Newer anti-diabetic therapies with low hypoglycemic risk-potential advantages for frail older people

Abstract

ABSTRACT The prevalence of diabetes is increasing due to increasing aging of the population. Hypoglycemia is a common diabetes-related complication in old age especially in patients with multiple comorbidities and frailty. Hypoglycemia and frailty appear to have a bidirectional relationship reenforcing each other in a negative downhill spiral that leads to an increased risk of adverse events including disability and mortality. The incidence of hypoglycemia in this age group is usually underestimated due to its atypical clinical presentation and difficult recognition by health care professionals. Guidelines generally recommend a relaxed glycemic control in frail older people with diabetes mainly due to the fear of anti-diabetic medications-induced hypoglycemia. The new anti-diabetic therapies of sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon like peptide-1 receptor agonists (GLP-1RA) have consistently shown a cardio-renal protective effect independent of their glycemic control. Contrary to the traditional hypoglycemic agents that either increase insulin stimulation or insulin sensitization with a potential hypoglycemic risk especially sulfonylureas, the new therapies have a novel anti-diabetic mechanisms of action that have a negligible risk of hypoglycemia. The new therapies appear to be both effective and well tolerated in old age. With appropriate patients’ selection, most older people will be eligible for the new therapies if well tolerated and no contraindications. In frail older people, we suggest a pragmatic approach of the use of the new therapies based on the concept of the weight status rather than the frailty status. Frail patients with normal or excess weight are likely to gain most from the new therapies due to its favorable metabolic properties in this group, while the use in the underweight frail patients should be largely avoided especially in those with persistent anorexia and weight loss.