‘One-size-fits-all’ treatment targets harm frail older patients with diabetes

Around 425 million people around the world are thought to have type 2 diabetes mellitus^[1]
, and older people aged 80 years and over account for a growing proportion. In the UK, an estimated 13% of the population living with diabetes is aged over 80 years — equivalent to a fifth of people in this age group^[2]
.

There are substantial physiological differences between frail older patients and the typically studied ‘young elderly’. Frailty is associated with failing kidney and liver function and reduced incretin effect. Autonomic nervous regulation deteriorates, cognition declines and pulmonary gas exchange is attenuated. Traditional complications of diabetes (such as retinopathy, nephropathy, ischaemic heart disease and stroke) can still occur in older people, but these conditions account for fewer than half of diabetes-related disabilities observed in this group^[3]
. Premature cognitive decline, increased frailty and sarcopenia (muscle loss) are recognised as the important new complications of diabetes for these people.

Despite these differences, older patients are systematically excluded from clinical trials, either based on an arbitrary age cut-off, multiple comorbidities, polypharmacy, cognitive impairment or reduced life expectancy; only 1.4% of diabetes clinical trials specifically include older adults^[4]
.

So, until recently, the majority of older adults were treated to the same targets — with the same agents — as their younger counterparts. To date, only one study has assessed the feasibility of individualising targets for older adults^[5]
. In this trial, investigators were provided with extensive training in assessing frailty, and a mandate to provide a holistic assessment (including measures of frailty, comorbidities, polypharmacy, age and baseline HbA_1c) in adults aged 70–97 years. But investigators established an average target HbA_1c of 53mmol/mol (7.0%) — a target aligned with guidelines aimed at younger people^[5]
. To achieve this target, a multitude of drugs are often prescribed, with little evidence of benefit within the individual’s lifetime.

Hypoglycaemia and older adults

Managing hyperglycaemia is complicated by the risk of hypoglycaemia, which is, in turn, associated with an increased risk of vascular events, hospitalisation and premature vascular mortality in the general population with diabetes. Guidelines recommend that, where possible, attempts should be made to mitigate this risk by choosing agents with the lowest risk of hypoglycaemia, such as DPP-4 inhibitors, GLP-1 analogues, SGLT-2 inhibitors and analogue insulins.

In older adults, however, as kidney function declines (and causes accumulation of some drugs and sarcopenia), insulin resistance declines, as well as the amount of tissue requiring insulin. Therefore, patients who have previously been stable and well-controlled have falling mean glycaemia and elevated risk of hypoglycaemia. Evidence suggests that the relationship between these risks and the overall outcomes is stronger in older people than younger people. For example, in a large observational cohort study of 16,667 older adults with diabetes, a single hypoglycaemic episode (hypo) was associated with a 26% increased risk of cognitive impairment even after adjustment for various factors^[6]
. An individual experiencing three or more hypos had almost twice the risk of future dementia. Those with pre-existing cognitive impairment had a four-fold increased risk of a severe hypo. Hypos are also associated with a 45–70% increased risk of fall-related fracture in people aged over 65 years^[7]
, and with increased risks of cardiovascular events and cardiovascular mortality^[8]
.

Systematic issues related to drug understanding and administration in rigid protocols also increase the risk of hypoglycaemia and its consequences in frail patients, particularly when administration is dependent on support from other healthcare professionals, such as health visitors, district nurses or community matrons^[9]
. There is evidence that HbA_1c may be artificially higher in older adults owing to red-cell fragility^[10]
. As a result, patients who are treated to the same target will require a lower average and fasting blood glucose, which further increases the risk of intermittent hypoglycaemia. Furthermore, frail older adults are not as sensitive to the effects of adrenaline and glucagon as their younger counterparts. As a result, hypoglycaemia often goes unrecognised. Older people may present with symptoms of neuroglycopenia rather than with the classic coldness, sweatiness and palpitations that usually triggers suspicion. The non-specific symptoms, such as vague light-headedness, impaired balance and acute confusional states, can often be misinterpreted as progression of frailty or related conditions, such as transient ischaemic attacks or urinary tract infections^[11]
.

Drivers of over-treatment of older patients

The introduction of the general medical services (GMS) contract in 2004 for GPs in the UK incentivised glycaemic control as part of the quality outcome framework. This ‘payment by results’ approach led to an overall improvement in the blood pressure and glycaemic and lipid control in people with diabetes across the UK. But the contract did not differentiate based on age, limited life expectancy or frailty. Until recently, there were no rules for stopping long-term therapy. As a result, a significant proportion of older adults were commenced on agents more than ten years ago to improve glycaemic control and, despite significant changes in patients’ overall wellbeing and physical status, these medicines have not been reviewed.

More than a decade of ‘treat to target’ and ‘outcome-based funding’ has resulted in many algorithms that do not fully consider the individual requirements of older adults. A focus on traditional targets detracts from the importance of optimising quality of life or preparing for end-of-life scenarios^[12]
,[13]
.

Several international guidelines provide useful frameworks for enhancing diabetes care for this population, but they are based predominantly on consensus and opinion. Many of these contain an indication of workable metabolic targets for older adults^{[12]
,[14]
,[15]}
; however, these have failed to have a widespread impact on glycaemic control in older people in the UK.

Deprescribing towards appropriate targets

The launch of national guidance on the assessment and management of frailty in older people with diabetes is timely, and highlights the measures now needed within the NHS to create a frailty–diabetes care pathway^[16]
. The guidance has been endorsed by the National Institute for Health and Care Excellence and was incorporated into the 2019 GMS contract; all people aged over 70 years require assessment for frailty and subsequent de-escalation of interventions if necessary.

Frailty can be assessed with minimal additional training. The timed ‘up and go’ test uses the time a person takes to rise from a chair, walk three metres, turn around, walk back to the chair and sit down to estimate their frailty^[17]
. The test can be conducted in the patient’s home, a GP surgery or the community pharmacy without sophisticated equipment and provides valuable prognostic information. If a person with diabetes cannot perform the test within an age-appropriate time, there are significant implications for life expectancy and therefore treatment targets. If a person is deemed as frail, more appropriate targets should be set and current treatments should be reviewed.

Pharmacists reducing diabetes overtreatment

Community pharmacists are a respected source of information on medicines and their knowledge can be utilised in chronic disease management. With the advent of electronic health records, there is a growing interest from NHS England in assessing the pharmacist’s role in improving outcomes for older adults with diabetes^[16]
.

Using the electronic health record, pharmacists may be in a position to withdraw therapy that is known to be associated with a high risk of hypoglycaemia. Medicines should be stopped in partnership with the appropriate primary care professional; however, GPs often welcome support with deprescribing potentially harmful drugs.

In early 2020, several projects are due to report explorations of the community pharmacist’s potentially significant role in facilitating the deprescription of unnecessary medicines and the impact of these partnerships on frail older patients with diabetes.