Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus - Progressive requirement for multiple therapies (UKPDS 49)
Rc. Turner et al., Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus - Progressive requirement for multiple therapies (UKPDS 49), J AM MED A, 281(21), 1999, pp. 2005-2012
Citations number
30
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Context Treatment with diet alone, insulin, sulfonylurea, or metformin is k
nown to improve glycemia in patients with type 2 diabetes mellitus, but whi
ch treatment most frequently attains target fasting plasma glucose (FPG) co
ncentration of less than 7.8 mmol/L (140 mg/dL) or glycosylated hemoglobin
A(1c) (HbA(1c)) below 7% is unknown.
Objective To assess how often each therapy can achieve the glycemic control
target levels set by the American Diabetes Association.
Design Randomized controlled trial conducted between 1977 and 1997. Patient
s were recruited between 1977 and 1991 and were followed up every 3 months
for 3, 6, and 9 years after enrollment.
Setting Outpatient diabetes clinics in 15 UK hospitals.
Patients 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 rang
e) FPG concentration of 11.5 (9.0-14.4) mmol/L [207 (162-259) mg/dL], HbA(1
c) levels of 9.1% (7.5%-10.7%), and a mean (SD) body mass index of 29 (6) k
g/m(2).
Interventions After 3 months on a low-fat, high-carbohydrate, high-fiber di
et, patients were randomized to therapy with diet alone, insulin, sulfonylu
rea, or metformin.
Main Outcome Measures Fasting plasma glucose and HbA(1c) levels, and the pr
oportion of patients who achieved target levels below 7% HbA(1c) or less th
an 7.8 mmol/L (140 mg/dL) FPG at 3, 6, or 9 years following diagnosis.
Results The proportion of patients who maintained target glycemic levels de
clined markedly over 9 years of follow-up. After 9 years of monotherapy wit
h 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% achieve
d HbA(1c) levels below 7%. In obese patients randomized to metformin, 18% a
ttained FPG levels of less than 7.8 mmol/L (140 mg/dL) and 13% attained HbA
(1c) levels below 7%. Patients less likely to achieve target levels were yo
unger, more obese, or more hyperglycemic than other patients.
Conclusions Each therapeutic agent, as monotherapy, increased 2- to 3-fold
the proportion of patients who attained HbA(1c) 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 wi
th monotherapy, and by 9 years this declined to approximately 25%. The majo
rity of patients need multiple therapies to attain these glycemic target le
vels in the longer term.