SGLT2 inhibitors may offer more cardioprotective benefits than GLP-1s for older adults
Key takeaways:
- GLP-1 receptor agonists conferred greater HbA1c reductions in older adults than younger adults.
- Older adults had a lower risk for major adverse CV events than younger adults with SGLT2 inhibitors.
SGLT2 inhibitors confer greater risk reductions for major adverse cardiovascular events in older adults with type 2 diabetes compared with younger adults, according to findings from a systematic review and meta-analysis published in JAMA.
Researchers obtained data from 601 randomized controlled trials enrolling adults with type 2 diabetes and assessing the efficacy of SGLT2 inhibitors, GLP-1s or DPP-IV inhibitors on HbA1c or major adverse CV events. Older adults had a lower risk for major adverse CV events when using an SGLT2 inhibitor than younger adults. This is despite older adults having a greater decline in HbA1c with GLP-1 use than younger adults.
“Age should not be a barrier to treatment with SGLT2 inhibitors in patients who are likely to benefit from reduced CV risk,” Peter Hanlon, PhD, clinical senior research fellow in the School of Health and Wellbeing at University of Glasgow in the U.K., told Healio. “It also suggests that for these treatments that have a proven CV benefit, change in blood glucose may be a poor indicator of the protective effect on CV outcomes.”
Researchers searched for randomized controlled trials conducted through November 2022 in the MEDLINE and Embase databases, and in U.S. and China clinical trial registries. There were 592 trials enrolling 309,503 participants that reported on HbA1c outcomes and 23 trials enrolling 168,489 participants reporting on major adverse CV events. The differences in efficacy by age were disseminated in 30-year increments.
Treatment with any class of therapy was associated with an HbA1c reduction of 0.5 to 1.5 percentage points compared with placebo. SGLT2 inhibitors and GLP-1s, but not DPP-IV inhibitors, lowered the risk for major adverse CV events vs. placebo.
Older adults had less of an HbA1c reduction with SGLT2 inhibitor monotherapy, dual therapy or triple therapy than younger adults, whereas older age was associated with a greater HbA1c decrease with GLP-1 monotherapy and dual therapy. Dual therapy with a DPP-IV inhibitor was tied with a greater HbA1c reduction for older adults vs. younger adults.
Older adults receiving an SGLT2 inhibitor had a 24% reduction in major adverse CV events compared with younger adults (HR = 0.76; 95% CI, 0.62-0.93). Conversely, GLP-1s conferred a 47% higher risk for major adverse CV events in older adults vs. younger adults (HR = 1.47; 95% CI, 1.07-2.02).
“We were surprised that even though the CV benefits of SGLT2 inhibitors were greater in older people, the reduction in blood glucose was less in older compared to younger people,” Hanlon said.
The risk for major adverse CV events with SGLT2 inhibitor or GLP-1 therapy did not differ between men and women. Men had a higher risk for major adverse CV events with DPP-IV inhibitor use compared with women (HR = 1.65; 95% CI, 1.25-2.21).
“The trials included in our meta-analysis included very few participants older than 80 years,” Hanlon said. “They also did not measure things like frailty, which can have important implications for treatment priorities and risks in older people. We need more evidence to guide our treatment of people in much older age and who are living with frailty.”
For more information:
Peter Hanlon, PhD, can be reached at peter.hanlon@glasgow.ac.uk.
Perspective
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At present, medical management of type 2 diabetes hinges on the presence of other comorbidities, particularly atherosclerotic cardiovascular disease, heart failure, chronic kidney disease and obesity. Whether other evident factors, such as age or sex, could be used to guide treatment or predict treatment outcomes is not clear.
This study by Hanlon and colleagues identified primarily age-related heterogeneity in the effects of SGLT2 inhibitors and GLP-1s on glycemic control and major adverse cardiovascular events, with SGLT2s having decreasing glycemic effects but increasing CV benefit in older adults, and GLP-1s demonstrating the opposite pattern.
As most trials either exclude or enroll very few individuals over 75 to 80 years of age, little is known about medication efficacy and safety in this group. However, older adults are also the population with the greatest absolute risk for CVD who may therefore receive the greatest population-level benefit from these medications, and studies demonstrate that rates of SGLT2 and GLP-1 use are lower in older populations.
Findings of this study help to understand the effects of these medications in older populations, providing reassurance as to both the efficacy and safety of these medications and suggesting opportunities for further research to determine whether these findings could guide medication selection for older adults with type 2 diabetes.
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