Among patients with type 2 diabetes, the effect of frailty on the cardiovascular effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon- like peptide 1 receptor agonists (GLP-1 RA) is less investigated. In light of this, Kutz and colleagues assessed the cardiovascular effectiveness of SGLT-2i, GLP-1 RA, and dipeptidyl peptidase 4 inhibitors (DPP-4i) in older adults with type 2 diabetes across different strata of frailty.

The study was comparative in nature and sourced the Medicare claims data. From the data, 3 pairwise study cohorts of older patients with type 2 diabetes initiated with SGLT-2i, a GLP-1 RA, or a DPP-4i were identified. These were then categorized as per the three levels of frailty using a validated claims-based frailty index (non-frail, <0.15; pre-frail, 0.15-0.24; frail, ≥0.25).

A composite of major adverse cardiovascular events (MACE) including acute myocardial infarction, ischemic stroke, hospitalization for heart failure, and all-cause mortality was considered as the primary outcome. During the 9-months mean follow-up period, the HR for MACE associated with SGLT-2i vs. DPP-4i (overall, n=91`141 PS-matched pairs; mean age 72.1 years) was 0.82 (95% CI 0.72 to 0.93) in frail, 0.71 (0.67 to 0.75) in pre-frail, and 0.78 (0.71 to 0.86) in non-frail people (p for homogeneity = 0.033). The HR for MACE associated with GLP-1 RA vs. DPP-4i (n=90`988 pairs; age 71.8 years) was 0.84 (0.76 to 0.93) in frail, 0.77 (0.73 to 0.81) in pre-frail, and 0.82 (0.74 to 0.91) in non-frail people (p for homogeneity = 0.150). The HR for MACE associated with SGLT-2i vs. GLP-1 RA (n=67`067 pairs; age 71.7 years) was 0.87 (0.75 to 1.01) in frail, 0.93 (0.87 to 1.01) in pre- frail, and 0.90 (0.79 to 1.03) in non-frail people (p for homogeneity = 0.692). SGLT2i or GLP-1 RA had the largest absolute benefit in frail people as compared to DPP4i.

It can be elucidated from this study SGLT-2i and GLP-1 RA are associated with similar relative risk reductions in MACE among people with and without frailty with largest absolute benefits in frail people. In addition, there was a similar risk of MACE in patients initiating SGLT-2i vs. GLP-1 RA, irrespective of their frailty level.