Inhibition of the sodium-glucose co-transporter 2 in the elderly: clinical and mechanistic insights into safety and efficacy

Abstract

SUMMARY The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of antidiabetic therapy that inhibits glucose and sodium reabsorption on renal proximal convoluted tubule. Its effect is well demonstrated in various clinical scenarios in the younger population. This review and metanalysis describe particularities of the SGLT2i on the elderly, with mechanistic insights of the potential benefit and remaining challenges about the use of these drugs in this important age group. Further, we will present a meta-analysis of the main effects of SGLT2i reported in post-hoc studies in which the median age of the subgroups analyzed was over 60 years. Despite the absence of specific clinical trials for this population, our findings suggest that SGLT2i therapy on older individuals is effective to lower glucose and maintain its effect on systolic blood pressure and body weight.

Ageing‐associated increase in SGLT2 disrupts mitochondrial/sarcoplasmic reticulum Ca2+ homeostasis and promotes cardiac dysfunction

“…This view is supported by recent clinical studies, demonstrating the use of metformin along with SGLT2 inhibition, in elderly patients 41,42 . Further, several clinical trials have demonstrated the beneficial effects of SGLT2 inhibitors on reducing cardiac morbidity risk of heart failure in the aged population 10‐12,43 …”

Sodium–glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus

“…SGLT2i therapy in older individuals was effective at lowering glucose and maintained its positive effect on body weight and systolic blood pressure, as shown in a meta-analysis of post hoc studies in which the median age of the subgroups analysed was >60 years 102 . However, specific RCTs that evaluated both the efficacy and safety of SGLT2is in the elderly population, especially in patients >75 years, are still lacking and only very limited data have been published in observational studies 103 .…”

Sodium–glucose transporter-2 inhibitors for prevention and treatment of cardiorenal complications of type 2 diabetes

“…Nearly 50% of patients with T2D are 65 years old or older [8]. In older patients, treatment with SGLT-2i is effective at lowering glucose, body weight and systolic blood pressure, as shown in a meta-analysis of post-hoc studies in which the median age of patients was > 60 years [56]. On the other hand, specific trials that evaluated both the efficacy and safety of SGLT-2i in older patients with T2D, especially in those > 75 years, are still lacking and only very limited data are available from observational studies [57].…”