Efficacy and safety of SGLT2 inhibitors in elderly patients with type 2 diabetes.
SGLT2 inhibitors may protect kidney function in elderly diabetic patients but increase genital infection risk. Consider patient characteristics when prescribing.
Where it sits
this study against the rest of the dulaglutide corpusSummary and findings
This study evaluated the efficacy and safety of SGLT2 inhibitors in elderly patients with type 2 diabetes, focusing on renal and cardiovascular outcomes. It involved a retrospective cohort of 9,915 patients, with 1,529 matched pairs of SGLT2 inhibitor users and non-users. SGLT2 inhibitors were associated with significant renal protection but increased risk of genital infections.
Abstract
<h4>Objectives</h4>To evaluate the effectiveness and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in elderly patients with type 2 diabetes mellitus, with particular focus on renal and cardiovascular outcomes.<h4>Methods</h4>This retrospective cohort study analyzed data from 9,915 diabetic patients aged ≥65 years who received antihyperglycemic therapy at Changhua Christian Hospital, Taiwan, between January 2021 and September 2023. Patients were categorized as SGLT2 inhibitor users (<i>n</i> = 3,345) or non-users (<i>n</i> = 6,570). After 1:1 propensity score matching, 1,529 patients remained in each group. Primary outcomes included renal function (measured by eGFR decline), coronary artery disease, ischemic stroke, and heart failure. Secondary outcomes included urinary tract infection, genital infection, diabetic ketoacidosis, and hypoglycemia.<h4>Results</h4>SGLT2 inhibitor use was associated with significant renoprotective effects, demonstrated by reduced risk of 30% eGFR decline (HR 0.69, 95% CI 0.59-0.80, <i>p</i> < 0.001) and 50% eGFR decline (HR 0.60, 95% CI 0.45-0.80, <i>p</i> < 0.001). Subgroup analyses revealed that renoprotective effects were more pronounced in patients with higher baseline eGFR (≥50 mL/min/1.73 m<sup>2</sup>), suggesting greater benefit with early initiation of SGLT2 inhibitors for kidney protection. However, SGLT2 inhibitor use was associated with an increased risk of genital infections (HR 4.29, 95% CI 1.02-18.04, <i>p</i> = 0.047) in patients without prior history of such infections.<h4>Conclusions</h4>In elderly patients with type 2 diabetes, SGLT2 inhibitors demonstrate significant renal protective effects, particularly among those with preserved renal function (eGFR ≥50 mL/min/1.73 m<sup>2</sup>). These findings highlight the importance of considering patient characteristics when evaluating potential benefits of SGLT2 inhibitor therapy. The differential risk patterns suggest that clinicians should consider individual patient profiles and medical histories when prescribing these medications. The occurrence of major adverse cardiovascular events (MACE) did not exhibit a statistically significant difference between the cohort administered SGLT2 inhibitors and the cohort not receiving SGLT2 inhibitors (log-rank <i>p</i>-value = 0.160). Conversely, the recurrence of MACE was markedly reduced in the cohort receiving SGLT2 inhibitors (log-rank <i>p</i>-value < 0.001). These findings should be interpreted in the context of a single-center retrospective design and the inherent limitations of propensity-score-matched observational analyses.
Background
The study addresses the clinical question of whether SGLT2 inhibitors provide renal and cardiovascular benefits in elderly patients with type 2 diabetes. Previous research has shown potential benefits of SGLT2 inhibitors in younger populations, but data specific to the elderly are limited. This study is important as it focuses on a population that is often underrepresented in clinical trials.
Methods
This was a retrospective cohort study conducted at Changhua Christian Hospital, Taiwan, involving 9,915 diabetic patients aged 65 years and older. Patients were divided into SGLT2 inhibitor users (n=3,345) and non-users (n=6,570), with 1:1 propensity score matching resulting in 1,529 patients in each group. The primary outcomes were renal function decline, coronary artery disease, ischemic stroke, and heart failure, while secondary outcomes included infections and hypoglycemia.
Results
The study found that SGLT2 inhibitor use was associated with a reduced risk of 30% and 50% eGFR decline, with hazard ratios of 0.69 and 0.60, respectively, both statistically significant. Subgroup analysis indicated greater renal benefits in patients with higher baseline eGFR. However, there was an increased risk of genital infections, with a hazard ratio of 4.29. No significant difference was observed in the occurrence of major adverse cardiovascular events, though recurrence was reduced in the SGLT2 inhibitor group.
Interpretation
The findings suggest that SGLT2 inhibitors offer significant renal protection in elderly patients with type 2 diabetes, particularly those with preserved renal function. However, the increased risk of genital infections warrants caution. The lack of significant difference in initial MACE occurrence but reduced recurrence may indicate a nuanced cardiovascular benefit. The study's retrospective design and single-center setting limit the generalizability of the results.
Key findings
- HR 0.69 for 30% eGFR decline, 95% CI 0.59-0.80, p<0.001
- HR 0.60 for 50% eGFR decline, 95% CI 0.45-0.80, p<0.001
- HR 4.29 for genital infections, 95% CI 1.02-18.04, p=0.047
- No significant difference in MACE, log-rank p=0.160
- Reduced recurrence of MACE, log-rank p<0.001
Limitations
- Single-center study
- Retrospective design
- Propensity-score matching limitations
- Increased genital infection risk
- Observational study design