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Predictors of Persistence of Use of the Novel Antidiabetic Agent Acarbose
Vanessa S. Catalan, PhD;
Julie A. Couture, MD;
Jacques LeLorier, MD, PhD
Arch Intern Med. 2001;161:1106-1112.
ABSTRACT
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Background A carbose is the first of a new class of antidiabetic agents, the  -glucosidase
inhibitors.This study characterizes and identifies predictors of persistence
of use of acarbose.
Methods Medical, pharmaceutical, and demographic records were extracted for
2 cohorts of patients (social assistance recipients and seniors) from the
databases of Quebec's provincial health plan. Patients were eligible for inclusion
if they had received their first dispensation of acarbose between August 1,
1996, and December 31, 1997. The observation period included at least 1 year
before the first dispensation and a minimum of 4 months after.
Results New users of acarbose included 216 social assistance recipients and
677 seniors who were followed up for 82 914 and 270 041 person-days,
respectively. Median persistence with acarbose treatment was 83 days (95%
confidence interval, 75-105 days) for social assistance recipients and 105
days (95% confidence interval, 90-119 days) for seniors. In both cohorts,
treatment by an endocrinologist vs another physician predicted longer treatment
persistence. In the seniors cohort, additional determinants of (earlier) treatment
discontinuation included a higher initial daily dose, previous treatment with
insulin, and consultation with a gastroenterologist after treatment initiation.
Conclusions New users of acarbose showed low persistence in 2 cohorts of beneficiaries
of Quebec's provincial health plan. Prescribing specialist was an important
predictor of persistence in seniors and the socially assisted. The importance
of 4 additional factors in seniors only led to hypotheses concerning population
differences in treatment expectations and in the occurrence and tolerance
of adverse effects.
INTRODUCTION
ACARBOSE IN THE first of a new class of oral antidiabetic
agents (the -glucosidase inhibitors). The clinical practice guidelines
of the Canadian Diabetes Association1 recommend
acarbose for the treatment of type 2 diabetes mellitus as monotherapy (in
addition to dietary modification) or as add-on therapy for patients who are
not well controlled with other oral antidiabetic agents (metformin and sulfonylureas)
or insulin. Gastrointestinal adverse effects are noted as a possible limiting
factor.1 Although the efficacy and safety of
acarbose in hyperglycemic control have been well demonstrated,2-4
approximately 50% or more of acarbose-treated participants in recent clinical
trials5-9
reported adverse gastrointestinal effects. Such effects arise by virtue of
the mechanism of action of acarbose, whereby the absorption of carbohydrates
from the intestine is delayed,10 providing
a substrate for fermentation by colonic flora.11
Although these effects are not serious and are known to diminish over time,9 patients in general clinical practice may not be adequately
informed of this fact or as motivated as trial participants to persist with
the therapy and hence may prematurely discontinue use of the agent. In 4 recent
randomized clinical trials5-7,9
on the use of acarbose as a first-line antidiabetic agent, the proportion
of randomized participants who did not complete the trials varied from 2%
to 29% (mean [SD], 14.8% [11.0%]). In the recent United Kingdom Prospective
Diabetes Study,4 in which preexisting therapies
of participants included diet alone (14%), monotherapy (52%), and combination
therapy (34%), 58% of participants assigned to the acarbose group (vs 39%
assigned to the placebo group) discontinued treatment after 3 years, with
the significantly lower compliance rate for the acarbose group being primarily
related to the higher proportion of patients reporting flatulence and diarrhea.
However, drug discontinuation is typically substantially higher in primary
care settings than in randomized clinical trials.12
The objective of the present study was to characterize the persistence
of use of acarbose among new (first-time) users of the drug in 2 cohorts of
beneficiaries of Quebec's provincial health plan. This characterization included
the quantification of persistence (as duration of treatment) and the identification
of its determinants. Such information will assist clinicians in appropriately
selecting and educating acarbose recipients to ensure maximal benefit from
using the drug.
PATIENTS AND METHODS
SOURCE OF DATA
The Régie de l'Assurance Maladie du Québec (RAMQ) is the
provincial health insurance plan for the province of Quebec. The RAMQ provides
drug and medical services coverage for persons receiving social assistance
("welfare") and for all persons older than 65 years. All claims data are captured
by the RAMQ administrative database and coded to preserve patient and physician
anonymity before their release for research purposes. The accuracy and comprehensiveness
of the RAMQ pharmaceutical data have been validated by Tamblyn et al.13
COHORT DEFINITION
From the RAMQ database, we retrieved demographic information and all
medical services and pharmaceutical records pertaining to the study period
July 1, 1995, through April 30, 1998, for all beneficiaries (including social
assistance recipients [SARs] and seniors) who had received at least 1 acarbose
dispensation between July 1, 1996 (the date on which acarbose was included
by the RAMQ as a reimbursable medication), and April 30, 1998. Patients remained
eligible for inclusion in the study if they had received their first (index)
acarbose dispensation during the baseline period (August 1, 1996, to December
31, 1997) and remained alive for at least 4 months after the index acarbose
dispensation (all patients met this criterion). Two mutually exclusive cohorts
of new users of acarbose were then defined by age restriction: (1) the SAR
cohort included beneficiaries of the revenue security program aged 21 to 64
years at their index (acarbose) dispensation and (2) the seniors cohort included
patients 66 years or older at their index dispensation.
The observation period for each cohort member included an antecedent
period, which extended from July 1, 1995, to the individual's index acarbose
dispensation date; an index period, which corresponded to the duration of
the individual's index dispensation; and a follow-up period, which extended
from the start of the individual's index dispensation to April 30, 1998.
OUTCOME DEFINITIONS
Two outcome variables were analyzed: (1) the frequency of renewal of
the first (index) acarbose dispensation (a dichotomous variable) and (2) the
persistence with acarbose treatment in days from the date of the index dispensation
(a continuous variable). We determined the frequency of renewal of the first
acarbose dispensation in 2 ways: (1) the proportion of those in each cohort
who ever renewed their initial (index) dispensation for acarbose by the end
of follow-up (April 30, 1998) regardless of any gap between the end of the
first dispensation and the beginning of the renewal and (2) the proportion
in each cohort who renewed their initial acarbose dispensation during the
study and within the permissible period (gap) between the prescribed end of
the first dispensation and the date of the next dispensation. The permissible
gap after the first dispensation was defined as half the duration of the index
dispensation or 7 days, whichever was longer.
Persistence with (duration of) acarbose treatment was defined as the
number of days from the date of the start of the index dispensation (index
date) to the time of first failure to continue renewals of acarbose with the
permissible gap between dispensations. As previously, the permissible gap
between the end date of a given acarbose dispensation and the date of renewal
was defined as half the duration of the given acarbose dispensation or 7 days,
whichever was greater. This definition of persistence corresponds to the duration
of treatment during which compliance (proportion of pills dispensed that would
have been consumed if taken as directed until the renewal date) remained greater
than 66%; patients were considered to have effectively discontinued treatment
at the point at which compliance dropped to less than 66%. The total duration
of treatment included the permissible gap after the final dispensation completed
during the study; for patients still being treated at the end of the study,
the duration of treatment was censored at that date.
STATISTICAL ANALYSIS
Predictors of persistence with acarbose treatment that were suspected
a priori from among the indicators available within the administrative databases
of RAMQ included age at index date, sex, region of habitation, type of medical
specialist who prescribed the index acarbose dispensation, consultation with
a gastroenterologist before or after the index dispensation (as an indicator
of gastrointestinal susceptibility or adverse effects, respectively), other
diabetic agents dispensed to the patient in the year before the first acarbose
dispensation, initial mean daily dose of acarbose (in milligrams per day),
and other medications whose duration of dispensation included the index date.
A chronic disease score (CDS) (a global index of illness) at the index dispensation
was computed according to a method14 that weights
concomitant medications according to their usual indications.
The CDS was calculated by assigning scores (0-5) to classes of drugs
according to the severity of the disease for which they were prescribed; the
CDS was equal to the sum of scores for drugs dispensed to patients during
the index acarbose dispensation.
For each of the 2 alternative definitions of renewal of the first dispensation
and for each of the suspected predictors, crude stratified analyses were conducted
by computing the frequency of renewal within strata defined by categories
of the predictor. The occurrence and direction of a change in the mean daily
dose ( 25 mg) of acarbose after the index dispensation were also investigated
in those who ever had a renewal. Ever-renewers were also subcategorized as
either compliant or noncompliant renewers according to whether the first renewal
occurred within the permissible gap.
Survival functions describing persistence of acarbose treatment were
computed using the SAS life test procedure (SAS Institute Inc, Cary, NC).
Patients who continued being treated at the end of follow-up were censored
at that time and contributed information to the survival curve (as cumulative
probability of "survival" on treatment) until that date only.
Multivariate analyses to identify independent determinants of acarbose
renewal and treatment persistence were conducted using multiple logistic regression
and the Cox proportional hazards model, respectively. The latter time-to-failure
analysis also controlled for the duration of the index dispensation. Potential
modifiers of the assumed multiplicative relation among model covariates were
also investigated. These evaluated the potential for (1) variable predictivity
of the type of prescribing specialist (endocrinologist vs internist or others)
depending on the initial acarbose dosage, antecedent use (indicated by a filled
prescription) of insulin or other oral antidiabetic agents, and CDS and (2)
variable predictivity of consultation with a gastroenterologist after the
index prescription depending on the initial daily dose of acarbose, sex, age,
prescribing specialist, and habitation outside metropolitan Montreal, Quebec.
Analyses were conducted separately within the 2 cohorts until a best model
was selected in each. Interactions among covariates in the best first-order
multivariate model were also tested. A liberal = .2 was used for the
testing of interaction terms. The final analyses for each cohort included
all variables observed to be important independent determinants of the respective
outcome (odds of renewal in the case of multiple logistic regression and persistence
of treatment in the Cox regression) in either cohort.
RESULTS
FREQUENCY OF FIRST USE
Analyses of the RAMQ databases indicated that 216 Quebecois SARs aged
21 to 64 years received a first dispensation of acarbose during the baseline
period. According to statistics provided by the Régie Régionale
de la Santé et des Services Sociaux du Montréal-Centre, Montreal
(Costas Kapetanakis, MSc, written communications, January 27, 1999), the total
number of Quebec residents aged 20 to 65 years who were SARs as of December
31, 1997 (the end of the baseline period), was 491 559. According to
the most recent (1991) Quebec survey data (Costas Kapetanakis, MSc, written
communications, January 27, 1999), approximately 2.5% of the Quebec general
population aged 20 to 64 years are diabetic (including types 1 and 2). During
the defined baseline period, first users of acarbose thus constituted approximately
1.8% of prevalent diabetic SARs in Quebec.
A total of 677 Quebec residents 66 years or older received an initial
dispensation of acarbose during the baseline period. At the census date closest
to this period (July 1997), the Quebec population 65 years and older numbered
884 875. Quebec survey data (Costas Kapetanakis, MSc, written communications,
January 27, 1999) indicate a prevalence of diabetes among those 65 years and
older of 10.3%. Acarbose was thus first prescribed to approximately 0.7% of
prevalent diabetics older than 65 years in Quebec during the defined baseline
period.
The 2 cohorts of new users of acarbose (216 SARs and 677 seniors) were
followed up for 82 593 (SARs) and 268 318 (seniors) person-days
after their index dispensation. Median follow-up was 392 days (range, 128-637
days) for SARs and 412 days (range, 127-637 days) for seniors.
BASELINE CHARACTERISTICS
Characteristics of new users of acarbose at the index dispensation are
summarized in Table 1. Mean age
at the date of the index dispensation was 51 years for SARs and 72 years for
seniors. In the former cohort, only 7% were 35 years or younger at the index
date. Sixty-two percent of the SAR cohort and 55% of the seniors cohort were
women. The regional distribution was similar in the 2 cohorts, with a third
of the members living in metropolitan Montreal. None of the patients had consulted
a gastroenterologist in the year before the index date. Comorbidity, as indicated
by the CDS, was only slightly higher in the seniors than in the SAR cohort.
Most first acarbose dispensations were prescribed by endocrinologists (56%
of SARs and 62% of seniors) or internists (36% of SARs and 29% of seniors),
with only a small proportion being prescribed by general practitioners or
other physicians (8% of SARs and 9% of seniors). The dosage of acarbose did
not differ between the 2 cohorts; 94% of index dispensations were for 50-mg
units, with the remainder in 100-mg units; the median initial daily dose was
100 mg. During the study period, the recommended initial daily dose was 75
mg.15
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Table 1. Characteristics of New Users of Acarbose at the Index Dispensation*
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With respect to concomitant antidiabetic agents, a slightly greater
proportion of SARs (49%) than seniors (41%) were prescribed acarbose alone
at the index date; a slightly lower proportion of SARs (38%) than seniors
(49%) were prescribed another oral agent (without insulin) concomitantly with
acarbose. At the time of the study, sulfonylureas were the only other oral
antidiabetic agents approved as concomitant agents15
and were, in fact, the only other oral antidiabetic agents codispensed to
study patients. Ten percent of SARs and 9% of seniors were prescribed only
insulin concomitantly with acarbose; 3% of SARs and 1% of seniors were coprescribed
acarbose with a sulfonylurea and insulin. The coprescription of insulin and
sulfonylureas was formally approved in 1999.16
USE OF OTHER ANTIDIABETIC AGENTS
Most patients (57% in the 2 cohorts combined) were initially prescribed
acarbose in combination with another agent, and coprescribed antidiabetic
agents were generally those that patients had used before acarbose. Acarbose
is therefore generally being used as recommended,1
ie, as an add-on to previous therapy, whether that be diet alone (first line),
other oral antidiabetic agents (second line), insulin alone (third line),
or insulin plus other antidiabetic oral agents (fourth line).
From the perspective of antecedent use of other antidiabetic agents,
among SARs, the largest group of new users were prescribed acarbose as a first-line
agent (44%), with successively smaller proportions being prescribed acarbose
as a second- (39%), third- (9%), or fourth- (7%) line agent. Among seniors,
however, most new users were prescribed acarbose as a second-line agent (52%),
with successively smaller proportions being prescribed acarbose as a first-
(35%), third- (9%), or fourth- (4%) line agent.
FREQUENCY OF FIRST RENEWAL
Seventy-three percent of SARs and 80% of seniors ever renewed their
first dispensation of acarbose; among these ever-renewers, similar proportions
in each cohort (83% of SARs and 81% of seniors) were what we termed "compliant
renewers." Expressed as a proportion of all new users in the defined cohorts,
60% of SARs and 65% of seniors renewed their first dispensation of acarbose
within the permissible gap.
PERSISTENCE WITH ACARBOSE TREATMENT
Survival curves depicting persistence with acarbose treatment are given
in Figure 1. In both cohorts, a
sharp drop (corresponding to 27% of SARs and 22% of seniors) in the number
of patients persisting with treatment was observed 45 days after the index
date, which corresponds to the end of the permissible renewal interval after
a 30-day dispensation; 30 days is in fact the most frequent duration of all
prescriptions among seniors in Quebec.13 The
survival curves for the 2 cohorts remained roughly parallel in their descent
from 45 days after the index dispensation. Only a small proportion of new
users (16% of SARs and 20% of seniors) persisted with treatment for a full
year. Median persistence survival with acarbose treatment was 79 days (95%
confidence interval [CI], 73-105 days) in SARs and 101 days (95% CI, 85-109
days) in seniors (P = .14 by log-rank test).
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Persistence with acarbose treatment.
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DETERMINANTS OF PERSISTENCE OF ACARBOSE TREATMENT
Table 2 provides crude and
adjusted rate ratios (RRs) and 95% CIs for determinants of persistence of
use of acarbose that were observed to be important in either of the 2 cohorts
based on Cox proportional hazards regression. In addition to the control variable
(duration of the index dispensation), the final Cox model included 5 variables
that were observed to be statistically significant and independent predictors
of acarbose persistence among seniors. In order of relative size (from largest
to smallest RR point estimate in a model predicting failure to persist), these
5 determinants included previous insulin use, initial daily acarbose dose,
consultation with a gastroenterologist after the index dispensation, CDS,
and prescribing physician (endocrinologist vs other). Only 1 of these (prescribing
physician) retained significance in the analysis in the SAR cohort, although
there was substantial overlap between cohorts in 95% CIs for the estimated
RRs associated with initial daily dose, gastroenterologist consultation after
the index dispensation, and CDS. Although only marginal differences were observed
between crude and adjusted RRs (Table 2), all RRs given below are adjusted (for the other predictors and
duration of the index dispensation) for between-cohort comparability.
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Table 2. Crude and Adjusted Rate Ratios From Cox Regression Analyses
Predicting Failure to Persist With Acarbose Treatment
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The strongest (highest RR) determinant among seniors, namely, previous
insulin use, was not an important predictor of persistence of use of acarbose
among SARs. Seniors who had received insulin in the year before their initial
acarbose dispensation were 1.59 times (95% CI, 1.24-2.04) less likely to persist
with treatment at any given time after the index dispensation (conditional
on survival until that time) than were seniors who had not received insulin
before acarbose. Analysis of the data from both cohorts combined suggested
that the difference between cohorts in the importance of the effect of previous
insulin use is a result of age rather than of any other (eg, socioeconomic)
difference between the cohorts. An interaction between the terms for previous
insulin use and age (as a dichotomous variable with a cutoff value of age
35 years) was statistically significant, and the overall model fit was identical
to a combined model in which age and its interaction with previous insulin
use were replaced by a variable for cohort. The effect of previous insulin
use on acarbose persistence is thus associated with (and limited to) advanced
age. Age was not an important explanatory variable in any of the within-cohort
analyses.
Seniors receiving their first prescription from an endocrinologist were
1.36 times (95% CI, 1.15-1.64) more likely to persist with treatment (ie,
the inverse of the RR predicting failure to persist) at any given time after
the index date than were those who received their first prescription from
an internist or other physician. Similarly, SARs receiving their first prescription
from an endocrinologist were 1.56 times (95% CI, 1.14-2.13) more likely to
persist with acarbose treatment than were those who received their first prescription
from another specialist.
Seniors who began taking acarbose at a higher daily dose (>100 mg) were
1.39 times (95% CI, 1.17-1.66) as likely to discontinue treatment at any given
time after the index dispensation (conditional on remaining on treatment to
that time) than were those who were started at a lower dose. In both cohorts,
only compliant renewers modified their initial daily dose. Among compliant
renewers, however, a similar majority of patients within each cohort maintained
their initial dose (59% of SARs and 60% of seniors). Of compliant-renewing
SARs, 2% reduced their acarbose dose and 39% increased their dose at some
point after the index date. Among compliant-renewing seniors, the respective
figures were 3% (reductions) and 37% (increases). These figures are consistent
with the fact that those who persisted tended to receive lower initial doses.
Seniors who consulted a gastroenterologist at some time within the observation
period after their initial acarbose dispensation were 1.31 times (95% CI,
1.03-1.67) more likely to discontinue treatment at any given time after the
index dispensation (conditional on having remained on treatment until that
time) than were those who did not consult a gastroenterologist during follow-up.
Each increment (on a 3-point scale) of chronic disease was associated
among seniors with a 1.16 times (95% CI, 1.01-1.32) higher probability of
persisting with acarbose treatment at any given time (ie, the inverse of the
RR for failing to persist).
Logistic regression analyses to predict renewal (by either definition:
ever or compliant renewal) of the first dispensation yielded the same set
of predictors as those discussed above based on the time-to-event analysis.
As expected, however, the dichotomous renewal outcomes resulted in less precise
RR (as odds ratio) estimates than did the modeling of the continuous outcome
of days of treatment (additionally adjusted for duration of index dispensation).
No substantive differences were observed between the results of the logistic
regression and time-to-event analyses.
COMMENT
Compliance can be broadly defined as "the extent to which the patient's
actual history of drug administration corresponds to the prescribed regimen."17 Persistence, as objectively defined herein, is the
duration of treatment during which minimal adherence (the proportion of pills
dispensed presumed to have been consumed) is 66%. The proportion of new acarbose
users who persisted for 1 year with what is intended to be lifelong treatment
was only 16% among SARs and 20% among seniors. Our definition of persistence
seemed to be robust, revealing similar (but more precise) predictors as those
observed in multivariate analyses of ever-renewal of the first dispensation
and what we termed "compliant renewal" of the first dispensation.
The population-based study of drug persistence using time-to-event methods
is a recent phenomenon; few peer-reviewed studies have been published and
none have addressed antidiabetic agents. Of drugs for which comparable data
exist, acarbose demonstrates among the lowest measured persistence. One-year
persistence was 35.6% in a cohort of Quebec seniors who began inhaled corticosteroid
treatment for chronic obstructive pulmonary disease in 199518
and 55% (amlodipine) and 63% (felodipine) in Quebec seniors started on 1 of
2 calcium channel blockers in 1990.19 Six-month
persistence was 80% to 89% for various antihypertensive agents in Saskatchewan
patients newly diagnosed as having hypertension between 1989 and 1994,20 compared with 32.8% for acarbose among Quebec seniors.
Only incontinence agents show lower persistence rates than does acarbose;
at 6 months persistence was 11.4% and 5.7% for oxybutynin chloride and flavoxate
hydrochloride,21 respectively, among Quebec
seniors started on 1 of 2 such agents between 1994 and 1997.
Among the 5 factors observed to be important bx;1predictors of acarbose
persistence in either cohort, only 1—prescribing specialist—was
predictive in seniors and SARs. The observation that patients who were prescribed
their initial dispensation by an endocrinologist were more persistent with
treatment might be indicative of greater persuasiveness of these specialists
or of inherent differences in compliance among patients referred to these
specialists.
Four factors (previous insulin use, initial daily acarbose dose, gastroenterologist
consultation after the index dispensation, and CDS) were predictive of acarbose
treatment persistence within the seniors cohort only. For 2 of these factors
(previous insulin use and initial daily acarbose dose), between-cohort differences
were statistically significant (P<.10 for interaction
terms between cohort and each of these factors in an analysis of the 2 cohorts
combined).
A relatively higher initial daily dose (>100 mg) was an independent
determinant of compliant acarbose treatment discontinuation among seniors
but not SARs, which is possibly suggestive of a greater susceptibility to
dose-dependent adverse effects among seniors. Such a suggestion is supported
by the additional importance (adjusted for initial daily dose and the 4 other
covariates) of the gastroenterologist consultation after the index dispensation
in this cohort. The finding of an important relative risk of consultation
with a gastroenterologist in the (minimum 4-month) period of observation after
the initial (index) acarbose dispensation in seniors (among whom none had
consulted a gastroenterologist in a minimum 1-year period antecedent to the
index dispensation) is surprising. This is perhaps because prescribing physicians
are inadequately informed of or are inadequately informing their patients
of the anticipated gastrointestinal tract adverse effects and the expected
diminution of these adverse effects over time.9
The importance of initial daily dose and a marker of gastrointestinal
tract adverse effects underscore the importance for clinicians to (1) start
patients on lower doses of acarbose, upwardly adjusting the dose gradually
as tolerance increases,22 and (2) discuss the
anticipated gastrointestinal tract adverse effects and their expected diminution
over time during acarbose treatment with prospective acarbose recipients to
improve persistence and prevent waste of health care resources on (a) prescriptions of acarbose to patients who are unlikely to persist
long enough to gain any benefit and (b) unnecessary
gastroenterologist consultations.2
This study of new acarbose users is subject to several limitations,
the most prominent of which are discussed in the following paragraphs. The
first limitation concerns the generalizability of the results of this study
to other periods and other regions. We cannot know whether the patients we
observed here, who were among the first diabetic patients in Quebec to be
started on treatment with the novel antidiabetic agent acarbose, are representative
of patients who might have been first given this agent in other places or
at other times (eg, at some later time with respect to the introduction of
the agent to the formulary).
The second limitation concerns the source of the data; we were limited
herein to information routinely collected in the provincial health plan's
administrative databases. The available data indicate only drugs dispensed
rather than drugs consumed. We could therefore infer persistence only from
the fact of continued (renewed) dispensations. We may thus have overestimated
persistence. Moreover, it is possible that some patients who received disbursements
of acarbose never actually took any of the medication.
Also unavailable to us was clinical information regarding the efficacy
of acarbose treatment in controlling blood glucose levels and qualitative
information such as one might ascertain from patient interview. Without the
former, it is not possible to verify whether patients stopped taking the medication
because of lack of efficacy. The latter would have provided insight into subjective
reasons for discontinuation of the drug use, such as a belief that the treatment
is ineffective or that the adverse effects were not balanced by enhanced feelings
of wellness.
In conclusion, the present analysis revealed low levels of persistence
of acarbose use, the first of the newest class of antidiabetic agents, among
SARs and seniors in the province of Quebec. In both populations, patients
who received their initial prescription from an endocrinologist as opposed
to an internist or other practitioner demonstrated better persistence with
acarbose treatment. Among seniors, patients with diabetes who demonstrated
better persistence with acarbose included those not dependent on insulin and
those who received a lower initial daily dose of the drug.
As emphasized by Urquhart,17 "substandard
compliance would be of only minor concern if it were not so prevalent or if
it were limited to medical conditions of a self-limiting or otherwise minor
nature." Studies such as the present one, which describe drug discontinuation
and its determinants, are an important first step to improving compliance
with an otherwise safe and effective drug.
AUTHOR INFORMATION
Accepted for publication October 25, 2000.
This study was supported by a grant from Bayer Inc, Etobicoke, Ontario.
We gratefully acknowledge the helpful comments of J. L. Chiasson, MD,
and E. Rahme, PhD, and the administrative support of Anita Massicotte. We
also thank C. Kapetanakis, MSc, of the Régie Régionale de la
Santé et des Services Sociaux de Montréal-Centre for his assistance
with the identification and interpretation of Quebec survey data regarding
the prevalence of diabetes.
Corresponding author: Jacques LeLorier, MD, PhD, Pharmaco-Epidemiology
and Pharmaco-Economics Research Unit, Research Centre, Hôtel-Dieu de
Centre Hospitalier de l'Université de Montréal, 3850 St Urbain
St, Montreal, Quebec, Canada H2W 1T8 (e-mail:
jacques.le.lorier{at}umontreal.ca).
From the Pharmaco-Epidemiology and Pharmaco-Economics Research Unit,
Hôtel-Dieu de Centre Hospitalier de l'Université de Montréal,
Montreal (Drs Catalan and LeLorier), and Hôtel-Dieu de Lévis,
Centre Hospitalier affilié a l'Université Laval, Quebec (Dr
Couture), Quebec.
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