The focus and mainstay of managing patients with diabetes will (and should) be reducing hyperglycemia. There is clear evidence from the UK Prospective Diabetes Study of the benefits of this in patients with type 2 diabetes. However, the incessant drive to lower glycated hemoglobin (HbA1c; eg, driven by the Quality and Outcomes Framework in UK Primary Care) is not without concern and risks. Whilst the lowering of HbA1c to a target of 6.5% (48 mmol/mol) may be optimal for those with recent onset of diabetes and a low burden of comorbidity, for those treated with insulin and/or sulfonylureas this target may result in increase in the frequency of hypoglycemic episodes. This is especially of concern in vulnerable groups such as the elderly, and those with impaired cognition and frailty.
Concerns from clinical trials
Trials such as ACCORD, ADVANCE, and VADT were key in highlighting concerns with intensive management of patients. In the ACCORD trial, patients were randomized to receive intensive treatment aiming for HbA1c of below 6% (43 mmol/mol). The study was stopped prematurely due to findings of increased mortality in the intensive group. The mean (± standard deviation) age was 62.2±6.8 years; the intensive group had a higher incidence of hypoglycemia (annualized rates of 3% vs 1% in the less intensive group) [1]. However, while two other trials of intensive control in older patients with type 2 diabetes, the ADVANCE and VADT trials, did observe an increase in hypoglycemic and severe hypoglycemic episodes, no increase in mortality was observed [2, 3].
Adverse effects of hypoglycemia
Severe hypoglycemia is a significant contributor to mortality and morbidity, and the consequences can be short or long term. Acute episodes can result in falls and injury, the effects of which can be mild, such as loss of confidence and bruising, to life-threatening head injuries, seizures, and fractures, often leading to prolonged hospital admission. Other potential risks include the so-called "dead in bed" syndrome of hypoglycemia resulting in arrhythmia and cardiovascular death [4, 5].
Though often associated with elderly patients, many complications of hypoglycemia are of equal concern in younger people with diabetes, in whom long-term frequent hypoglycemia may increase the risk of cardiovascular mortality [6]. An analysis of hypoglycemia and cardiovascular mortality looking at prospective data for 195 patients with confirmed severe hypoglycemia over a median 15.3 years found that those with at least one severe hypoglycemic episode had a higher risk of coronary heart disease, and cardiovascular and cancer mortality [7].
Risks of overtreatment
Overtreatment in diabetes is an under-recognized concern. A retrospective cohort study looking at adults with type 2 diabetes found that over three-quarters of patients with HbA1c less than 6% (43 mmol/mol) had frailty or multiple comorbidities [8]. A more recent analysis of overtreatment in an elderly Dutch cohort found that just over 20% of patients who were overtreated had hypoglycemia and 30% had falls [9].
Not only does overtreatment increase the risk of hypoglycemia and the associated effects, it also adds to pill burden, with polypharmacy a known poor prognostic indicator; the unnecessary medication also has economic implications [10].
Do the guidelines help?
Guidelines, specifically those from the International Diabetes Federation [11] and the American Diabetes Association (ADA) Standards of Care [12], address the issues of treatment targets in older adults and acknowledge the risks associated with intensive management. The ADA guidance is clearer than most other guidance on targets, suggesting an HbA1c target of <7.5% (58 mmol/mol) in generally well older adults, with laxer targets of <8% (64 mmol/mol) and 8.5% (69 mmol/mol) with increasing comorbidities and reducing life expectancy [12].
Guidance from the UK's National Institute for Health and Care Excellence, though not giving specific values, suggests relaxation of targets in the frail adult with multi-morbidity or reduced life expectancy on a case by case basis. They mention a target of 7% (53 mmol/mol) for patients on medication known to increase risk of hypoglycemia; however, this can be further relaxed based on the previously mentioned considerations [13]. Currently, there are no specific sections or directions for management of the older adult.
More recently, guidance has been published on managing the frail elderly person with diabetes [14]. The guidance specifically targets the older adult with diabetes and frailty and addresses HbA1c and random glucose targets in individuals. Similar to the ADA guidance, an HbA1c target of 7–8% (53–63 mmol/mol) is suggested in the moderately frail and 7.5–8.5% (58–68 mmol/mol) in the more severely frail. They also suggest a random glucose target of between 6.7–11.1 mmol/L in those where HbA1c is not appropriate. Though practical and certainly useful, it is important to note that there is still limited evidence for these targets, with most recommendations being consensus decisions with a need for more research in this area.
When is deintensification appropriate?
The term deintensification is often used to highlight the need to review medications and consider less aggressive medication regimes in individuals. Though there are sensible guidelines, the real-life implementation and robust evidence behind this is limited. A pragmatic approach to the older adult with diabetes is necessary and perhaps targeting of higher risk, frailer groups with a focus on deintensification (particularly in patients taking sulfonylureas or insulin) in the primary care setting, either in care homes or in targeting specific populations, is an ideal first step towards addressing this issue.
Thus, despite HbA1c reduction being a cornerstone of diabetes management, care and attention should be given to avoidance of overtreatment and use of inappropriate treatments in certain vulnerable groups by deintensification. Careful medicines management and holistic care should supersede target-driven care for these vulnerable groups.