Adherence to antihyperglycemic treatment: a work in progress

KEYWORDS:

• Type 2 diabetes mellitus
• adherence
• compliance
• antihyperglycemic treatment
• insulin analogs
• human insulins

Type 2 diabetes mellitus (T2DM) is a major public health problem. The prevalence of T2DM is increasing worldwide, driven by the aging of the population and the pandemic of obesity [1]. The microvascular complications of T2DM represent the leading cause of end-stage renal disease, blindness, and nontraumatic amputation in high-income countries [1]. In addition, T2DM is also a major risk factor for cardiovascular disease (CVD) and patients with T2DM appear to have comparable all-cause mortality with patients with established CVD [1]. On the other hand, tight glycemic control reduces the risk of development and progression of diabetic nephropathy, retinopathy and neuropathy [2]. Accumulating data also suggest that antihyperglycemic treatment might also reduce cardiovascular morbidity and mortality in patients with T2DM [3].

Despite these beneficial effects of glycemic control, several studies showed that adherence to antihyperglycemic treatment is suboptimal in patients with T2DM. Nonadherence to oral antidiabetic agents, defined as a medication possession ratio <0.8, ranges between 13% and 31% [4,5]. Interestingly, adherence rates to oral agents appear to be lowest with metformin, the first-line agent for management of T2DM [4]. However, other studies did not identify differences in adherence to metformin, sulfonylureas, and pioglitazone [6]. Importantly, adherence to fixed-dose combinations of oral antidiabetic treatments is better than adherence to free drug combinations [7]. Not surprisingly, nonadherence to treatment is consistently associated with poorer glycemic control; HbA_1c levels are higher by 0.4–0.7% in nonadherent compared with adherent patients [4]. Younger age, female sex, lower education, lower income, and higher out-of-pocket costs are independently associated with lower adherence to antihyperglycemic treatment [5]. Lower daily total pill burden and nonendocrinology specialist prescribers versus primary care also predict suboptimal adherence [5]. Patients with a recent diagnosis of T2DM and those who belong to ethnic minorities are also less adherent to treatment [5,8].

Regarding adherence to insulin treatment, more than one third of patients report omission of insulin on a mean of 3 days per month [9]. Male gender, younger age, increased cost, and more frequent hypoglycemic episodes are associated with suboptimal adherence to insulin treatment [9]. Previous studies reported that adherence is better in patients using premixed insulin and basal insulin compared with those using a basal bolus regimen [10]. In the present issue of Expert Opinion on Pharmacotherapy, the results of the first study that compared adherence to human insulin with analogue insulin are reported [11]. It is well established that analogue insulins are similarly effective in glucose-lowering compared with human insulins and are also associated with lower risks of hypoglycemia [12]. However, adherence was similarly low in human and analogue insulin in the present study (70.5 and 68.1%, respectively) [11]. In agreement with previous reports, lower levels of education and younger age predicted suboptimal adherence to insulin treatment [11]. Given that analogue insulins are more expensive than human insulins, it is possible that this reduced risk of hypoglycemia counteracts the negative effects of the increased cost on adherence [11]. However, neither cost nor frequency of hyperglycemia was evaluated in the present study [11].

Overall, the present and previous studies highlight a pressing need to improve adherence to antihyperglycemic treatment. Several interventions appear to be useful tools for achieving this target, including education, monitoring, participatory decision-making, and sending reminders [13,14]. However, no single intervention has been consistently shown to improve adherence and to improve glycemic control, suggesting that multiple interventions and individualized approaches might be needed [13]. It is important to bear in mind that even though nonadherence to medication is associated with lower pharmacy and outpatient costs in patients with T2DM, it considerably increases in-hospital costs resulting in a significant net increase in total health-care costs [15]. Therefore, concerted efforts from health-care professionals are needed to improve adherence to antihyperglycemic agents, which will translate into reduced rates of both microvascular and macrovascular complications in patients with T2DM.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.