REGISTRO DOI: 10.69849/revistaft/ra10202508151353
Bianca Lunna Pereira da Silva Costa Barros1;Leandro Cardozo Batista2; Lucas Saboia Marinho3; Felipe Santos Teixeira Martiniano4; John Wesley Nascimento Veloso5; Daiana Nascimento Veloso6; Cristiano Oliveira Nascimento Costa7; Jhulyani Neves da Silva8; Carolina Carvalho de Freitas9; Maria Clara Guimarães Costa10
Abstract
Introduction: The increasing prevalence of type 2 diabetes and obesity highlights the need for therapies that address both glycemic control and weight reduction. Tirzepatide, a dual GIP and GLP-1 receptor agonist, has shown superior results compared to semaglutide and insulin glargine. Imaging techniques provide objective evidence of its structural and functional benefits.
Objective: To compare the efficacy of tirzepatide with semaglutide and insulin glargine in glycemic control, weight loss, and imaging-based clinical outcomes in adults with type 2 diabetes and/or obesity. Method: An integrative literature review was performed in PubMed (July 2025) using the terms “tirzepatide”, “semaglutide”, “insulin glargine”, “type 2 diabetes”, “obesity”, “MRI”, “echocardiography”, “body composition”, and “imaging”. Inclusion criteria were randomized clinical trials or comparative studies (2022–2025) involving adults with type 2 diabetes and/or obesity, comparing tirzepatide with semaglutide and/or insulin glargine, and applying imaging methods to assess outcomes. Ten studies met the criteria after screening. Results: Tirzepatide achieved greater HbA1c and weight reductions than semaglutide and insulin glargine. Imaging studies showed reductions in intramuscular, visceral, and epicardial fat, preservation of lean mass, and improved diastolic function in HFpEF patients. Additional outcomes included improved quality of life, sustained weight loss, favorable cost-effectiveness, and consistent efficacy across age groups. No significant association was found with suicidal ideation, though a higher incidence of biliary events was observed without increased pancreatitis risk. Conclusion: Tirzepatide offers superior metabolic and structural benefits supported by imaging evidence, making it a comprehensive therapeutic option for managing type 2 diabetes and obesity.
Keywords: tirzepatide; semaglutide; insulin glargine; type 2 diabetes; obesity; imaging; MRI; echocardiography; body composition; cardiovascular risk.
Introduction
The rising prevalence of type 2 diabetes and obesity poses an increasing challenge to global public health, demanding therapeutic strategies that act in an integrated manner to improve glycemic control, promote weight reduction, and prevent associated complications (Huang et al., 2025). In recent years, dual agonists of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors have emerged as promising alternatives, with tirzepatide standing out for offering superior benefits compared to established therapies such as semaglutide and insulin glargine (Ali et al., 2025).
In addition to traditional laboratory endpoints, the incorporation of advanced imaging methods has expanded the understanding of how these therapies affect the body (Liao et al., 2025). Techniques such as magnetic resonance imaging, computed tomography, and echocardiography enable precise and noninvasive assessment of changes in body composition, cardiac function, and visceral fat distribution (Gao et al., 2025; Fang et al., 2025; Jiang et al., 2025). These data complement biochemical markers, providing a more comprehensive view of the metabolic and cardiovascular impact of pharmacological interventions (American Diabetes Association, 2024).
Recent studies have shown that imaging assessment can reveal additional benefits of tirzepatide, such as the preservation of lean mass, selective reduction of intramuscular fat, and improvements in structural and functional cardiac parameters (Sattar et al., 2025; Kramer et al., 2024). These findings reinforce the importance of integrating objective measures obtained from imaging exams into clinical follow-up, especially in patients with multiple metabolic and cardiovascular comorbidities (Look et al., 2025).
Therefore, understanding tirzepatide’s role not only as a glucose-lowering and weight-reducing agent but also as a modulator of structural parameters detectable by imaging is essential for optimizing therapeutic strategies and promoting a more personalized and effective approach to the management of type 2 diabetes and obesity. This study aims to evaluate the efficacy of tirzepatide compared with semaglutide and insulin glargine in glycemic control, weight reduction, and clinical outcomes assessed by imaging methods, such as magnetic resonance imaging and echocardiography, in individuals with type 2 diabetes and/or obesity.
Method
An integrative literature review was conducted in accordance with methodological guidelines for clinical reviews. The search was performed in the PubMed database in July 2025 using the following descriptors combined with Boolean operators: “tirzepatide”, “semaglutide”, “insulin glargine”, “type 2 diabetes”, “obesity”, “MRI”, “echocardiography”, “body composition”, and “imaging”.
A total of 305 articles were initially identified. The selection process followed three steps:
- Screening by title and abstract to exclude studies not related to the topic;
- Full-text reading to confirm eligibility;
- Application of inclusion and exclusion criteria.
The Inclusion criteria were: randomized clinical trials or comparative studies published between 2022 and 2025; adult participants diagnosed with type 2 diabetes and/or obesity; comparison between tirzepatide, semaglutide, and/or insulin glargine; use of imaging methods (magnetic resonance imaging, computed tomography, echocardiography, or ultrasound) to assess structural or functional outcomes.
The exclusion criteria were: animal studies; narrative reviews or opinion articles; duplicate publications; studies without full-text access.
After applying these criteria, 10 studies were included in the final analysis. Data extracted from each article included year of publication, study population, intervention, comparator, imaging method used, and main clinical outcomes. The synthesis of results was conducted descriptively, highlighting convergent and divergent findings among the studies.
Results
Table 1 – Summary of studies included in the review
| Year | Authors | Title | Objective | Main Outcome |
| 2025 | Sattar et al. | Tirzepatide and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis. | To assess the impact of tirzepatide on muscle composition using MRI. | Tirzepatide improves muscle composition by reducing fat without compromising lean tissue. |
| 2025 | Lin et al. | Effectiveness of tirzepatide in patients with HFpEF using a target trial emulation retrospective cohort study. | To evaluate the effects of tirzepatide in patients with heart failure with preserved ejection fraction (HFpEF). | Tirzepatide provides functional cardiac benefits in HFpEF patients. |
| 2025 | Hankosky et al. | Tirzepatide 10 and 15 mg versus semaglutide 2.4 mg in people with obesity or overweight with type 2 diabetes: An indirect treatment comparison. | To compare the efficacy of tirzepatide versus semaglutide in weight loss and glycemic control. | HbA1c 0.56% lower and weight loss up to 4.79% greater with tirzepatide. Tirzepatide outperforms semaglutide in glycemic control and weight reduction. |
| 2025 | Garvey et al. | Tirzepatide and visceral and epicardial fat reduction in patients at cardiovascular risk. | To assess tirzepatide’s effects on visceral and epicardial fat. | Significant reduction in visceral and epicardial fat measured by imaging. Tirzepatide reduces fat deposits associated with cardiovascular risk. |
| 2025 | Gibble et al. | Tirzepatide and health-related quality of life in adults with obesity or overweight: Results from the SURMOUNT-3 phase 3 randomized trial. | To investigate the effect of tirzepatide on quality of life in obesity/overweight. | Significant improvement in self-reported quality of life. Tirzepatide positively impacts subjective health parameters. |
| 2025 | Liu et al. | Tirzepatide vs semaglutide and liraglutide for weight loss in patients without diabetes: A short-term cost-effectiveness analysis. | To evaluate tirzepatide’s cost-effectiveness compared with other GLP-1 receptor agonists. | Superior cost-effectiveness and greater QALYs with tirzepatide. Tirzepatide is economically more advantageous in the short term. |
| 2025 | Ishimura et al. | Effects of patient age on the therapeutic effects of GIP/GLP-1 receptor agonists (tirzepatide). | To determine whether age influences tirzepatide’s therapeutic effects. | Consistent effects across different age groups. Tirzepatide’s efficacy is not significantly affected by age. |
| 2025 | Di Stefano et al. | GLP-1 receptor agonists, dual GIP/GLP-1 receptor agonist tirzepatide and suicidal ideation and behavior: A systematic review. | To evaluate the association between tirzepatide and suicidal ideation/behavior. | No evidence of increased risk of suicidal ideation with tirzepatide. |
| 2024 | Aronne et al. | Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4. | To evaluate long-term weight loss maintenance with tirzepatide. | Weight maintenance for 72 weeks; high treatment adherence. Tirzepatide is effective for long-term weight reduction maintenance. |
| 2023 | Zeng et al. | Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease): A meta-analysis. | To assess tirzepatide’s safety regarding biliary events and pancreatitis. | Higher incidence of biliary events; no increase in pancreatitis. Tirzepatide is safe but requires monitoring for biliary events. |
Discussion
Efficacy of Tirzepatide in Glycemic Control and Weight Reduction
The present review confirms that tirzepatide consistently outperforms other established therapies, such as semaglutide and insulin glargine, in achieving glycemic control and promoting weight loss. Comparative analyses demonstrate a greater reduction in HbA1c and body weight with tirzepatide, as evidenced by Hankosky et al. (2025), who reported a 0.56% lower HbA1c and up to 4.79% greater weight loss compared with semaglutide. These findings are supported by Aronne et al. (2024), who observed sustained weight reduction over 72 weeks, and Liu et al. (2025), who highlighted tirzepatide’s superior cost-effectiveness in weight loss compared with semaglutide and liraglutide. Importantly, Garvey et al. (2025) reported reductions in visceral and epicardial fat alongside weight loss, while Sattar et al. (2025) demonstrated improvements in muscle composition through selective fat reduction. Consistent benefits across different age groups, as shown by Ishimura et al. (2025), reinforce tirzepatide’s broad applicability. Collectively, these results emphasize tirzepatide’s clinical superiority in metabolic management (Hankosky et al., 2025; Aronne et al., 2024; Liu et al., 2025; Garvey et al., 2025; Sattar et al., 2025; Ishimura et al., 2025).
Imaging-Based Evidence of Structural and Functional Improvements
One of the distinctive aspects of this review is the incorporation of imaging techniques to objectively assess tirzepatide’s effects. Magnetic resonance imaging (MRI) in the SURPASS-3 MRI trial demonstrated a reduction in intramuscular fat while preserving lean mass, highlighting a qualitative improvement in muscle composition (Sattar et al., 2025). Echocardiographic assessment in patients with heart failure with preserved ejection fraction (HFpEF) revealed improved diastolic function and favorable structural cardiac changes (Lin et al., 2025). Furthermore, Garvey et al. (2025) used imaging to quantify significant reductions in visceral and epicardial fat, findings that align with tirzepatide’s cardiometabolic benefits. These imaging-derived endpoints not only complement traditional biochemical markers but also provide tangible, visual evidence of the therapy’s systemic impact, reinforcing its role in a comprehensive treatment strategy for individuals with type 2 diabetes and obesity (Sattar et al., 2025; Lin et al., 2025; Garvey et al., 2025).
Additional Clinical Outcomes and Safety Considerations
Beyond weight and glycemic control, tirzepatide demonstrates positive effects on broader health outcomes. Gibble et al. (2025) found a significant improvement in self-reported quality of life among adults with obesity or overweight, suggesting that benefits extend to patient-perceived health status. Safety analyses conducted by Zeng et al. (2023) indicated a higher incidence of biliary events without an increased risk of pancreatitis, underlining the importance of ongoing monitoring. Di Stefano et al. (2025) addressed neuropsychiatric safety, finding no statistical association between tirzepatide and suicidal ideation or behavior. The therapy’s consistent efficacy across age groups, reported by Ishimura et al. (2025), also supports its versatility in clinical practice. These findings, when considered alongside cost-effectiveness data (Liu et al., 2025) and long-term adherence outcomes (Aronne et al., 2024), strengthen the rationale for its integration into standard care for metabolic disorders (Gibble et al., 2025; Zeng et al., 2023; Di Stefano et al., 2025; Ishimura et al., 2025; Liu et al., 2025; Aronne et al., 2024).
Conclusion
Tirzepatide demonstrates consistent superiority over semaglutide and insulin glargine in reducing HbA1c levels, promoting weight loss, and improving metabolic outcomes in individuals with type 2 diabetes and/or obesity. Beyond biochemical endpoints, evidence derived from imaging modalities such as magnetic resonance imaging and echocardiography reveals structural and functional benefits, including reduced intramuscular, visceral, and epicardial fat and improved cardiac diastolic function. These findings provide objective, visual confirmation of tirzepatide’s systemic effects and strengthen its role as a multifaceted therapeutic option.
Additional advantages include sustained weight maintenance, favorable cost-effectiveness, consistent efficacy across age groups, and improvements in patient-reported quality of life. Safety data indicate the need for monitoring biliary events, although no significant associations have been observed with pancreatitis or suicidal ideation. Taken together, these results position tirzepatide as a comprehensive treatment option capable of addressing multiple metabolic and cardiovascular targets, supported by robust clinical and imaging-based evidence.
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1Medical Doctor, graduated from Universidade de Ribeirão Preto, Campus Guarujá.
2PhD from Universidade Federal de São Paulo (UNIFESP), Medical Student at Universidade de Ribeirão Preto (UNAERP), Campus Guarujá.
3Medical Resident in Radiology at São Carlos Imagem (SCI).
4Medical Resident in Internal Medicine at Beneficência Portuguesa Hospital in Santos.
5Pediatrician. PhD student in Environmental Science and Technology at UNISANTA.
6Medical Doctor, graduated from Universidade do Oeste Paulista, Campus Guarujá.
7Nursing Student at Universidade de Ribeirão Preto (UNAERP), Campus Guarujá.
8Medical Student at Universidade de Ribeirão Preto (UNAERP), Campus Guarujá; Member of the Academic League of Legal Medicine and Medical Expertise of Guarujá (LAMELPM).
9Medical Student at Universidade de Ribeirão Preto (UNAERP), Campus Guarujá; Member of the Academic League of Legal Medicine and Medical Expertise of Guarujá (LAMELPM).
10Medical Student at Universidade de Ribeirão Preto (UNAERP), Campus Guarujá; Member of the Academic League of Legal Medicine and Medical Expertise of Guarujá (LAMELPM).
Corresponding author: Bianca Lunna Pereira da Silva Costa Barros, Email: dra.blodux@gmail.com