The outcome of frailty in older people with diabetes as a function of glycaemic control and hypoglycaemic therapy: a review.

Introduction: Frailty is an emerging and newly recognized complication of diabetes in older people. However, frailty is not thoroughly investigated in diabetes outcome studies.

Areas covered: This manuscript reviews the effect of glycemic control and hypoglycemic therapy on the incidence of frailty in older people with diabetes.

Expert opinion: Current studies show that both low glycemia and high glycemia are associated with frailty. However, most of the studies, especially low glycemia studies, are cross-sectional or retrospective, suggesting association, rather than causation, of frailty. In addition, frail patients in the low glycemia studies are characterized by lower body weight or lower body mass index (BMI), contrary to those in the high glycemia studies, who are either overweight or obese. This may suggest that frailty has a heterogeneous metabolic spectrum, starting with an anorexic malnourished (AM) phenotype at one end, which is associated with low glycemia and a sarcopenic obese (SO) phenotype on the other end, which is associated with high glycemia. The current little evidence suggests that poor glycemic control increases the risk of frailty, but there is a paucity of evidence to suggest that tight glycemic control would reduce the risk of incident frailty. Metformin is the only well-studied hypoglycemic agent, so far, to have a protective effect against frailty independent of glycemic control in the non-frail older people with diabetes. However, once frailty is developed, the choice of the best hypoglycemic agent for these patients will be affected by the metabolic phenotype of frailty. For example, sodium glucose transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are appropriate in the SO phenotype due to their weight losing properties, while insulin therapy may be considered early in the AM phenotype due to its anabolic and weight gaining benefits. Future studies are still required to further investigate the metabolic effects of frailty on older people with diabetes, determine the most appropriate HbA1c target, and explore the most suitable hypoglycemic agent in each metabolic phenotype of frailty.