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.