4. Discussion
4. 1 Principal findings and their
relationship with the
literature
The prevalence of polypharmacy in people treated for diabetes increased
from 56.5% in 2012 to 58.2% in 2016. Significant increases were seen
in all age groups with the highest absolute increase in the group of
55-64 years old. The prevalence of older people with at least one PIM
decreased around 3% in the study period. In the middle-aged group, the
prevalence increased around 2% from 2012 to 2015, then it decreased 1%
afterwards. The use of long-term high-dose PPI, benzodiazepines, and
strong opioids without laxatives were the most common PIMs in people
with diabetes in both age groups, with gradual increases over time for
PPIs and opioids without laxatives, and decreases for benzodiazepines.
Furthermore, the use of TCAs was common in the older age group, with an
increase over time.
The findings of this study confirm that polypharmacy is a concern in
people with diabetes, with the highest rate in older-age patients
[8,18,19]. The increasing trend of polypharmacy in the diabetes
population was similar to the trend in the general population [2,3].
The polypharmacy prevalences in people with diabetes, ranging from 36%
in the 45-54 years old to 65% in those aged ≥65 years in 2012, were
substantially higher than the prevalence seen in the general population
at that time [2]. Previously, an increase of polypharmacy was seen
in the middle-aged people [2,3], and likewise we observed this in
people with diabetes. A noteworthy finding was that the absolute
increase in the 55-64 years old was larger than in the group of 65 years
and older. This may indicate an increase in the number of co-morbidities
in this age group, which is followed by an increase in prescribing of
medication. Whether less increase in the older age group means less
increase in co-morbidities or more restrictive prescribing remains
unknown. For middle-aged patients, prescribers may not yet see
polypharmacy as a large burden or problem. So far, attention for
polypharmacy management is more focused on older than middle-aged people
[20].
Our study showed that while polypharmacy increased for people with
diabetes between 2012 and 2016, the prevalence of PIM in older patients
with polypharmacy decreased in this period. This suggests that the
continuing attention and many initiatives to decrease inappropriate
polypharmacy in older patients have had an effect in this population
[21]. Studies in the general population using Beers criteria also
showed decreasing trends in the annual PIM prevalence between 1995 and
2004 in France [22], and between 2007 and 2014 in US [23].
Interestingly, a slight increase in PIM was observed in the beginning of
our study period in the middle-aged people with polypharmacy, with the
highest PIM prevalence of 39% in 2014. In 2015, there was a slight
decrease and the significant quadratic trend may indicate the beginning
of a decline in PIM in this middle-aged group. Further data from recent
years are needed to support this finding. The PIM prevalences of 37-39%
we observed in middle-aged diabetes patients with polypharmacy are of
concern. Other studies which used PROMPT criteria in middle-aged people
showed PIM prevalences ranging from 21% to 43% in community-dwelling
people [24,25]. Although these numbers are difficult to compare due
to differences in setting and assessment of the PROMPT criteria, they
underline the importance of focussing on inappropriate polypharmacy in
the middle-aged group.
The use of long-term high-dose PPIs, benzodiazepines, and strong opioids
without laxatives was common in both age groups. The prevalence rates
when applying the same PROMPT criteria were around 1-2% higher in the
younger as compared to the older patients. Similar common PIMs have been
found in a general middle-aged population using PROMPT criteria
[25]. In the general older-age population, benzodiazepines were also
among the most prevalent PIMs, with the prevalence rates ranging from
0.74% to 3.9% [22,26]. The other most common PIMs when assessed
using Beers criteria were from opioid group, antidepressant group, and
digoxin [22,23,26]. Our findings indicate that prescribers appear
not to be more cautious with prescribing these PIMs in older people with
or without having diabetes. Apparently, substantial numbers of people
with diabetes require these drugs according to their physicians. Chronic
insomnia and anxiety are highly prevalent in people with diabetes
[27,28], and benzodiazepines can be prescribed to treat those
problems. Proton-pump inhibitors are considered as well-tolerated drug
classes for treating and preventing acid-related disorders. However, the
use of PPIs above maintenance dosage was identified to increase the risk
of chronic kidney disease in diabetic population [29]. The reason
for not adding a laxative in diabetes patients using opioids is also of
concern, since they may already have a higher risk for constipation
[30]. A possible reason for not prescribing laxatives could be that
patients are sufficiently managed with dietary measures or
over-the-counter (OTC) drugs, or that patients experience insufficient
benefits from laxatives [31]. Benzodiazepines were frequently
prescribed but the prevalence decreased in the study period. This may be
part of a downward trend seen in the use of these drugs in the general
population in the Netherlands [2]. Since 2009, reimbursement for
benzodiazepines has been restricted in the Netherlands to discourage
overuse of these drugs. On the other hand, for the other common PIMs
-i.e., long-term high-dose PPIs, strong opioids without laxatives, and
TCAs in older patients- some increases were seen, despite
recommendations in the Dutch national guidelines against such use
[32]. It is disappointing that in people with diabetes, who already
have a high medication burden, we do not see a more restricted use in
the study period.
Strength and limitation
This study is unique in providing detailed insights into the prevalence
of polypharmacy and PIM in older and middle-aged people with diabetes. A
large pharmacy database was used which includes all outpatient
prescriptions for people registered with the participating pharmacies.
In the Netherlands, most people collect their medication from one
pharmacy, where they are registered. There are some limitations. First
of all, some PIM criteria, particularly from the Beers list, require
clinical information which is not available in a pharmacy database. This
is likely to lead to lower estimates of the overall PIM prevalence
compared to other studies. On the other hand, many different PIM lists
have been developed, and usually adaptations and selections have to be
made depending on the setting and the medication available in a country
[33]. Second, the pharmacy database provides information about
dispensed drugs, which may not reflect actual use and thus exposure to
the PIM, and does not provide data on drugs used during hospitalisation.
Finally, we do not know whether patients used OTC drugs, which might
include laxatives. We expect, however, that for chronic use such
laxatives would be dispensed on prescription, allowing for
reimbursement.