Comparative Cardiovascular Effectiveness and Safety of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors According to Frailty in Type 2 Diabetes

Sep 7, 2023Diabetes care

Heart benefits and safety of three diabetes drugs in frail and non-frail type 2 diabetes patients

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Abstract

The overall hazard ratio for cardiovascular effectiveness associated with SGLT-2 inhibitors was 0.72 compared to dipeptidyl peptidase 4 inhibitors.

SGLT-2 inhibitors showed a significant reduction in the risk of cardiovascular events compared to DPP-4 inhibitors, with an incidence rate difference of -13.35.
The benefits of SGLT-2 inhibitors varied by frailty level, with a larger reduction in frail individuals (-27.24) compared to nonfrail individuals (-6.74).
Glucagon-like peptide 1 receptor agonists also demonstrated effectiveness over DPP-4 inhibitors, with an overall hazard ratio of 0.74 and an incidence rate difference of -15.49.
Similar to SGLT-2 inhibitors, GLP-1 receptor agonists showed greater benefits in frail individuals compared to nonfrail, with an incidence rate difference of -25.88 in the highest frailty stratum.
Severe adverse events were not more common with either SGLT-2 inhibitors or GLP-1 receptor agonists than with DPP-4 inhibitors.

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OBJECTIVE: To evaluate the comparative cardiovascular effectiveness and safety of sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is) in older adults with type 2 diabetes (T2D) across different frailty strata.

RESEARCH DESIGN AND METHODS: We performed three 1:1 propensity score-matched cohort studies, each stratified by three frailty strata, using data from Medicare beneficiaries (2013-2019) with T2D who initiated SGLT-2is, GLP-1RAs, or DPP-4is. In time-to-event analyses, we assessed the primary cardiovascular effectiveness composite outcome of acute myocardial infarction, ischemic stroke, hospitalization for heart failure, and all-cause mortality. The primary safety outcome was a composite of severe adverse events that have been linked to SGLT-2i or GLP-1RA use.

RESULTS: Compared with DPP-4is, the overall hazard ratio (HR) for the primary effectiveness outcome associated with SGLT-2is (n = 120,202 matched pairs) was 0.72 (95% CI 0.69-0.75), corresponding to an incidence rate difference (IRD) of -13.35 (95% CI -15.06 to -11.64). IRD ranged from -6.74 (95% CI -8.61 to -4.87) in nonfrail to -27.24 (95% CI -41.64 to -12.84) in frail people (P for interaction < 0.01). Consistent benefits were observed for GLP-1RAs compared with DPP-4is (n = 113,864), with an overall HR of 0.74 (95% CI 0.71-0.77) and an IRD of -15.49 (95% CI -17.46 to -13.52). IRD in the lowest frailty stratum was -7.02 (95% CI -9.23 to -4.81) and -25.88 (95% CI -38.30 to -13.46) in the highest (P for interaction < 0.01). Results for SGLT-2is versus GLP-1RAs (n = 89,865) were comparable. Severe adverse events were not more frequent with SGLT-2is or GLP-1RAs than DPP-4is.

CONCLUSIONS: SGLT-2is and GLP-1RAs safely improved cardiovascular outcomes and all-cause mortality, with the largest absolute benefits among frail people.

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Comparative Cardiovascular Effectiveness and Safety of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors According to Frailty in Type 2 Diabetes

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