title: Composite endpoints in trials of type-2 diabetes.
abstract: Composite endpoints (CEPs) are being used more frequently as outcomes for trials of drugs in type-2 diabetes. We reviewed the literature to determine how CEPs have been used to date in trials of drugs for type-2 diabetes. A systematic search was undertaken on Medline, Embase and Cochrane databases and Clinicaltrials.gov for randomized controlled trials of currently marketed agents including SGLT-2 inhibitors (dapagliflozin), GLP-1 agonists (exenatide, liraglutide) and DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin and vildagliptin). CEPs used were identified as well as numbers and percentages of patients achieving each. Thirty-six studies were identified that reported results on ≥1 CEP; 15 different CEPs were reported (7 with 2 components, 8 with 3 components). All CEPs addressed goals recommended by the American Diabetes Association (ADA). All included HbA1c<7%; other endpoints measured weight, blood pressure and hypoglycaemic events. Results were obtained for CEPs from 6 months to 2 years. Rates of achieving CEPs decreased with increasing numbers of components and outcomes assessed. CEPs are becoming used as indicators of clinical outcomes in type-2 diabetes trials, but are still not common. More research is required to identify optimal CEPs. Standardization of outcomes and their reporting is needed.
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
authors.forename: T R
authors.initials: TR
authors.lastname: Einarson
authors.forename: M
authors.initials: M
authors.lastname: Garg
authors.forename: V
authors.initials: V
authors.lastname: Kaur
authors.forename: M E H
authors.initials: ME
authors.lastname: Hemels
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D052216:Glucagon-Like Peptide 1
keywords: HbA1c; clinical trials; composite endpoints; type-2 diabetes