In this study of older old patients admitted to a geriatric ward, GLT at home was appropriately prescribed in only 1 in 4 patients. GLT appropriateness was not associated with any patient’s characteristic but with GLT prescribing, i.e. lower use of hypoglycaemic agents (i.e. insulins, sulfonylureas or glinides) and of intense dose. GLT undertreatment concerned 1 in 6 geriatric patients, in whom HbA1c was too high despite high dose of GLT. GLT overtreatment, i.e. patients prescribed with hypoglycaemic agents with a HbA1c value below the target range, was detected in 1 in 2 patients. GLT overtreatment was associated with poor health status, severe renal failure and use of bi-or tri-therapy of GLT. Importantly, one-year mortality was higher in patients with GLT overtreatment (44%) than those with appropriate GLT, independently of the patient’s health status and of the age of the patient.
GLT overtreatment, which potentially leads to hypoglycaemia [14, 15] and thus to associated comorbidities and mortality [2], was surprisingly not less frequent in patients with geriatric syndromes or poor health status than others. This finding highlights in this population a clear lack of individualisation of GLT according to these characteristics. This is even more surprising since older patients with geriatric features or/and in poor health status are at higher risk of more frequent and severe hypoglycaemic events, due to frequent misdiagnoses, unawareness and atypical presentations [2]. In our study, GLT overtreatment was more frequent in patients with severe renal failure (eGFR< 30 ml/min), most of whom (n = 47/51; 92.2%) received at least one hypoglycaemic agent (i.e. insulins, sulfonylureas or glinides). One potential explanation is the contra-indication of metformin in patients with severe renal failure. In addition to the fact that some hypoglycaemic agents can accumulate in case of severe renal failure (e.g. sulfonylureas [16]), other non-hypoglycaemic GLT agents are preferable, such as DPP4-inhibitors, the safety of which (with adjusted doses for some) has been studied in case of severe renal impairment even in older patients [10, 17].
Patients with GLT undertreatment might benefit from GLT intensification in order to avoid discomfort of hyperglycaemia-related symptoms. Beyond the value of HbA1c, the decision to intensify the treatment should be taken with caution. Indeed, hypoglycaemic events can also occur despite high HbA1c values in patients receiving intensive hypoglycaemic therapy [18]. Therefore, in the geriatric patients with a HbA1c over the target level, GLT intensification should be achieved on a case-by-case basis, considering a risk-benefit balance between the discomfort of hyperglycaemia and the risk of hypoglycaemic events. Furthermore, considering that the very old and frail population of this study received highly conservative GLT agents (largely composed by metformin and hypoglycaemic agents), non-hypoglycaemic agents other than metformin could be an interesting option, if further intensification of the treatment is deemed necessary.
The one-year mortality rate was high in these patients (38.5%). In the multivariate model, one-year mortality was higher in the presence of poor health status, low weight and GLT overtreatment, but lower in the presence of multiple falls. The latter association might be explained by the fact that the very dependent geriatric patients do not walk anymore. Falls might indicate a somewhat preserved functional status. The association between one-year mortality and GLT overtreatment is important to discuss. This observation does not mean that GLT overtreatment increases mortality in geriatric patients, as it has been demonstrated in other studies involving younger old and healthier patients [19,20,21]. Indeed, the observational design of our study does not allow any causal conclusion. Frailty and severe renal failure might be confounding factors, as they are associated to both GLT overtreatment and mortality. However, the observed association between one-year mortality and GLT overtreatment highlights the pointlessness and the risk of intense GLT in geriatric patients with poor health status with a poor one-year life expectancy. It is indeed useless to prescribe an intense GLT therapy with the aim to avoid long-term T2D complications in patients with a short life expectancy, especially since such a therapy induces hypoglycaemic events.
This study was limited by its retrospective design. The duration of diabetes is not known. Data related to the GLT prescribers (e.g. motivations for initiating/continuing this treatment, knowledge about the guidelines on diabetes in older adults) could not be collected. The association of GLT appropriateness with other outcomes that matter to the geriatric patients, i.e. impaired quality of life, hypoglycaemic episodes, functional decline, should be studied in the future. This study was finally limited by its single-centre inclusion, which, despite the risk of selection bias, is to be put into perspective given the continuous inclusion of patients over a long period of time during which several different medical teams succeeded one another.
A strengths of this study is the focus on geriatric patients with type 2 diabetes ≥75 years in the setting of a geriatric ward of a university hospital. Geriatric patients are the most dependent with the most unfavourable health status among older patients (e.g. no patients in this study was in good health status). Therefore, these data cannot be generalised to the general older population ≥ 75 years. However, these data are important for patients from this particular setting, especially as these patients are not commonly represented in the scientific literature on the treatment of type 2 diabetes. Other strengths were the collection of data on the main geriatric syndromes, the tailoring of HbA1c targets according to the 2019 Endocrine Society guideline, and the analysis of the residual life expectancy (vital status at 1 year).
This study confirms the need for an improvement in GLT prescribing in the geriatric patients with T2D. Several actions should be considered. Firstly, the prescribing physician should individualise the HbA1c targets in each older patient based on the health status and the use of hypoglycaemic therapy (i.e. insulins, sulfonylureas or glinides), as suggested by the Endocrine Society. As pointed by most of the recent clinical guidelines on older adults with diabetes, the tailoring of HbA1c is the most effective way to reduce inappropriate therapy and the ensuing risk of hypoglycaemia [10, 22,23,24]. It is acknowledged that the implementation of guidelines takes time. However, the results of this study highlight the existence and relevance of guidelines related to the individualised management of glucose-lowering therapy, in particular the 2019 Endocrine Society guideline, and to use patients’ health status and the use of hypoglycaemic agents to individualise GLT according the patient’s target HbA1c level. Secondly, the patients should be involved in the decision making process as much as possible [10]. Finally, in the numerous geriatric patients with GLT overtreatment, de-intensification of hypoglycaemic agents (i.e. stopping the medication, reducing the dose or switching to another and safer drug) should be performed especially in patients with a poor overall health status (with frail profile, dementia, cognitive impairment) [25]. Actually, life expectancy of these patients is reduced and the benefit of intensive glucose lowering therapy is therefore absent. Interventional studies are deeply needed to clarify the modalities of GLT de-intensification in older people with type 2 diabetes.