Criteria of frail older people with type 2 diabetes who are suitable for SGLT-2 inhibitors and GLP-1RA therapy.

Frailty is a metabolically heterogeneous condition and therefore, frail older people with diabetes are metabolically diverse. Diversity is caused by the varying degrees of insulin resistance, determined by the variability in muscle mass/visceral fat ratio and the overall body weight. This creates a frailty spectrum with sarcopenic/obese at one end to malnourished anorexic individuals at the other end. The sarcopenic obese are likely to have increased insulin resistance and progression of the metabolic syndrome. On the other hand, the anorexic malnourished are likely to have decreased insulin resistance due to significant weight loss and regression of the metabolic syndrome. The current evidence showed benefits of SGLT-2 inhibitors and GLP-1RA in frail older people with diabetes, and these benefits increased with increasing frailty. However, the majority of the population who benefited from this therapy were either overweight or obese. There is no evidence of benefits of such therapy in the anorexic malnourished end of the frailty spectrum such as people residents in care homes who were likely excluded from clinical trials. As the sarcopenic obese frail individuals are likely to have high burden of atherosclerotic vascular disease, we suggest that triple therapy of metformin, SGLT-2 inhibitors and GLP-1RA to be initiated as first line therapy in this group of patients if tolerated. On the other hand, this therapy is better avoided in the malnourished frail individuals due to significant weight loss, high risk of adverse events and, due to regression of the metabolic syndrome, the cardiovascular benefits are uncertain.