Frailty is described as a metabolically heterogeneous condition with at least two different phenotypes. Physicians should tailor the choice of hypoglycemic agents in frail older people with type 2 diabetes mellitus to suit each type. They must consider new therapies of GLP-1RAs and SGLT-2 inhibitors early in the sarcopenic obese (SO) but avoid it in the anorexic malnourished (AM) phenotypes. However, they must consider insulin early in the AM but see it as a last resort in the SO phenotypes. 

Glycemic control remains based on function, with tighter targets in less frail and relaxed goals in severely frail individuals. However, physicians must consider GLP-1RAs and SGLT-2 inhibitors in the SO phenotype, irrespective of function, due to their prognostic benefit independent of glycemic control. 

Future research must characterize the metabolic properties of frail older people with diabetes to help precisely tailor hypoglycemic treatment. A recent study has illustrated five subtypes of patients with type 2 diabetes with different characteristics, insulin resistance, disease progression, and risk of diabetes-related complications, which is a step toward practicing precision medicine. Additionally, novel glucose-lowering agents with a positive effect on frailty are still needed.

Ahmed H. Abdelhafiz, Daniel Pennells & Alan J. Sinclair (2022) A modern approach to glucose-lowering therapy in frail older people with type 2 diabetes mellitus, Expert Review of Endocrinology & Metabolism, 17:2, 95-98, DOI: 10.1080/17446651.2022.2044304