A comprehensive network meta-analysis of 601 trials revealed that sodium-glucose cotransporter 2 inhibitors provided enhanced cardiovascular protection in older adult patients with type 2 diabetes, despite showing reduced effectiveness in lowering blood glucose compared with in younger patients.
In the study, published in JAMA, investigators analyzed data from 309,503 participants across trials examining sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors. They found that while SGLT2 inhibitors' ability to lower hemoglobin A1c decreased with age, their cardioprotective benefits actually increased in older adults.
"The SGLT2 inhibitors were associated with reduced major adverse cardiovascular events in older [patients] regardless of sex," the study authors reported, noting hazard ratios (HR) of 0.84 for 75-year-old female patients and 0.81 for 75-year-old male patients compared with those who received placebo.
In contrast, GLP-1 receptor agonists showed greater blood glucose reduction with increasing age but demonstrated better cardiovascular protection in younger patients, particularly younger female patients. For GLP-1 receptor agonists, the HR for major adverse cardiovascular events was 0.85 among 55-year-old female patients.
Lead study author Peter Hanlon, PhD, of the University of Glasgow, and his colleagues noted that their findings highlighted "the limitation of surrogate outcomes (such as hemoglobin A1c) in determining the risks of major adverse cardiovascular events, for which hyperglycemia is a less important risk factor than hypertension or dyslipidemia."
The study's implications were particularly relevant given that approximately half of patients with type 2 diabetes are older than 65 years. However, the investigators emphasized that their findings were limited to the age ranges studied, since clinical trials rarely enroll patients aged older than 80 years.
The analysis included 103 trials with individual participant data and 498 trials with aggregate data. The mean age of the participants was 58.9 years for trials reporting hemoglobin A1c outcomes and 64.0 years for those reporting cardiovascular outcomes. Female patients represented 42.3% and 35.3% of participants in these respective trial groups.
The results of the study may influence treatment decisions among older adults with type 2 diabetes, suggesting that the cardiovascular benefits of SGLT2 inhibitors should be considered alongside their glycemic effects.
"Current clinical guidelines recommend less stringent glycemic targets in older [patients] living with multiple long-term conditions or frailty [as a result of the] greater risks of adverse events. The current findings highlighted the need to consider the cardioprotective effects of therapies when treating older [patients] in addition to safety, tolerability, and the priorities of patients," the investigators concluded.
The study was funded by the Medical Research Council and utilized data from multiple pharmaceutical companies through the Yale University Open Data Access Project and Vivli Inc. Full disclosures can be found in the study.