BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to improve renal and cardiovascular outcomes in patients with type 2 diabetes. Limited evidence exists about the efficacy and safety of SGLT2 inhibitors in patients with frailty.
METHODS: This was a post hoc pooled, participant-level data analysis of the CANVAS Program (CANVAS and CANVAS-R) and the CREDENCE trial. We examined the effect of canagliflozin on: (1) Major adverse cardiovascular events (MACE), (2) Cardiovascular mortality, (3) all-cause mortality, and (4) key safety outcomes. Frailty was defined by a Frailty Index (FI) based on a deficit accumulation approach (FI > 0.25: frail). Cox proportional-hazard models were used to estimate the efficacy and safety of canagliflozin overall and according to frailty status.
RESULTS: There were 14,543 participants (10,142 from the CANVAS Program, 4401 from the CREDENCE trial). Their mean age was 63.2 years; 35.3% were female. Frailty was present in 56% of the study participants. The benefits of canagliflozin were observed in both the frail and non-frail subgroups: HRs for MACE 0.80 (95% CI 0.70-0.90) in the frail versus 0.91 (95% CI 0.75-1.09) in the non-frail (p for interaction = 0.27); HRs for cardiovascular mortality 0.79 (95% CI 0.67-0.95) in the frail versus 0.94 (95% CI 0.70-1.27) in the non-frail (p for interaction = 0.38); HRs for all-cause mortality 0.81 (95% CI 0.70-0.94) in the frail versus 0.93 (95% CI 0.74-1.16) in the non-frail (p for interaction = 0.39). Adverse events were similar among frail and non-frail participants, except for osmotic diuresis (HRs 1.67, 95% CI 1.22-2.28 in the frail vs. 3.05, 95% CI 2.13-4.35 in the non-frail, p for interaction = 0.01).
CONCLUSIONS: Canagliflozin improved cardiovascular and mortality endpoints in participants with type 2 diabetes irrespective of frailty status, with a similar safety profile. Our findings, in addition to those from other recent studies, provide evidence to support the introduction of SGLT2 inhibitor therapy in patients perceived to be frail.
TRIAL REGISTRATION: ClinicalTrials.gov CANVAS: NCT01032629; CANVAS-R: NCT01989754; CREDENCE: NCT02065791.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Geriatrics | |
| Cardiology | |
| Endocrine | |
Another beneficial effect of SGLT-2Ri, a phlorizin derivative. Although there is some information in the current literature about the increased risk for fracture in patients who are taking canagliflozin (specifically during the first 12 weeks), no strong evidence or pathogenesis has been found about increased risk for fracture.
As a GP, the majority of my frail patients are well beyond the mean age of 63.2 years. I wonder why only the percentage over or under 65 years is given in the baseline data.
This isn't the first publication to find a positive risk/benefit profile for SGLT2i in the frail/elderly. Finding it with CANVAS/CREDENCE provides more credence (ha!) to the idea that this is real. As a primary care physician, I would continue to discuss the risks associated with these meds and recommend them to frail patients just as I would to more robust patients.
This article provides an interesting evaluation of the impact of frailty on efficacy and safety outcomes for canaglifozin. However, the bespoke frailty index (which primarily incorporates cardiovascular risk factors) limits the generalizability of these findings. Specifically, it reduces the ability to apply these findings to individuals who are typically considered frail, including those with functional or cognitive decline.
As the number of elderly patients increases, so does the number of frail elderly. As stated in this paper, SGLT2 inhibitors have revolutionized the treatment of diabetes, but their use in frail persons with diabetes was not studied. This article showed that canagliflozin in frail persons with diabetes tolerated and had beneficial effects.
