia C Prentice; Richard E Nelson; Donglin Li; Erin Pleasants; Paul R Conlin Journal: BMJ Open Diabetes Res Care Date: 2022-07