Management of Type 2 Diabetes in Frail Older Adults.

Aging is one of the most important factors associated with the dramatic increase in the prevalence of type 2 diabetes mellitus (T2DM) globally. In addition to traditional micro- and macrovascular complications, diabetes mellitus (DM) in older adults is of great importance due to its independent relationship with frailty, which is defined as a decline in functional reserves and vulnerability to stressors. Frailty assessment enables the determination of biological age, thus predicting potential complications in older adults and identifying tailored treatment strategies. Although the latest guidelines have acknowledged the frailty concept and provided recommendations specific to this subgroup of older adults, frail older adults are particularly considered only as anorexic, malnourished people for whom relaxed treatment targets should be set. However, this approach bypasses other metabolic phenotypes in the context of diabetes and frailty. Recently, a spectrum of metabolic phenotypes in the context of frailty in DM was suggested, and the two edges of this spectrum were defined as "anorexic malnourished (AM)" and "sarcopenic obese (SO)." These two edges were suggested to require different strategies: Opposite to the AM phenotype requiring less stringent targets and de-intensification of treatments, tight blood glucose control with agents promoting weight loss was recommended in the SO group. Our suggestion is that, regardless of their phenotype, weight loss should not be the primary goal in DM management in older adults who are overweight or obese, because of the increased malnutrition prevalence in older adults suffering from DM compared with standard older adults. Furthermore, overweight older adults have been reported to have the lowest risk of mortality compared with other groups. On the other hand, obese older individuals may benefit from intensive lifestyle interventions including caloric restriction and regular exercise with the assurance of at least 1 g/kg/day high-quality protein intake. Besides metformin (MF), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) or glucagon-like peptide-1 receptor agonists (GLP-1RA) should be considered in appropriate SO cases, due to high evidence of cardiorenal benefits. MF should be avoided in the AM phenotype due to their weight loss property. Although weight loss is not desired in AM phenotype, SGLT-2i may still be preferred with close follow-up in certain individuals demonstrating high cardiovascular disease (CVD) risk. Of note, SGLT-2i should be considered earlier in the diabetes treatment in both groups due to their multiple benefits, i.e., organ protective effects, the potential to reduce polypharmacy, and improve frailty status. The concept of different metabolic phenotypes in frail older adults with diabetes once again shows "one size fits all" cannot be applied in geriatric medicine, and a tailored, individualized approach should be adopted to get the highest benefit from treatments.