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A new study shows that tirzepatide not only outperforms semaglutide in reducing diabetes risk, but also provides enhanced protection against major cardiovascular events, setting a new standard for obesity treatment.
In a cohort study published in the journal Clinical Medicine, Researchers compared the effects of tirzepatide and semaglutide on the incidence of type 2 diabetes (T2D) and major adverse cardiovascular (CV) events in obese people (with and without pre-existing type 2 diabetes). Researchers found that compared with semaglutide, tirzepatide was associated with a lower risk of incident T2D and greater weight loss in people without T2D, and a lower risk of major adverse CV events in people with pre-existing type 2 diabetes.
background
Obesity is a major global health issue affecting over 650 million adults and over 340 million children and adolescents. Obesity is a major risk factor for type 2 diabetes, leading to increased morbidity, mortality, and significant economic costs. Management of obesity involves a combination of behavioral, dietary, pharmacological, and surgical interventions, with surgery providing the most effective weight loss but associated with risks and access barriers.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, are increasingly being used to manage obesity by suppressing appetite and slowing gastric emptying. Semaglutide has shown more pronounced weight loss compared with previous GLP-1 RAs. Tirzepatide, a new dual agonist of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), has shown even greater weight loss and may be important for reducing T2D risk and improving health outcomes in patients with obesity or T2D. However, the effect of tirzepatide on T2D incidence and CV outcomes remains unclear. Although concerns about a potential association between semaglutide and suicidal ideation have been denied, the risk of suicidal ideation with tirzepatide has not been studied. Therefore, in this study, researchers used electronic medical records (EMRs) to compare the effects of tirzepatide and semaglutide on new-onset T2D in obese patients and to study the impact on morbidity and mortality in patients with existing T2D.
About the Research
In this cohort study, we obtained de-identified EMR data from the TriNetX database. The analysis included two cohorts: individuals without pre-existing T2D and individuals with T2D. In the non-T2D cohort, participants were matched and compared after 6 months of treatment with tirzepatide (cohort 1a, n = 6923) or semaglutide (cohort 2a, 6923) and were assessed for the incidence of T2D and changes in glycosylated hemoglobin (HbA1c), weight, hypoglycemia, and acute pancreatitis over 12 months of follow-up. In both groups, participants had a mean age of 47.5 years, 73% were female, and 73-74% were white. The mean follow-up duration for the two groups was 302 and 312 days, respectively.
The T2D cohort was similarly divided into cohort 1b (n = 4223) of T2D + tirzepatide and cohort 2b (n = 4223) of T2D + semaglutide. In both groups, participants had a mean age of 53.9-54 years, 60% were female, and 68-69% were white. The mean follow-up durations for the two groups were 328 and 339 days, respectively. Matching and follow-up were similarly performed to assess time to composite CV adverse events, including mortality, cerebral infarction, coronary syndrome, heart failure, and incidence of microvascular complications and suicidal ideation. This study aimed to establish the temporal relationship between drug exposure and outcomes while controlling for potential confounders. Statistical methods used in this study included propensity score matching (PSM) with logistic regression, univariate survival analysis with hazard ratios (HR), log-rank test, Kaplan-Meier survival curves, and sensitivity analysis.
Results and Discussion
In people without type 2 diabetes, tirzepatide was found to significantly reduce the risk of developing type 2 diabetes, and weight loss and HbA1c reductions over one year were greater in the tirzepatide group compared with semaglutide (p<0.001).
In patients with type 2 diabetes, tirzepatide was found to reduce the risk of the composite outcome of mortality and cardiovascular events, particularly all-cause mortality and cerebral infarction, but was associated with an increased incidence of diabetic neuropathy. No significant differences were found between groups in the incidence of hypoglycemia, acute pancreatitis, or suicidal ideation.
This is the first real-world study to provide a large-scale comparative analysis of tirzepatide, a novel GLP1/GIP dual agonist, and semaglutide, a potent and well-established GLP1-RA. However, this study has limitations, including its observational nature, nonrandomized comparison, potential data incompleteness, lack of dosing information, and short follow-up period.
Conclusion
In conclusion, this real-world study found that compared with semaglutide, tirzepatide significantly reduced the risk of developing type 2 diabetes and major cardiovascular events in patients with obesity and type 2 diabetes. This finding suggests that tirzepatide may be a more effective treatment option in managing obesity-related health risks and preventing complications in these populations. Further randomized controlled trials are needed to confirm these results and explore the efficacy of dual incretin agonists in preventing type 2 diabetes and cardiovascular disease in high-risk populations.
Journal References:
- Incidence of new-onset type 2 diabetes in obese adults treated with tirzepatide or semaglutide: real-world evidence from an international retrospective cohort study. Matthew Anson et al. Clinical Medicine75:102777 (2024), DOI: 10.1016/j.eclinm.2024.102777, https://www.sciencedirect.com/science/article/pii/S2589537024003560