Insulin therapy in type 2 diabetes: what is the evidence?
OBJECTIVE
To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitus


METHODS
A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements.


RESULTS
The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long-acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long-acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long-acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal-bolus regimen seems not possible. Some studies showed that rapid-acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin.


CONCLUSIONS
A once-daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years.
van Avendonk
Mariëlle J P
MJ
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. m.j.p.vanavendonk@umcutrecht.nl
Rutten
Guy E H M
GE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000150:complications; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin