medwireNews: Combination therapy with a glucagon-like peptide (GLP)-1 receptor agonist and a thiazolidinedione significantly reduces the risk for cardiovascular (CV) events and death in people with type 2 diabetes, relative to nonuse, real-world study data show.
The combination also lowered the risk for death to a greater degree than either of the individual components compared with nonuse but was associated with an increased risk for hypoglycemia, report Kuan-Cheng Chang (China Medical University Hospital, Taichung, Taiwan) and co-authors in JAMA Network Open.
They reviewed data from Taiwan’s National Health Insurance Research Database for 110,411 people with type 2 diabetes (mean age 58 years, 54.5% men) who received a GLP-1 receptor agonist (n=47,526), a thiazolidinedione (n=32,203), or both (n=30,682) between 2011 and 2020.
The participants were matched by sex, age, comorbidities, medications, Diabetes Complications Severity Index score, and diabetes duration with an equal number of people with type 2 diabetes who did not use either medication, for a total cohort size of 220,822.
The researchers report that, after adjustment for potential confounders, individuals receiving dual GLP-1 receptor agonist and thiazolidinedione therapy had significantly lower risk for all-cause mortality (hazard ratio [HR]=0.20) and CV mortality (HR=0.20) than those who did not receive either type of agent.
By comparison, the HRs for all-cause mortality and CV mortality with GLP-1 receptor agonist use versus nonuse were a significant 0.36 and 0.34, respectively, and a significant 0.55 and 0.59, respectively, with thiazolidinedione use versus nonuse. The greater risk reduction with the combination therapy “suggests a potential synergistic effect on mortality,” Chang et al remark.
In addition, participants using the combination had a significantly lower risk for major adverse CV events (MACE), defined as nonfatal myocardial infarction, nonfatal cerebrovascular disease, or CV mortality, than nonusers (HR=0.85).
For this outcome, the risk reduction was also significant with GLP-1 receptor agonist monotherapy versus no treatment (HR=0.75) but not with thiazolidinedione monotherapy.
The team also observed that people using dual GLP-1 receptor agonist and thiazolidinedione therapy had significantly lower risks than nonusers for myocardial infarction (HR=0.73), heart failure (HR=0.85), and cerebrovascular disease (HR=0.93).
By contrast, people using both medication types had a significantly higher risk for peripheral artery disease (HR=1.17), ischemic heart disease (HR=1.22), and hypoglycemia (HR=1.61) compared with those who used neither.
The risk for hypoglycemia was also significantly higher among thiazolidinedione monotherapy users than nonusers (HR=1.69) but was significantly lower with GLP-1 receptor agonist use versus nonuse (HR=0.87).
Of note, the increased risks lessened with use for more than 900 days, which Chang and co-investigators say “suggests that the longer-term cardiovascular benefits of combination therapy may outweigh the risks.”
But they add: “Further clinical studies are essential to ascertain the long-term cardiovascular benefits of this combination therapy approach.”
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