Rr. Holman et al., A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (UK Prospective Diabetes Study 44), DIABET CARE, 22(6), 1999, pp. 960-964
OBJECTIVE - To determine the degree to which a-glucosidase inhibitors, with
their unique mode of action primarily reducing postprandial hyperglycemia,
offer an additional therapeutic approach in the long-term treatment of typ
e 2 diabetes.
RESEARCH DESIGN AND METHODS - We studied 1,946 patients (63% men) who were
previously enrolled in the U.K. Prospective Diabetes Study (UKPDS). The pat
ients were randomized to acarbose (n = 973), titrating to a maximum dose of
100 mg three times per day, or to matching placebo (n = 973). Mean +/- SD
age was 59 +/- 9 years, body weight 84 +/- 17 kg, diabetes duration 7.6 +/-
2.9 years, median (interquartile range) HbA(1c) 7.9% (6.7-9.5), and fastin
g plasma glucose (FPG) 8.7 mmol/l (6.8-11.1). Fourteen percent of patients
were treated with diet alone, 52% with monotherapy, and 34% with combined t
herapy. Patients were monitored in UKPDS clinics every 4 months for 3 years
. The main outcome measures were HbA(1c), FPG, body weight, compliance with
study medication, incidence of side effects, and frequency of major clinic
al events.
RESULTS - At 3 years, a lower proportion of patients were taking acarbose c
ompared with placebo (39 vs. 58%, P < 0.0001), the main reasons for noncomp
liance being flatulence (30 vs. 12%, P < 0.0001) and diarrhea (16 vs. 8%, P
< 0.05). Analysis by intention to treat showed that patients allocated to
acarbose, compared with placebo, had 0.2% significantly lower median HbA(1c
) at 3 years (P < 0.001). In patients remaining on their allocated therapy,
the HbA(1c) difference at 3 years (309 acarbose, 470 placebo) was 0.5% low
er median HbA(1c) (8.1 vs. 8.6%, P < 0.0001). Acarbose appeared to be equal
ly efficacious when given in addition to diet alone; in addition to monothe
rapy with a sulfonylurea, metformin, or insulin; or in combination with mor
e complex treatment regimens. No significant differences were seen in FPG,
body weight, incidence of hypoglycemia, or frequency of major clinical even
ts.
CONCLUSIONS - Acarbose significantly improved glycemic control over 3 years
in patients with established type 2 diabetes, irrespective of concomitant
therapy for diabetes. Careful titration of acarbose is needed in view of th
e increased noncompliance rate seen secondary to the known side effects.