The Use of SGLT-2 Inhibitors and GLP-1RA in Frail Older People with Diabetes: A Personalised Approach Is Required.

Abstract

Background: Frailty is an increasingly recognised complication of diabetes in older people and should be taken into consideration in management plans, including the use of the new therapies of sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon like peptide-1 receptor agonists (GLP-1RA). The frailty syndrome appears to span across a spectrum, from a sarcopenic obese phenotype at one end, characterised by obesity, insulin resistance, and prevalent cardiovascular risk factors, to an anorexic malnourished phenotype at the other end, characterised by significant weight loss, reduced insulin resistance, and less prevalent cardiovascular risk factors. Therefore, the use of the new therapies may not be suitable for every frail older individual with diabetes. Objectives: To review the characteristics and phenotype of frail older people with diabetes who should benefit from the use of SGLT-2 inhibitors or GLP-1RA. Methods: A narrative review of the studies investigating the benefits of SGLT-2 inhibitors and GLP-1RA in frail older people with diabetes. Results: The current evidence is indirect, and the literature suggests that the new therapies are effective in frail older people with diabetes and the benefit appears to be proportional with the severity of frailty. However, frail patients described in the literature who benefited from such therapy appeared to be either overweight or obese, and to have a higher prevalence of unfavourable metabolism and cardiovascular risk factors such as dyslipidaemia, gout, and hypertension compared to non-frail subjects. They also have a higher prevalence of established cardiovascular disease compared with non-frail individuals. In absolute terms, their higher cardiovascular baseline risk meant that they benefited the most from such therapy. The characteristics of this group of frail patients fulfil the criteria of the sarcopenic obese frailty phenotype, which is likely to benefit most from the new therapies due to the unfavourable metabolic profile of this phenotype. There is no current evidence to suggest the benefit of the new therapies in the anorexic malnourished phenotype, which is underrepresented or totally excluded from these studies, such as in patients living in care homes. This phenotype is likely to be intolerant to such therapy due to its associated risk of inducing further weight loss, dehydration, and hypotension. Conclusions: Clinicians should consider the early use of the new therapies in frail older people with diabetes who are either of normal weight, overweight, or obese with prevalent cardiovascular risk factors, and avoid their use in those frail subjects who ae underweight, anorexic, and malnourished.