Treatment with diet alone, insulin, sulfonylurea, or
metformin is known to improve glycemia in patients with type 2 diabetes
mellitus, but which treatment most frequently attains target fasting
plasma glucose (FPG) concentration of less than 7.8 mmol/L (140 mg/dL)
or glycosylated hemoglobin A1c(HbA1c) below
7% is unknown.
To assess how often each therapy can achieve the
glycemic control target levels set by the American Diabetes
Randomized controlled trial conducted between 1977 and
1997. Patients were recruited between 1977 and 1991 and were followed
up every 3 months for 3, 6, and 9 years after enrollment.
Outpatient diabetes clinics in 15 UK hospitals.
A total of 4075 patients newly diagnosed as having type 2
diabetes ranged in age between 25 and 65 years and had a median
(interquartile range) FPG concentration of 11.5 (9.0-14.4) mmol/L [207
(162-259) mg/dL], HbA1c levels of 9.1% (7.5%-10.7%),
and a mean (SD) body mass index of 29 (6) kg/m2.
After 3 months on a low-fat,
high-carbohydrate, high-fiber diet, patients were randomized to therapy
with diet alone, insulin, sulfonylurea, or metformin.
Main Outcome Measures
Fasting plasma glucose and HbA1c
levels, and the proportion of patients who achieved target levels below
7% HbA1c or less than 7.8 mmol/L (140 mg/dL) FPG at 3, 6,
or 9 years following diagnosis.
The proportion of patients who maintained target
glycemic levels declined markedly over 9 years of follow-up. After 9
years of monotherapy with diet, insulin, or sulfonylurea, 8%, 42%,
and 24%, respectively, achieved FPG levels of less than 7.8 mmol/L
(140 mg/dL) and 9%, 28%, and 24% achieved HbA1c levels
below 7%. In obese patients randomized to metformin, 18% attained FPG
levels of less than 7.8 mmol/L (140 mg/dL) and 13% attained
HbA1c levels below 7%. Patients less likely to achieve
target levels were younger, more obese, or more hyperglycemic than
Each therapeutic agent, as monotherapy, increased 2- to
3-fold the proportion of patients who attained HbA1c
below 7% compared with diet alone. However, the progressive
deterioration of diabetes control was such that after 3 years
approximately 50% of patients could attain this goal with monotherapy,
and by 9 years this declined to approximately 25%. The majority of
patients need multiple therapies to attain these glycemic target levels
in the longer term.