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

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.