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© 2003 by the American Diabetes Association, Inc.
Emerging Treatments and Technologies |
The Treat-to-Target Trial
Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients
1 Oregon Health and Science University, Portland, Oregon
2 Dallas Diabetes and Endocrine Center, Dallas, Texas
3 University of Rochester Medical Center, Rochester, New York
Address correspondence and reprint requests to Matthew C. Riddle, MD, Oregon Health and Science University, Section of Diabetes L-345, 3181 S.W. Sam Jackson, Portland, OR 97201. E-mail: riddlem{at}ohsu.edu
OBJECTIVE—To compare the abilities and associated hypoglycemia risks of insulin glargine and human NPH insulin added to oral therapy of type 2 diabetes to achieve 7% HbA1c.
RESEARCH DESIGN AND METHODS—In a randomized, open-label, parallel, 24-week multicenter trial, 756 overweight men and women with inadequate glycemic control (HbA1c >7.5%) on one or two oral agents continued prestudy oral agents and received bedtime glargine or NPH once daily, titrated using a simple algorithm seeking a target fasting plasma glucose (FPG) 
100 mg/dl (5.5 mmol/l). Outcome measures were FPG, HbA1c, hypoglycemia, and percentage of patients reaching HbA1c 7% without documented nocturnal hypoglycemia.
RESULTS—Mean FPG at end point was similar with glargine and NPH (117 vs. 120 mg/dl [6.5 vs. 6.7 mmol/l]), as was HbA1c (6.96 vs. 6.97%). A majority of patients (
60%) attained HbA1c 7% with each insulin type. However, nearly 25% more patients attained this without documented nocturnal hypoglycemia (72 mg/dl [4.0 mmol/l]) with glargine (33.2 vs. 26.7%, P < 0.05). Moreover, rates of other categories of symptomatic hypoglycemia were 21–48% lower with glargine.
CONCLUSIONS—Systematically titrating bedtime basal insulin added to oral therapy can safely achieve 7% HbA1c in a majority of overweight patients with type 2 diabetes with HbA1c between 7.5 and 10.0% on oral agents alone. In doing this, glargine causes significantly less nocturnal hypoglycemia than NPH, thus reducing a leading barrier to initiating insulin. This simple regimen may facilitate earlier and effective insulin use in routine medical practice, improving achievement of recommended standards of diabetes care.
Abbreviations: FPG, fasting plasma glucose • ITT, intent to treat • UKPDS, U.K. Prospective Diabetes Study
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