The effectiveness, safety and epidemiology of the use of acarbose in the treatment of patients with type II diabetes mellitus - A model of medicine-based evidence
N. Scorpiglione et al., The effectiveness, safety and epidemiology of the use of acarbose in the treatment of patients with type II diabetes mellitus - A model of medicine-based evidence, EUR J CL PH, 55(4), 1999, pp. 239-249
Objective: To assess the efficacy, safety and extent of perceived indicatio
ns of acarbose, a new anti diabetic agent, under routine clinical practice
conditions in an unselected Northern Italian population of type II diabetic
patients.
Method's: The study population was assigned to three different groups accor
ding to the physician's clinical judgement: group A (acarbose considered as
an elective treatment); group B (acarbose considered to be of uncertain be
nefit); group C (acarbose deemed not to be appropriate). Group B patients w
ere randomized either to continue their standard treatment or to add acarbo
se to it, Patients with type II diabetes mellitus were recruited from 17 di
abetes outpatient clinics from one Italian region (Lombardy). A total of 10
27 patients were recruited (group A: 283; group C: 494; group B: 250, of wh
om 124 were randomly assigned to standard treatment + acarbose and 126 to s
tandard treatment alone). Acarbose was administered for 1 year at a median
dose of 100 mg 3 times daily. Drug efficacy was evaluated in terms of mean
HbA1c, pre- and post-prandial glycaemic values. Additional endpoints were t
he proportion of patients with HbA1c levels below 8% at the end of the stud
y period and the proportion of subjects who needed a modification in the st
andard treatment. The safety and tolerability profiles of the drug were als
o investigated. Data on HbA1c, fasting and post-prandial blood glucose leve
ls were analysed over time using repeated-measures analysis [Generalized Es
timating Equation (GEE) models].
Results: The analysis of Group B showed that, after treatment for 1 year, t
he mean reduction in HbA1c levels in the acarbose group with respect to the
control group was 0.30% (95% confidence limits -0.60 +0.02, P = 0.07), whi
le the mean reduction in post-prandial glycaemia was 17 mg . dl(-1) (95% c.
l, -33.5 -0.8; P = 0.04). No difference resulted for fasting blood glucose
levels. When looking at the baseline HbA1c levels, it emerged that the mean
benefit associated with the use of acarbose was 0.14% (95% c.l. -0.6 +0.28
; P = 0.5) in patients with HbA1c levels below 8%, 0.28% (95% c.l. -0.6 +0.
05; P = 0.09) in those with values between 8% and 9.9% and 0.65% (95% c.l.
-1.36 + 0.06; P = 0.07) in those with values greater than or equal to 10%.
Only patients treated with diet +/- oral anti-diabetic agents (OAA) benefit
ed from acarbose treatment (mean benefit = 0.37%, 95% c.l. -0.65 -0.08), wh
ile no effect was shown for insulin-treated subjects. The proportion of pat
ients with HbA1c below 8% increased from 31% to 44% in the acarbose group a
nd from 40% to 45% in the control group (absolute difference between baseli
ne and end-of-study values = 8.0% in favour of acarbose-treated patients; P
= 0.058). Patients treated with acarbose were significantly more likely to
undergo a dose reduction in concomitant diabetic treatments compared with
the control group; they were also less likely to require an increase in the
dose of standard treatment and to start insulin during the study period. O
ne third of the patients could not assume the drug for the whole study peri
od, mainly due to gastrointestinal side-effects.
Conclusions: The design adopted in this study allowed an integrated evaluat
ion of the overall effectiveness of acarbose in clinical practice. The bene
fits of the drug in an unselected population of non-insulin-dependent diabe
tes mellitus (NIDDM) patients are significant but of marginal clinical rele
vance. Only a better definition of the subgroups of patients who are more l
ikely to benefit from long-term treatment, particularly through possible po
stponement of secondary OAA failure, will allow a reliable definition of th
e cost-effectiveness of this complementary component of anti-diabetic strat
egy.