GLP-1 and thiazolidinediones may reduce cardiac risk for T2D

Top Line:

In patients with type 2 diabetes (T2D), combination therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RAS) and thiazolidinedione was associated with reduced risk of all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE) compared to those using any of these therapies.

Methodology:

• For people with T2D, the potential benefits of combination therapy with GLP-1 RAS revitalize interest in thiazolidinediones, particularly pioglitazone, despite early cardiovascular safety concerns of rosiglitazone, which limits use.
• The researchers conducted a retrospective cohort study using national health insurance data from Taiwan (2011-2020) to examine the effects of combination therapy with GLP-1 RAS (exenatide, lixisenatide, duraglutide, or liraglutide, or thiazolidate madion (people who received rosiglitazone or pioglitazone) on diabetic complications.
• The cohort included 110,411 patients with T2D (mean age, 58 years, 45% of women) who received one or both medications. They had a propensity score consistent with 110,411 patients who did not use either medication.
• Key results include all-cause mortality, Maces (fatal myocardial infarction composites) [MI]Nonfatal cerebrovascular disease [CVD]and cardiovascular mortality), and cardiovascular mortality (MI, CVD, ischemic heart disease, heart failure combined [HF] and peripheral arterial disease). Secondary outcomes included individual outcomes and hypoglycemia.
• Patients continued from the first day of either medication to death, the occurrence of the outcome, or the end of the study.

remove:

• Compared with patients who did not use either drug, patients receiving GLP-1 RAS and thiazolidinedione combination therapy had a lower risk of all-cause mortality (adjusted hazard ratio) [aHR]0.20), Maces (AHR, 0.85), and cardiovascular mortality (AHR, 0.20; p <.001All). The benefits were more pronounced among those treated for more than 900 days.
• A lower risk of secondary outcomes was also seen in combination therapy compared to those who were not taking either drug – MI (AHR, 0.73; p <.001), CVD (AHR, 0.93; p = .002), and heart failure (AHR, 0.85; p <.001).
• However, the risk of hypoglycemia was higher in patients who used thiazolidinedione monotherapy (AHR, 1.69; p <.001) or combination therapy (AHR, 1.61; p <.001) More than those who did not use either drug. These risks were reduced after more than 900 days of use.
• Patients who used thiazolidinedione monotherapy had a higher risk of all-cause mortality and cardiovascular mortality than patients who used GLP-1 RA monotherapy (p for both <.001).

actually:

“This finding suggests a potential synergistic effect on mortality,” the study author wrote. “The benefits of thiazolidinediones are alleviated by associated risks, such as liquid maintenance and increased risk of HF. This study showed that GLP-1 Ras can reduce the risk of HF associated with the use of thiazolidiniones,” they added.

“[This study]along with other emerging evidence and recommendations from practice guidelines, may provide a new frontier to consider the value of cost-effective combination therapy of thiazolidinedione and GLP-1 RA in T2D patients.” Invited commentary I wrote it.

sauce:

This study was led by Jing-Xing Li, MD, MS, MS and MS of China Medical University Hospital, Taiwan. it was It's published online in Jama Network Open.

limit:

The observational design of this study limits our ability to establish causal relationships, and the results may have been influenced by residual confounding. Elderly study populations may limit the generalizability of results to younger people or to people with different baseline characteristics. The increased risk of hypoglycemia observed with combination therapy can be of great concern.

Disclosure:

This study was supported in part by grants from the Taiwan Health and Welfare Clinical Trials Center and the Chinese Medical University Hospital Clinical Trials Center. The author reported no conflict of interest.

This article was created using several editing tools, including AI as part of the process. Human Editors reviewed this content prior to its release.