A new study has revealed that tirzepatide, a dual incretin agonist, surpasses semaglutide in lowering the risk of type 2 diabetes (T2D) and reducing cardiovascular (CV) events among patients with obesity, establishing a new benchmark in obesity treatment.
Study Overview
The retrospective cohort study, published in eClinicalMedicine, compared tirzepatide and semaglutide’s effects on T2D incidence and major adverse cardiovascular events (MACE) in obese individuals, both with and without pre-existing T2D. The research found that tirzepatide not only led to more substantial weight loss in those without T2D but also provided greater protection against severe CV outcomes in those already diagnosed with T2D.
Background
Obesity is a global health crisis, impacting over 650 million adults and 340 million children worldwide. It significantly elevates the risk of developing T2D, leading to increased morbidity, mortality, and economic burden. Managing obesity typically involves a multifaceted approach, including lifestyle changes, medication, and sometimes surgery—the latter being the most effective but also the most invasive and least accessible.
According to the World Health Organization (WHO), diabetes affects approximately 422 million people globally, with the majority living in low- and middle-income countries. Each year, diabetes is directly responsible for 1.5 million deaths.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide have become a cornerstone in obesity management due to their ability to curb appetite and slow gastric emptying. Semaglutide, in particular, has shown significant weight loss benefits. Tirzepatide, a newer dual agonist that targets both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), has demonstrated even greater weight loss, which is vital for reducing T2D risk and improving health outcomes in obese patients. However, the full extent of tirzepatide’s impact on T2D incidence and CV outcomes had remained unclear until this study. Notably, while the potential for semaglutide to induce suicidal thoughts has been ruled out, the risk associated with tirzepatide remains unexplored.
Study Details
Researchers utilized anonymized electronic medical records (EMR) from the TriNetX database to conduct the analysis, focusing on two distinct cohorts: one group without pre-existing T2D and another with T2D. Participants in the non-T2D cohort were matched based on baseline characteristics and followed for 12 months after receiving either tirzepatide or semaglutide. This cohort included 6,923 participants in each treatment arm, with a mean follow-up period of approximately 10 months. The average age of participants was 47.5 years, with women comprising 73% of the group, and 73-74% of participants were White.
In the T2D cohort, the analysis included 4,223 participants in each treatment group. These participants were slightly older, with an average age of around 54 years, and a higher prevalence of male participants compared to the non-T2D cohort. The follow-up period was similar, averaging around 11 months. Researchers evaluated the occurrence of composite CV events, mortality, microvascular complications, and any incidences of suicidal ideation.
The study employed robust statistical methods, including propensity score matching, hazard ratio analysis, and Kaplan-Meier survival curves, to control for confounding factors and assess the temporal relationship between drug exposure and outcomes.
Key Findings
The study revealed that tirzepatide was associated with a significantly lower risk of developing T2D in individuals without the condition, alongside greater reductions in body weight and HbA1c levels over the study period.
For individuals with pre-existing T2D, tirzepatide notably reduced the risk of mortality and cerebral infarction compared to semaglutide. However, tirzepatide use was linked to a higher incidence of diabetic neuropathy. No significant differences were observed between the groups regarding hypoglycemia, acute pancreatitis, or suicidal ideation.
Study Limitations
This study is the first large-scale, real-world comparison between tirzepatide and semaglutide. However, its observational design, non-randomized comparisons, potential data gaps, lack of dosage information, and relatively short follow-up period limit the conclusiveness of the findings.
Conclusion
The findings suggest that tirzepatide may offer superior protection against T2D and CV events in obese individuals, particularly those already managing T2D, compared to semaglutide. These results highlight tirzepatide’s potential as a more effective therapeutic option in reducing obesity-related health risks. However, further randomized controlled trials are necessary to confirm these findings and explore the broader implications of dual incretin agonists in high-risk populations.
Related topics:
Cutting Nighttime Light: A Simple Strategy to Lower Diabetes Risk
60% of Africans with Diabetes Unaware of Their Condition
FDA Approves First Automated Insulin Delivery System for Type 2 Diabetes
