For older adults with diabetes, CV risk lower with SGLT2 or GLP-1 vs. DPP-IV therapy
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Key takeaways:
- Older adults with type 2 diabetes have better CV outcomes when receiving an SGLT2 inhibitor or GLP-1 receptor agonist vs. a DPP-IV inhibitor.
- The largest CV benefits were observed for adults with frailty.
Older adults with type 2 diabetes are less likely to have a cardiovascular event if they are initially prescribed an SGLT2 inhibitor or GLP-1 receptor agonist instead of a DPP-IV inhibitor, according to findings published in Diabetes Care.
“The initiation of an SGLT2 inhibitor or a GLP-1 receptor agonist compared with a DPP-IV inhibitor was associated with lower CV events and death without increasing the overall incidence rate of severe safety outcomes, regardless of frailty status,” Elisabetta Patorno, MD, DrPH, associate professor of medicine at Harvard Medical School and associate epidemiologist in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, and colleagues wrote. “Importantly, absolute rate reductions for all effectiveness outcomes were larger with increasing severity of frailty.”
Researchers conducted a retrospective cohort study of older adults aged at least 65 years diagnosed with type 2 diabetes who initiated an SGLT2 inhibitor, GLP-1 receptor agonist or a DPP-IV inhibitor. Data were obtained from the Medicare fee-for-service data from Parts A, B and D from April 2013 to December 2019. Three propensity-matched studies were conducted comparing each of the three drug classes. A validated claims-based frailty index was used to measure frailty. Adults with a frailty index score of less than 0.15 were considered not frail, those with a score of 0.15 to 0.24 had pre-frailty and adults with a score of 0.25 or higher were defined as having frailty. Follow-up continued until treatment discontinuation, a switch to another drug class, occurrence of a CV or safety event, death, end of health plan enrollment or the end of the study. The primary CV outcomes were time to first hospitalization for acute myocardial infarction or ischemic stroke, hospitalization for heart failure or all-cause mortality.
SGLT2s, GLP-1s outperform DPP-IV inhibitors for CV safety
There were 120,202 adults receiving SGLT2 inhibitors who were compared with 120,202 adults receiving DPP-IV inhibitors. During a mean follow-up of 10.6 months, adults receiving an SGLT2 inhibitor had a lower risk for a CV event than those receiving a DPP-IV inhibitor (HR = 0.72; 95% CI, 0.69-0.75). The CV incidence rate difference was larger among adults with pre-frailty or frailty. Those receiving an SGLT2 inhibitor were less likely to have an adverse safety event than adults receiving a DPP-IV inhibitor (HR = 0.81; 95% CI, 0.77-0.84), though the SGLT2 inhibitor group had higher rates of diabetic ketoacidosis, genital infections and lower limb amputations.
There were 113,864 matched pairs in the GLP-1 receptor agonist and DPP-IV inhibitor comparison. During a mean 10.7 months, adults receiving a GLP-1 receptor agonist had a lower risk for a CV event than those who initiated a DPP-IV inhibitor (HR = 0.74; 95% CI, 0.71-0.77). The difference in events between the two drug classes was larger among adults with pre-frailty or frailty. The GLP-1 receptor agonist group was also less likely to have an adverse safety outcome than those receiving a DPP-IV inhibitor (HR = 0.9; 95% CI, 0.87-0.94).
“We found that frailer people experienced larger benefits from SGLT2 inhibitors or GLP-1 receptor agonist treatment than those without frailty, as explicitly shown by the number needed to treat for the primary effectiveness outcome,” the researchers wrote. “Given the stable HRs across the spectrum of frailty, these differences in number needed to treat between frail and non-frail people are primarily driven by the higher number of events among frail patients, which highlights the greater vulnerability of this population.”
Lower CV risk with SGLT2 inhibitors vs. GLP-1s
The comparison between SGLT2 inhibitors and GLP-1 receptor agonists included 89,865 adults in each group. During a mean follow-up of 9.6 months, adults receiving an SGLT2 inhibitor had a lower risk for a CV event than those receiving a GLP-1 receptor agonist (HR = 0.92; 95% CI, 0.87-0.97). No difference was observed between frailty groups. Adults receiving an SGLT2 inhibitor also had a lower risk for an adverse safety outcome than the GLP-1 receptor agonist group (HR = 0.91; 95% CI, 0.86-0.95), though those receiving SGLT2 inhibitors had higher rates of DKA and genital infections.
“Compared with GLP-1 receptor agonists, initiation of SGLT2 inhibitors was associated with a rate reduction of hospitalization for heart failure, with larger benefit among frailer people on an absolute rate scale,” the researchers wrote. “Otherwise, effectiveness outcomes were comparable between the two groups.”
The researchers said future long-term CV clinical trials conducted for older adults with type 2 diabetes need to assess frailty to better establish the risk-benefit profiles of using a specific medication.
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