Vallo Volke1,2, Urmeli Katus3, Annika Johannson3, Karolin Toompere3, Keiu Heinla4, Kertu Rünkorg4,3, Anneli Uusküla3. 1. Department of Physiology, Institute of Biomedicine and Translational Medicine, Centre of excellence in Genomics and Translational Medicine, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia. vallo.volke@ut.ee. 2. Endocrinology Unit, Tartu University Hospital, 8 L. Puusepa Street, 51014, Tartu, Estonia. vallo.volke@ut.ee. 3. Department of Family Medicine and Public Health, University of Tartu, Tartu, Estonia. 4. Department of Physiology, Institute of Biomedicine and Translational Medicine, Centre of excellence in Genomics and Translational Medicine, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia.
Abstract
BACKGROUND: Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes. METHODS: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs. STUDY SELECTION: Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. OUTCOMES: The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia. SYNTHESIS OF RESULTS: Two reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780). RESULTS: Our final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules. CONCLUSION: Our meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile.
BACKGROUND: Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes. METHODS: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs. STUDY SELECTION: Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. OUTCOMES: The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia. SYNTHESIS OF RESULTS: Two reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780). RESULTS: Our final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules. CONCLUSION: Our meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile.
Authors: Paul Hartley; Yue Shentu; Patricia Betz-Schiff; Gregory T Golm; Christine McCrary Sisk; Samuel S Engel; R Ravi Shankar Journal: Drugs Aging Date: 2015-06 Impact factor: 3.923
Authors: Jonathan A C Sterne; Jelena Savović; Matthew J Page; Roy G Elbers; Natalie S Blencowe; Isabelle Boutron; Christopher J Cates; Hung-Yuan Cheng; Mark S Corbett; Sandra M Eldridge; Jonathan R Emberson; Miguel A Hernán; Sally Hopewell; Asbjørn Hróbjartsson; Daniela R Junqueira; Peter Jüni; Jamie J Kirkham; Toby Lasserson; Tianjing Li; Alexandra McAleenan; Barnaby C Reeves; Sasha Shepperd; Ian Shrier; Lesley A Stewart; Kate Tilling; Ian R White; Penny F Whiting; Julian P T Higgins Journal: BMJ Date: 2019-08-28
Authors: Steven E Kahn; Steven M Haffner; Mark A Heise; William H Herman; Rury R Holman; Nigel P Jones; Barbara G Kravitz; John M Lachin; M Colleen O'Neill; Bernard Zinman; Giancarlo Viberti Journal: N Engl J Med Date: 2006-12-04 Impact factor: 91.245
Authors: G Schernthaner; S Durán-Garcia; M Hanefeld; G Langslet; L Niskanen; C J Östgren; E Malvolti; E Hardy Journal: Diabetes Obes Metab Date: 2015-04-07 Impact factor: 6.577
Authors: Bo Ahrén; Susan L Johnson; Murray Stewart; Deborah T Cirkel; Fred Yang; Caroline Perry; Mark N Feinglos Journal: Diabetes Care Date: 2014-06-04 Impact factor: 19.112
Authors: M A Nauck; S Del Prato; S Durán-García; K Rohwedder; A M Langkilde; J Sugg; S J Parikh Journal: Diabetes Obes Metab Date: 2014-07-10 Impact factor: 6.577