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From the Journals

Dual Therapy Lowers Death Risk in Diabetes Study

A large study found that combining GLP-1 receptor agonists with thiazolidinediones significantly reduced death and heart risks in patients with type 2 diabetes.

Conexiant

A nationwide study of more than 220,000 patients in Taiwan found that combining two diabetes drugs—glucagon-like peptide 1 receptor agonists and thiazolidinediones—was linked to a significantly lower risk of death and cardiovascular complications in people with type 2 diabetes.

In their JAMA Network Open article, the study researchers reported that patients who received both drugs had an 80% lower risk of all-cause mortality compared with those who did not receive either drug. The adjusted hazard ratio (AHR) for all-cause mortality was 0.20 (95% confidence interval [CI] = 0.19–0.21; P < .001). Cardiovascular mortality was also reduced by 80% (AHR = 0.20; 95% CI = 0.18–0.23; P < .001).

The researchers used data from Taiwan’s National Health Insurance Research Database and analyzed adults with type 2 diabetes between 2011 and 2020. They included 110,411 patients who were treated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), thiazolidinedione, or both, and matched them 1:1 with nonusers.

In addition to lower risk of all-cause mortality, patients who received combination therapy also experienced fewer major adverse cardiovascular events (MACEs), including heart attack and stroke. Compared with nonusers, their risk of MACEs was 15% lower (AHR = 0.85; 95% CI = 0.82–0.89; P < .001), and rates of heart failure and myocardial infarction were also reduced.

However, the dual therapy group had a higher risk of hypoglycemia (AHR = 1.61; 95% CI = 1.43–1.82; P < .001), especially within the first year of use. This risk declined over time. Among patients who used the therapy for more than 900 days, the AHR for all-cause mortality dropped further to 0.09 (95% CI = 0.08–0.10).

Patients who used only thiazolidinediones had a higher risk of death and cardiovascular events compared with those on GLP-1 RA monotherapy. The AHR for all-cause mortality in this group was 1.29 (95% CI = 1.24–1.34; P < .001), and 1.28 (95% CI = 1.13–1.45; P < .001) for cardiovascular mortality.

“[These findings] suggest that the longer-term cardiovascular benefits of combination therapy may outweigh the risks," wrote lead author Jing-Xing Li, MD, of the Department of Internal Medicine at China Medical University Hospital in Taichung, Taiwan, with colleagues. However, causation could not be established due to the study's observational design, and further research is needed to confirm long-term safety and determine strategies to manage early hypoglycemia risk.

No conflicts of interest were reported.