Effect of targeting normal fasting glucose levels with basal insulin glargine on glycaemic variability and risk of hypoglycaemia: a randomized, controlled study in patients with early Type 2 diabetes


  • NCT00069784, ClinicalTrials.gov.

Markolf Hanefeld, GWT-TUD GmbH, Center for Clinical Studies, Fiedlerstraße 34, 01307 Dresden, Germany. E-mail: hanefeld@gwtonline-zks.de


Diabet. Med. 27, 175–180 (2010)


Aims  The purpose of this sub-study of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial was to determine efficacy and safety of targeting normal fasting plasma glucose (FPG) levels in patients with early Type 2 diabetes treated with insulin glargine in comparison with standard care.

Methods  Participants were randomly allocated to insulin or standard care. Insulin was titrated to reach FPG ≤ 5.3 mmol/l. Two years after randomization in a small subset (43 glargine, 32 standard care), continuous glucose measurement (CGMS® System Gold™), including a test meal, was performed. Sixteen volunteers with normal oral glucose tolerance test (OGTT) served as control subjects. Objectives were glycaemic variability, standard deviation (sd), mean amplitude of glucose excursion (MAGE) with postprandial glucose excursion after the test meal, time spent < 3.0 mmol/l interstitial glucose.

Results  Participants allocated to insulin and standard care had FPG levels of 5.3 and 6.1 mmol/l (P = 0.019) and glycated haemoglobin (HbA1c) 5.7% and 5.9%, respectively (P < 0.025). Time (min/24 h) spent at low glucose levels was not significantly different between groups (30.6 ± 83.8 min control subjects, 33.7 ± 75.1 min insulin, 10.6 ± 50.6 min standard care). Standard deviation and MAGE were similar for glargine and standard care, but significantly higher than in control subjects. If FPG was < 5.3 mmol/l, the postprandial glucose excursion was in the range seen in control subjects.

Conclusions  Treatment to target of FPG < 5.3 mmol/l with insulin glargine was not associated with significantly increased risk of hypoglycaemia. Strict control of FPG with insulin glargine was effective to control postprandial glucose excursion, but had no significant effect on sd and MAGE.