Treat-to-target trials: uses, interpretation and review of concepts

Diabetes Obes Metab. 2014 Mar;16(3):193-205. doi: 10.1111/dom.12129. Epub 2013 Jun 14.


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.

Keywords: insulin aspart; insulin degludec; insulin detemir; insulin glargine; neutral protamine Hagedorn (NPH); treat-to-target trials; type 2 diabetes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A / drug effects*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / chemically induced*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Insulin / blood
  • Insulin / therapeutic use*
  • Insulin Aspart / therapeutic use
  • Insulin Detemir
  • Insulin Glargine
  • Insulin, Long-Acting / therapeutic use
  • Male
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Treatment Outcome


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • hemoglobin A1c protein, human
  • Insulin Glargine
  • Insulin Detemir
  • insulin degludec
  • Insulin Aspart