Comparative Effectiveness and Safety of Sodium–Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults

Jan 26, 2021Diabetes care

Effectiveness and safety of two diabetes drug types in older adults: SGLT2 inhibitors versus GLP-1 receptor agonists

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Abstract

Among 90,094 older adults with type 2 diabetes, SGLT2 inhibitors are associated with a similar risk of major adverse cardiovascular events but a reduced risk of hospitalization for heart failure compared to GLP-1 receptor agonists.

SGLT2 inhibitors showed a hazard ratio of 0.98 for major adverse cardiovascular events compared to GLP-1 receptor agonists.
SGLT2 inhibitors were associated with a 32% lower risk of hospitalization for heart failure (hazard ratio 0.68).
There were 0.7 more occurrences of diabetic ketoacidosis and 0.9 more lower-limb amputations per 1,000 person-years for SGLT2 inhibitor users.
SGLT2 inhibitor users experienced significantly more genital infections, with an increase of 57.1 cases per 1,000 person-years.
SGLT2 inhibitors resulted in 7.1 fewer acute kidney injury events compared to GLP-1 receptor agonists.

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OBJECTIVE: Both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in randomized controlled trials of patients with type 2 diabetes (T2D) generally <65 years old and mostly with cardiovascular disease. We aimed to evaluate the comparative effectiveness and safety of SGLT2i and GLP-1RA among real-world older adults.

RESEARCH DESIGN AND METHODS: Using Medicare data (April 2013-December 2016), we identified 90,094 propensity score-matched (1:1) T2D patients ≥66 years old initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE) (i.e., myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections, fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections, and overall mortality. We estimated hazard ratios (HRs) and rate differences (RDs) per 1,000 person-years, controlling for 140 baseline covariates.

RESULTS: Compared with GLP-1RA, SGLT2i initiators had similar MACE risk (HR 0.98 [95% CI 0.87, 1.10]; RD -0.38 [95% CI -2.48, 1.72]) and reduced HHF risk (HR 0.68 [95% CI 0.57, 0.80]; RD -3.23 [95% CI -4.68, -1.77]), over a median follow-up of ∼6 months. They also had 0.7 more DKA events (RD 0.72 [95% CI 0.02, 1.41]), 0.9 more LLA (RD 0.90 [95% CI 0.10, 1.70]), 57.1 more genital infections (RD 57.08 [95% CI 53.45, 60.70]), and 7.1 fewer AKI events (RD -7.05 [95% CI -10.27, -3.83]) per 1,000 person-years.

CONCLUSIONS: Among older adults, those taking SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and genital infections versus those taking GLP-1RA.

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Comparative Effectiveness and Safety of Sodium–Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults

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