title: Treat-to-target trials: uses, interpretation and review of concepts.
abstract: Treat-to-target trial designs compare investigational insulins with a standard insulin. Treat-to-target trials force-titrate insulin dosages to achieve a prespecified treatment goal. With comparable glycaemic control, comparisons of safety endpoints such as hypoglycaemia can be made to establish the risk-benefit profile of the new insulin. Glargine versus NPH showed comparable A1C reductions; however, A1C <7% without associated nocturnal hypoglycaemia was reached in more patients on glargine and overall hypoglycaemia was lower. Detemir versus glargine showed non-inferiority between the groups; however, with less weight gain and more injection site reactions with detemir. Detemir/aspart versus glargine/aspart showed non-inferiority between the treatments, however, with less weight gain in the detemir group but comparable risk of hypoglycaemia. Degludec in combination with aspart versus glargine/aspart showed comparable A1C reductions. However, degludec-treated patients had less overall hypoglycaemia and less nocturnal hypoglycaemia. Because insulin titrations are guided by goal attainment with each treatment, treat-to-target trials enable clinicians to determine differences in non-glycaemic treatment effects, such as rates of hypoglycaemia and weight gain, at the same level of glycaemic control.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Garber
mesh_terms: D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D061267:Insulin Aspart / Q000627:therapeutic use; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000627:therapeutic use; D008297:Male; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C571886:insulin degludec
keywords: insulin aspart; insulin degludec; insulin detemir; insulin glargine; neutral protamine Hagedorn (NPH); treat-to-target trials; type 2 diabetes