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International Journal of Pharmaceutical InvestigationNOW IN
Review

The Multifaceted Potential of Tirzepatide in Metabolic and Non-Metabolic Disorders

Thalal Mohamed1, Srimathi Mahadevan1, Jayashri Vidya Prabhakaran1, Sundari Venkatesan1, Mohammed Fayaz1, Vijayakumar Thangavel Mahalingam1★★ Corresponding author

  1. 1Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, INDIA.

CORRESPONDENCE

Vijayakumar Thangavel Mahalingam

Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, INDIA.

vijayakm2@srmist.edu.in

ORCID: 0000-0002-7749-3224

Received: 14-08-2025; Revised: 09-10-2025; Accepted: 24-12-2025.

Volume 16, Issue 2 · pp. 405–413 · PUBLISHED Apr-Jun 2026 · DOI: 10.5530/ijpi.20260349

View on IJPI original site ↗

ABSTRACT

Tirzepatide is redefining the treatment landscape for metabolic and non-metabolic disorders. By uniquely harnessing two critical hormonal pathways, the review provides comprehensive insights into how Tirzepatide’s dual mechanism of action sets it apart from existing therapies. Noteworthy findings from clinical and preclinical studies underscore Tirzepatide's potential in addressing complex conditions Highlighting its role in cardio protection, renal protection, neuroprotection, bone health in osteoporosis, reproductive health, respiratory health, genetic conditions management, cancer-associated weight gain, psychiatric illness and antipsychotic drug-induced obesity, inflammatory conditions, and other conditions. This comprehensive review not only underscores tirzepatide’s potential to address unmet clinical needs but also identifies key avenues for future research, aiming to elucidate its broader applicability and optimize patient outcomes. By highlighting these novel insights, this review positions tirzepatide as a transformative agent with the potential to redefine therapeutic paradigms across diverse medical domains.

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FULL TEXT

INTRODUCTION

Tirzepatide (TIR) is a novel dual Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) that represents a promising advancement in the treatment of metabolic diseases, particularly obesity and Type 2 Diabetes Mellitus (T2DM). Approved by the FDA in 2022 for the management of T2DM and obesity, TIR operates by acting on both the GLP-1 and GIP receptors, two critical hormonal systems involved in glucose metabolism, appetite regulation, and energy homeostasis. These two pathways have historically been targeted individually by separate classes of medications, but TIR’s unique Mechanism of Action (MOA) offers a synergistic approach that enhances its therapeutic effects (Syed, 2022). GLP-1RAs like liraglutide and semaglutide have demonstrated efficacy in improving glycemic control, promoting weight loss, and reducing cardiovascular risk factors. However, TIR’s dual-action, leveraging both the GLP-1 and GIP receptors, sets it apart by improving Insulin Sensitivity (IS) and increasing insulin secretion in response to meals, while also reducing appetite and increasing satiety through effects on the central nervous system. The GIP receptor activation is not present in other GLP-1 RAs, it is thought to improve lipid metabolism and further enhance the weight loss effects, potentially making TIR more effective in managing obesity compared to traditional GLP-1 RAs alone. One of the most notable advantages of TIR is its superior efficacy compared to other GLP-1RAs and metabolic drugs (Jensterle, Rizzo, Haluzík, and Janež, 2022). Clinical studies have shown that TIR leads to significantly greater weight loss than other GLP-1RAs like semaglutide, and it also provides superior blood glucose control in patients with T2DM (Mather et al., 2022). TIR’s potential extends beyond weight loss and glycemic control, as emerging evidence suggests it also provides protective benefits across several organ systems, making it an exciting candidate for broader therapeutic applications. In this review, we will explore how TIR can influence not only obesity and diabetes but also other important aspects like cardio protection, renal protection, neuroprotection, bone health in osteoporosis, reproductive health, respiratory health, genetic conditions management, cancer-associated weight gain, psychiatric illness and antipsychotic drug-induced obesity, inflammatory conditions, and other conditions. This comprehensive understanding could pave the way for its broader use in clinical practice, offering potential benefits for a wide array of patients suffering from diverse health conditions. Figure 1: Multifaceted effects of Tirzepatide as a GLP-1/GIP receptor agonist on metabolic and non-metabolic disorders, highlighting its systemic benefits across various organ systems.

Figure 1: This diagram shows the effects of Tirzepatide, a GLP-1/GIP receptor agonist, on various systems. It highlights benefits like weight loss, improved insulin sensitivity, reduced inflammation, and better heart and kidney health. It also impacts hormones, bone health, and gut function, while lowering the risk of obesity-related cancer.

Tirzepatide In Metabolic Health

TIR addresses several key mechanisms contributing to prediabetic conditions, including IR (IR), beta-cell dysfunction, impaired glucose transport, hepatic glucose overproduction, and impairments in the incretin system (involving hormones like GLP-1 and GIP). These dysfunctions lead to chronic hyperglycemia and increased insulin secretion, which, over time, progress to T2DM. (Hankosky et al., 2023) conducted a 72-week clinical study showing that TIR significantly reduces the risk of developing T2DM in individuals with obesity or overweight, regardless of glycemic status. It is also effective for patients with IR, dyslipidemia, and hypertension. Phase 3 trials by (Jastreboff et al., 2024) reported significant reductions in body weight and IR compared to placebo, indicating TIR’s potential in preventing T2DM progression. Additionally, TIR has been found safe for children aged 10 and older, presenting a promising pharmacological option for managing pediatric obesity and controlling both glycemia and weight in this vulnerable population (Guan, Li, and Ma, 2023). While TIR shows promise, clinical trials specifically targeting adolescents with T2DM are still needed to assess its safety and effectiveness in this group. However, the increasing number of trials registered in the U.S. Clinical Trials Registry indicates growing interest in its potential for younger populations. A Phase 2 study by (Mather et al., 2022) demonstrated that TIR significantly improves IS compared to semaglutide, with benefits extending beyond weight loss. (Jastreboff et al., 2022) also emphasized that TIR (15 mg) achieved comparable weight-loss outcomes to bariatric surgery, with 36.2% of participants achieving ≥25% body weight reduction, positioning it as a viable, non-surgical alternative for obesity management. This makes TIR a promising treatment option for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Phase 2 clinical trials by (Loomba et al., 2024) showed that TIR outperformed placebo in resolving Metabolic dysfunction-Associated Steatohepatitis (MASH) without exacerbating fibrosis, also improving fibrosis staging outcomes. TIR has also demonstrated significant reductions in hypertriglyceridemia, a key component of metabolic syndrome. In the SURPASS-2 trial, TIR led to greater reductions in serum triglyceride levels compared to semaglutide 1 mg (Nicholls et al., 2024). Furthermore, a meta-analysis by (Zeng et al., 2023) found that TIR was not significantly associated with an increased risk of pancreatitis or gallbladder-related diseases, supporting its general safety in these areas, although further research is needed to confirm these findings.

Tirzepatide in bone health

(Mabilleau G et al., 2014) conducted a meta-analysis on the effects of GLP-1RAs on osteoporosis, identifying 28 eligible studies. Among these, 21 studies reported no fractures, while 7 studies observed at least one fracture in patients receiving GLP-1RA treatment. The analysis suggested a potential protective effect of GLP-1RAs against fractures in placebo-controlled and high-quality studies, although these findings were not statistically significant. The results exhibited variability, with some trials indicating a trend toward reduced fracture risk, while others showed no effect or even an increased risk, particularly in lower-quality studies. Similarly, (Gabe et al., 2022). studied the combined effects of GIP and glucagon-like peptide-2 (GLP-2) RA, finding that their co-administration resulted in an additive reduction in bone resorption, which was more effective than either hormone alone. This indicates that combining GIP and GLP-2RA can synergistically improve bone metabolism, In comparison, TIR, a dual GLP-1/GIP RA, and known to reduce systemic inflammation measured by C-Reactive Protein (CRP) (Borlaug et al., 2024) could potentially reduce osteoporosis through multiple mechanisms, including reducing body weight, anti-inflammatory activity and suppressing osteoclast activity, ultimately improving bone health.

Tirzepatide in reproductive system health

The studies on GIP receptor agonists all investigated the effects of receptor agonists in overweight women with PCOS, focusing on both reproductive and metabolic outcomes. GLP-1RAs, particularly when combined with metformin, significantly improved menstrual cycle regularity, ovulation rates, and androgen levels, enhancing hormonal and reproductive health. These therapies were also more effective than metformin alone in promoting weight loss, particularly reducing abdominal fat, and improving IS and glucose metabolism (Elkind-H et al., 2008). (Nylander et al., 2017) observed reductions in body weight; improvements in markers of hyperandrogenism (e.g., increased Sex Hormone-Binding Globulin (SHBG) and decreased free testosterone, and a modest reduction in ovarian volume, indicating a positive effect on ovarian morphology. (Kahal et al., 2015) further emphasized that GLP-1 analogs contributed to reduced testosterone levels, offering benefits for hyperandrogenism, which is often linked to IR and obesity in PCOS. Additionally, the GIP receptor plays a critical role in improving IS by enhancing glucose-dependent insulin secretion and promoting fat metabolism. This reduction in IR lowers circulating insulin levels, which can decrease testosterone production, a common issue in women with PCOS. Elevated insulin stimulates the ovaries to produce more testosterone, exacerbating hyperandrogenism. By improving IS, GIP receptor agonists help mitigates this hormonal imbalance. These agonists also support weight loss and fat metabolism, further contributing to better overall metabolic and reproductive outcomes. However, gastrointestinal side effects, such as nausea and constipation, were more frequent in the intervention groups (Samms, Coghlan, and Sloop, 2020). In conclusion, combining GLP-1/GIP receptor agonists may provide a more effective treatment strategy than individual therapies, addressing both metabolic dysfunction and androgen excess in PCOS.

Tirzepatide in cardiovascular health

Tirzepatide has demonstrated significant cardiovascular and metabolic benefits across various high-risk populations, including individuals with type 2 diabetes, obesity-related Heart Failure with preserved Ejection Fraction (HFpEF), moderate-to-severe Obstructive Sleep Apnea (OSA), and dyslipidemia. In a 52-week study, (Borlaug et al., 2024) reported reductions in systolic blood pressure (-5 mmHg), estimated blood volume (-0.58 L), and systemic inflammation, evidenced by a 37.2% decrease in CRP levels. Additionally, a significant 10.4% reduction in troponin T levels suggested potential mitigation of cardiac injury. (Frías et al., 2021) and (Del Prato et al., 2021) further emphasized TIR’s lipid-modifying effects, showing improvements in triglycerides, Very-Low-Density Lipoprotein (VLDL), and High-Density Lipoprotein (HDL) cholesterol compared to semaglutide. Similarly, demonstrated dose-dependent reductions in lipid parameters, including serum triglycerides (up to 23%), LDL cholesterol (up to 8%), and non-HDL cholesterol (up to 12%) over a 52-week period compared to insulin glargine (Del Prato et al., 2021). The SURPASS trials reinforced these findings by showing consistent reductions in both systolic and diastolic blood pressure, with systolic reductions ranging from -4.7 mmHg to -6.6 mmHg across different trial phases (Forzano et al., 2022). In patients with OSA and obesity, (Malhotra et al., 2024) observed significant reductions in the Apnea-Hypopnea Index (AHI) by -25.3 events per hour in trial 1 and -29.3 events per hour in trial 2, along with improvements in body weight, hypoxic burden, high-sensitivity CRP, systolic blood pressure, and sleep quality. (Ludvik et al., 2021) added to the evidence, demonstrating that TIR provides superior glycaemic control compared to insulin degludec while significantly reducing the incidence of hypoglycaemic events. This dual benefit of enhanced glucose regulation and reduced hypoglycaemia may contribute to cardioprotection by minimizing cardiovascular stress. Overall, TIR demonstrated substantial benefits in reducing sleep apnea severity and improving cardiovascular markers, emphasizing its potential in managing cardiovascular risk and metabolic health in diverse patient populations.

Tirzepatide in renal health

TIR demonstrated significant cardiovascular and renal benefits. Kidney function was assessed using estimated Glomerular Filtration Rate (eGFR)-creatinine and eGFR-cystatin Cat baseline, with values similar for both TIR and insulin glargine. Over a 52-week period, TIR showed a smaller decline in kidney function, with less reduction in both eGFR-creatinine and eGFR-cystatin C compared to insulin glargine. No significant subgroup differences in eGFR changes were observed. Additionally, small but statistically significant correlations were found between changes in HbA1c and eGFR-cystatin C, suggesting a mild association between glycemic control and kidney function (Heerspink et al., 2023). Over 104 weeks, TIR continued to demonstrate kidney-protective effects, with a better long-term eGFR slope and sustained benefits even after discontinuation, despite an initial modest eGFR decline. TIR also reduced albuminuria progression, indicating decreased glomerular hypertension, with a greater proportion of participants achieving significant improvements, particularly in those with greater baseline kidney impairment. These renal benefits were dose-dependent and consistent across subgroups (Heerspink et al., 2022). In addition to its renal effects, TIR showed cardiovascular advantages, including reductions in systolic blood pressure, pulse pressure, and markers of inflammation like CRP, suggesting improved aortic compliance. Furthermore, TIR improved glycemic control, significantly reduced HbA1c levels, and led to substantial body weight reductions, which are attributed to its unique mechanism of dual GLP-1/GIP receptor agonism (Borlaug et al., 2024). (Urva S. et al., 2021) conducted a Pharmacokinetic (PK) study to assess TIR exposure in individuals with varying levels of renal impairment. The results showed that TIR exposure was similar across all groups, including those with renal dysfunction and healthy controls. While a slight increase in exposure was noted in the group with moderate renal impairment, it was not deemed clinically significant. Furthermore, no meaningful relationship was found between TIR exposure and kidney function, even in patients with severe renal impairment or end-stage renal disease. Overall, the study concluded that renal impairment does not have a significant impact on TIR pharmacokinetics. It can be effectively used to treat type 2 diabetes, obesity, and other related conditions, even in patients with renal impairment, as its PKs remain largely unaffected by varying degrees of kidney dysfunction. These multifaceted benefits make TIR a promising treatment for individuals with both metabolic and renal complications.

Tirzepatide in neurological health

Obesity is strongly associated with an increase in both the frequency and severity of migraines. Individuals who are severely obese are nearly twice as likely to experience severe headache pain compared to those with a normal weight. As obesity worsens, migraine frequency also rises, with 13.4% of obese individuals and 20.7% of severely obese individuals reporting frequent headaches (10-14 days per month). This increase in migraine frequency and severity is compounded by factors such as sympathetic dysregulation, reduced serotonin levels, and inflammation, which contribute to more frequent and intense headaches. Behavioral factors like low physical activity and conditions such as obstructive sleep apnea further exacerbate migraine outcomes. Given these challenges, interventions targeting obesity may offer benefits for individuals suffering from both obesity and migraines (Bond, Roth, Nash, and Wing, 2011). In this, TIR has shown promise. Both (Jastreboff AM et al., 2022) and (Heise T et al., 2023) examined the effects of TIR on body weight in individuals with obesity. (Jastreboff AM et al., 2022) conducted a 72-week study and found significant and sustained reductions in body weight with weekly doses of TIR (5 mg, 10 mg, or 15 mg). (Heise et al., 2023) showed that TIR led to greater reductions in body weight and fat mass compared to both placebo and semaglutide. In both studies, TIR was shown to significantly reduce appetite compared to placebo, with no significant differences in appetite scores or energy intake reductions between TIR and semaglutide. It reduces the pro-apoptotic BAX/Bcl-2 ratio, modulates apoptotic markers, and activates the CREB and BDNF signaling pathways to enhance neuronal survival and synaptic activity (Fontanella et al., 2024). (Yang et al., 2024) demonstrated that weekly TIR administration (10 nmol/kg for 8 weeks) in APP/PS1 Alzheimer's disease mice reduced cortical amyloid plaques, Aβ-induced neuronal apoptosis, and astrocytic activation (GFAP), despite a paradoxical decrease in GLP-1R protein expression. Furthermore, TIR improved glucose regulation, upregulated mRNAs linked to glucose metabolism in the hypothalamus (GLP-1R, SACF1, ATF4, Glu2A, Glu2B) and cortex (glucose transporter 1, hexokinase, glucose-6-phosphate dehydrogenase, phosphofructokinase), and mitigated Aβ-induced mitochondrial dysfunction by regulating ROS, stabilizing mitochondrial membrane potential, and ensuring ATP production. These findings suggest that TIR may help reduce both obesity and its associated complications, including migraines, potentially improving the quality of life for individuals affected by both conditions.

(Kalinderi, Papaliagkas, and Fidani, 2024) further highlight TIR's promising neuroprotective mechanisms, emphasizing its ability to reduce inflammation, oxidative stress, and apoptosis while promoting neurogenesis and improving mitochondrial function to prevent dopaminergic neuronal death. Preclinical evidence demonstrates that TIR and related incretin-based therapies protect neurons from toxins such as rotenone, MPTP, and 6-OHDA by enhancing autophagy and reducing neuroinflammation. GLP-1RAs like exendin-4, liraglutide, lixisenatide, and semaglutide have shown efficacy in protecting the nigrostriatal dopaminergic system and mitigating inflammatory and apoptotic pathways. Dual GLP-1/GIP receptor agonists, including DA5-CH and DA-JC1, exhibit superior neuroprotection by reducing α-synuclein aggregation and enhancing dopamine synthesis. Comparative studies reveal that certain dual agonists outperform single agonists like NLY01 and liraglutide in neuroprotection and inflammation suppression. Clinical evidence from trials with exendin-4, liraglutide, and lixisenatide underscores their potential, with improvements in motor and cognitive function and reductions in disability scores. Despite side effects such as nausea and weight loss, the sustained benefits post-treatment highlights their promise. TIR, given its dual-agonist nature and broader metabolic effects, holds great potential for a personalized treatment approach in Alzheimer and Parkinson’s disease management.

Tirzeaptide in respiratory health

Obesity, a condition known to impair pulmonary function and exacerbate airway inflammation, was a key focus in the study by (Toki et al., 2023) investigating TIR in polygenic obese TALLYHO Jng/J mice. The drug demonstrated significant metabolic and anti-inflammatory benefits, achieving greater bodyweight reduction, improved glycemic control, and decreased serum leptin levels compared to semaglutide and [D-Ala2]-GIP. It also reduced Th2 cytokines, including IL-5 and IL-33, and eosinophil and lymphocyte counts in Bronchoalveolar Lavage Fluid (BALF), highlighting its potential for alleviating allergic inflammation. However, its effects on certain markers like CCL17 and CCL22 were comparable to semaglutide, and it did not improve airway responsiveness or significantly impact neutrophil-related inflammation. The findings suggest that TIR offers specific advantages but has limitations in its broader anti-inflammatory efficacy combained with weight loss effect of TIR could help improve asthma control and reduce the burden of obstructive sleep apnea and other obesity-related pulmonary issues (Forzano et al., 2022).

Tirzepatide in genetic conditions

The study by (Ganawa, Santhosh, Parry, and Syed, 2022) discusses the use of GLP-1RAs for managing obesity in patients with Bardet-Biedl Syndrome (BBS). The patient in this case report initially received liraglutide, resulting in a significant weight reduction over five months. This was later replaced with semaglutide for convenience, resulting in further weight loss and improved metabolic control. The patient achieved a final BMI of 24.3 kg/m² after 19 months, demonstrating that GLP-1RAs can effectively manage obesity and associated metabolic complications in BBS. TIR may help alleviate some symptoms of Alström syndrome, a rare genetic disorder characterized by obesity, type 2 diabetes, vision and hearing loss, and cardiovascular issues (Ryan, 2021). Its dual mechanism, activating both GLP-1 and GIP receptors, improves IS (Mather et al., 2022), lowers blood sugar, and reduces inflammation, potentially benefiting individuals with IR and metabolic disturbances. TIR also promotes weight loss by reducing appetite and fat accumulation, helping manage obesity (Borlaug et al., 2024). Additionally, it can improve lipid profiles and support heart health, addressing cardiovascular complications (Del Prato et al., 2021). However, it does not treat vision or hearing loss. Even in Wolfram Syndrome, TIR does not address the underlying WFS1 or CISD2 mutations, which lead to Endoplasmic Reticulum (ER) stress, beta-cell apoptosis, and neurodegeneration. However, as a dual GIP and GLP-1RA, it enhances insulin secretion when beta-cell function is intact, suppresses glucagon release, slows gastric emptying, and reduces postprandial glucose levels. Additionally, GLP-1RAs are known to reduce inflammation, potentially alleviating ER stress, and promote weight loss, while GIP improves IS and supports metabolic regulation. Both pathways exhibit cytoprotective and neuroprotective activities (Boshchenko et al., 2024). Despite these benefits, in Wolfram Syndrome, the beta-cell loss is often severe and irreversible, and TIR does not directly modulate the genetic mutation or fully counteract the progression of neurodegeneration. Nevertheless, a Phase 2 clinical trial (NCT05659368) registered in the U.S. shows promise in exploring TIR's role in managing Wolfram Syndrome, offering hope for improved outcomes or at least better symptom control (Clinicaltrials.gov). In the treatment of hidradenitis suppurativa, (Chan, Kaur, and Kaffenberger, 2024) demonstrated the potential in improving HS with metabolic comorbidities. Administered at 2.5 mg weekly and titrated to 7.5 mg, TIR significantly reduced HS severity (improved DLQI, VAS, and HS-PGA) while decreasing inflammatory lesions. It also achieved substantial metabolic benefits, including HbA1c reduction in half, triglyceride improvement, and 16% weight loss. These outcomes suggest TIR's synergistic impact on HS and metabolic control. TIR also shows promise as a treatment for rare lipodystrophy syndromes, where the loss of subcutaneous fat results in ectopic fat deposition in the liver, muscles, and visceral regions. These abnormal fat accumulations exacerbate IR, hepatic steatosis, and systemic inflammation, contributing to metabolic dysfunction (Zammouri et al., 2022). TIR promotes fat mobilization from ectopic sites, reduces hepatic fat accumulation, improves dyslipidemia, and modulates inflammatory pathways, potentially mitigating organ-specific damage.

Tirzepatide in cancer associated weight loss

Cancers are significantly influenced by obesity, which is a major risk factor for endometrial cancer and atypical hyperplasia; these patients often undergo progestin therapy, but high recurrence rates persist as the underlying cause-obesity-remains unaddressed (Onstad, Schmandt, and Lu, 2016). TIR holds promise as a weight loss agent to improve reproductive and oncological outcomes. In node-positive high-risk early breast cancer patients with obesity or overweight, adding TIR as an adjuvant therapy could enhance outcomes compared to standard therapies alone. The anti-inflammatory properties of GLP-1RAs, including their ability to reduce CRP, TNF-α, IL-6 (Batiha et al., 2023) and Myeloid-Derived Suppressor Cells (MDSCs), contribute to mitigating systemic inflammation, IR, and hyperglycemia-all factors associated with increased MDSC levels and tumor-promoting inflammation (Wang et al., 2021). Obesity-related chronic low-grade inflammation, driven by adipokines and macrophage infiltration, further exacerbates MDSC activity, indirectly addressed by TIR’s mechanisms. Drugs like ruxolitinib, used to treat polycythemia vera, often cause weight gain (Krichevsky et al., 2018), and GLP-1RAs like TIR could counteract this while preventing hyperglycemia. Moreover, TIR may support long-term weight and metabolic health (Jastreboff et al., 2024) in cancer survivors at risk of recurrence or secondary cancers due to obesity. Notably, a retrospective study by (L. Wang, et al. 2024) demonstrated a significant reduction in pancreatic cancer risk among GLP-1RA users, particularly in obese individuals or those with tobacco use disorder, with even greater risk reduction observed in combination therapies. Furthermore, hormonal therapy in breast and prostate cancer frequently causes weight gain (Pati, et al., 2023), which TIR could address through improved metabolic control and appetite regulation, potentially delivering substantial benefits in weight management and overall cancer care (Heise et al., 2023) even Supporting long-term weight and metabolic health in cancer survivors at risk for recurrence or secondary cancers due to obesity.

Trizepatide in psychatric illness

Patients with Binge Eating Disorder (BED) are often obese and require both psychological and pharmacological treatments to manage their symptoms. While many drugs, including antidepressants and antipsychotics, are commonly prescribed, the obesity associated with BED often remains unaddressed. A systematic review by (Aoun et al., 2024) highlighted favorable results in weight management when GLP-1RAs were used alongside standard therapies. TIR, a GLP-1RA, has the potential to manage obesity effectively. This is particularly important given the weight gain commonly caused by chronic use of antipsychotic medications such as olanzapine and clozapine (Dayabandara et al., 2017). TIR’s ability to suppress appetite and reduce cravings makes it a promising option for achieving weight reduction in such cases (Heise et al., 2023).

Tirzepatide in inflammatory conditions

Obesity is strongly linked to several autoimmune diseases. By promoting significant weight loss, TIR helps reduce chronic low-grade inflammation and immune dysregulation, key drivers of autoimmune disease progression and severity. Weight reduction achieved through TIR can alleviate disease activity in conditions like rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, while also improving therapeutic responses in Hashimoto’s thyroiditis, autoimmune hepatitis, and inflammatory bowel disease. Adolescence-associated obesity that Increase the risk of conditions like multiple sclerosis, TIR’s ability to regulate appetite, reduce cravings, and enhance metabolic health can mitigate the impact of obesity, ultimately improving outcomes and reducing the burden of autoimmune diseases particularly it reduces levels of cytokines such as TNF-α, IL-1β, and IL-6 (Chen et al., 2024) which are elevated in Inflammatory Bowel Disease (IBD) and drive intestinal inflammation and enhancing the integrity of the intestinal epithelial barrier, GLP-1 prevents translocation of bacterial endotoxins (Y. Zeng et al., 2024) and also slows gastric emptying and intestinal motility reduces further mechanical stress on inflamed bowel segments and epithelial cell proliferation could repair IBD lesions (Karrar et al., 2023). Additionally, obesity is a known aggravating factor in IBD severity due to its contribution to systemic and gut inflammation. TIR’s synergistic effect in enhancing metabolic benefits and lower systematic inflammation contributing to IBD. (Arvanitakis et al., 2023). Reviewed numerous animal studies highlighting the anti-inflammatory potential of GLP-1 RA in the context of IBD, with a particular focus on the cAMP/NF-κB pathway. These studies demonstrated significant reductions in pro-inflammatory cytokines such as TNF-α and IL-1α and a notable downregulation of NF-κB phosphorylation, a key regulator of intestinal immune function. Additionally, GLP-1 RA was shown to improve colitis symptoms in animal models (W. Wang et al., 2023), including enhanced stool consistency, decreased histological inflammation, and attenuation of associated diarrhea. Furthermore, improvements in gut microbiota regulation (Silva-Veiga et al., 2025) and the restoration of GLP-1 production from short-chain fatty acids were observed, suggesting a multifaceted therapeutic potential for GLP-1 RA in managing IBD.

Tirzepaide in other conditions

Post-transplant patients often struggle with obesity due to steroids and metabolic changes due to the glucocorticoticoids alter the activity of AMP-activated protein kinase in the hypothalamus and decrease Uncoupling Protein 1 (UCP-1) and activates endocannabinoid system (Hu et al., 2019; Bowles et al., 2015) all these combine leads to reduced metabolic rates, increase in food intake and decrease in energy expenditure GLP-1/GIP Receptor agonist can be used to decrease the appetite and suppress the food craving and enhance IS (Heise et al., 2023). Even in patient with and Antiretroviral Therapy (ART) often experience metabolic changes and IR is most common in older protease inhibitors and NRTIs contribute to poor glycemic control and dyslipidemia often lead to obesity, inflammation and metabolic dysfunction (Ergin, Inga, Maung, Javed, and Khan, 2020) TIR can be used to treat these metabolic dysregulations with ART.

Future Directions

This review underscores the potential of TIR in addressing a broad spectrum of metabolic and non-metabolic disorders. While current research demonstrates promising short-term efficacy, there remains an urgent need for longitudinal studies to evaluate the safety profile and long-term adverse effects of TIR across diverse patient populations. Understanding the precise mechanisms by which TIR exerts its effects on various organ systems is critical for optimizing its therapeutic application and dosing regimens. The role of TIR in adolescent populations is notably underexplored, necessitating further investigation to assess its safety, efficacy, and outcomes in this demographic. This review highlights the potential of TIR as an adjuvant therapy in combination with other therapeutic agents, which could enhance its clinical efficacy. Rigorous clinical trials are warranted to elucidate the synergistic benefits of such combinatorial approaches. Emerging evidence also suggests that TIR may possess neuroprotective and anti-inflammatory properties, opening new avenues for its application in neurological disorders. Comprehensive studies are required to explore its therapeutic role in these conditions. Additionally, the use of TIR in cancer-related weight management and as an adjunct therapy to improve treatment outcomes in oncology represents an area of significant clinical interest. Genetic and phenotypic variations among patients may influence their responses to TIR. Future research should prioritize identifying predictive biomarkers to facilitate the development of personalized treatment strategies. Furthermore, robust studies assessing the impact of TIR on patients’ quality of life, including psychological and functional well-being, are needed. Real-world evidence, obtained through observational studies, could provide critical insights into the effectiveness and safety of TIR in routine clinical practice. As its therapeutic potential expands, careful consideration of the regulatory, economic, and policy implications of its broader use will be essential. In summary, while TIR shows immense promise in managing a range of disorders, ongoing research must focus on addressing knowledge gaps related to its mechanisms, safety, long-term outcomes, and broader clinical applications.

CONCLUSION

TIR represents a significant advancement in the treatment of obesity, T2DM, and a range of other metabolic and non-metabolic disorders. The evidence gathered from clinical studies demonstrates TIR's superior efficacy in improving glycemic control, promoting weight loss, and offering protective benefits across various organ systems. TIR's unique mechanism of action provides synergistic effects that enhance insulin sensitivity, reduce appetite, and improve lipid metabolism. This multifaceted approach not only addresses the primary symptoms of obesity and T2DM but also offers promising therapeutic potential in areas such as cardiovascular health, renal function, neurological protection, and bone health. The comprehensive analysis of TIR's applications extends beyond metabolic diseases, highlighting its potential in managing reproductive health disorders like PCOS, mitigating cardiovascular risks, supporting renal health, and offering neuroprotection in conditions such as Alzheimer's and Parkinson's disease. Moreover, TIR shows promise in addressing weight-related complications in cancer, psychiatric illnesses, and various inflammatory and genetic conditions. Despite the promising results, further research is essential to fully understand the long-term efficacy and safety of TIR. Future studies should focus on elucidating the underlying mechanisms, exploring its use in pediatric populations, and investigating combination therapies. Additionally, the potential of TIR in personalized medicine and its cost-effectiveness should be evaluated to maximize its clinical utility. Tirzepatide offers a groundbreaking approach to managing a broad spectrum of health conditions, providing hope for improved therapeutic outcomes and enhancing the quality of life for patients with diverse health challenges.

REFERENCES

As published

Showing references and in-text citations exactly as published.

  1. 1.Aoun, L.; Almardini, S.; Saliba, F.; Haddadin, F.; Mourad, O.; Jdaidani, J. et al. GLP-1 receptor agonists: A novel pharmacotherapy for binge eating (binge eating disorder and bulimia nervosa)? A systematic review. Journal of Clinical and Translational Endocrinology. 2024;35:Article 100333. https://doi.org/10.1016/j.jcte.2024.100333DOIGOOGLE SCHOLAR
  2. 2.Arvanitakis, K.; Koufakis, T.; Popovic, D.; Maltese, G.; Mustafa, O.; Doumas, M. et al. GLP-1 receptor agonists in obese patients with inflammatory bowel disease: From molecular mechanisms to clinical considerations and practical recommendations for safe and effective use. Current Obesity Reports. 2023;12(2):61–74. https://doi.org/10.1007/s13679-023-00506-3DOIGOOGLE SCHOLAR
  3. 3.Batiha, G. E.-S.; Al-kuraishy, H. M.; Al-Gareeb, A. I.; Ashour, N. A.; Negm, W. A.. Potential role of tirzepatide towards Covid-19 infection in diabetic patients: a perspective approach. Inflammopharmacology. 2023;31(4):1683–1693. https://doi.org/10.1007/s10787-023-01239-4DOIGOOGLE SCHOLAR
  4. 4.Bond, D. S.; Roth, J.; Nash, J. M.; Wing, R. R.. Migraine and obesity: Epidemiology, possible mechanisms and the potential role of weight loss treatment. Obesity Reviews: An Official Journal of the International Association for the Study of Obesity. 2011;12(5):e362–e371. https://doi.org/10.1111/j.1467-789X.2010.00791.xDOIGOOGLE SCHOLAR
  5. 5.Borlaug, B. A.; Zile, M. R.; Kramer, C. M.; Baum, S. J.; Hurt, K.; Litwin, S. E. et al. Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: A secondary analysis of the SUMMIT trial. Nature Medicine. 2025;31(2):544–551. https://doi.org/10.1038/s41591-024-03374-zDOIGOOGLE SCHOLAR
  6. 6.Boshchenko, A. A.; Maslov, L. N.; Mukhomedzyanov, A. V.; Zhuravleva, O. A.; Slidnevskaya, A. S.; Naryzhnaya, N. V. et al. Peptides are cardioprotective drugs of the future: The receptor and signaling mechanisms of the cardioprotective effect of glucagon-like peptide-1 receptor agonists. International Journal of Molecular Sciences. 2024;25(9):4900. https://doi.org/10.3390/ijms25094900DOIGOOGLE SCHOLAR
  7. 7.Bowles, N. P.; Karatsoreos, I. N.; Li, X.; Vemuri, V. K.; Wood, J.-A.; Li, Z. et al. Proceedings of the National Academy of Sciences of the United States of America. 2015;112(1):285–290. https://doi.org/10.1073/pnas.1421420112DOIGOOGLE SCHOLAR
  8. 8.Chan, L. J.; Kaur, M.; Kaffenberger, B. H.. A case of recalcitrant hidradenitis suppurativa concomitantly treated with tirzepatide. JAAD Case Reports. 2024;52:101–102. https://doi.org/10.1016/j.jdcr.2024.02.023DOIGOOGLE SCHOLAR
  9. 9.Chen, L.; Chen, X.; Ruan, B.; Yang, H.; Yu, Y.. Tirzepatide protects against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and inflammation via PI3K/Akt signaling. Peptides. 2024;178:Article 171245. https://doi.org/10.1016/j.peptides.2024.171245DOIGOOGLE SCHOLAR
  10. 10.Clinicaltrials.Gov.. n.d..GOOGLE SCHOLAR
  11. 11.Dayabandara, M.; Hanwella, R.; Ratnatunga, S.; Seneviratne, S.; Suraweera, C.; de Silva, V. A.. Antipsychotic-associated weight gain: Management strategies and impact on treatment adherence. Neuropsychiatric Disease and Treatment. 2017;13:2231–2241. https://doi.org/10.2147/NDT.S113099DOIGOOGLE SCHOLAR
  12. 12.Del Prato, S.; Kahn, S. E.; Pavo, I.; Weerakkody, G. J.; Yang, Z.; Doupis, J. et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): A randomised, open-label, parallel-group, multicentre, phase 3 trial. The Lancet. 2021;398(10313):1811–1824. https://doi.org/10.1016/S0140-6736(21DOIGOOGLE SCHOLAR
  13. 13.Elkind-Hirsch, K.; Marrioneaux, O.; Bhushan, M.; Vernor, D.; Bhushan, R.. Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. The Journal of Clinical Endocrinology and Metabolism. 2008;93(7):2670–2678. https://doi.org/10.1210/jc.2008-0115DOIGOOGLE SCHOLAR
  14. 14.Ergin, H. E.; Inga, E. E.; Maung, T. Z.; Javed, M.; Khan, S.. HIV, antiretroviral therapy and metabolic alterations: A review. Cureus. 2020;12(5):Article e8059. https://doi.org/10.7759/cureus.8059DOIGOOGLE SCHOLAR
  15. 15.Fontanella, R. A.; Ghosh, P.; Pesapane, A.; Taktaz, F.; Puocci, A.; Franzese, M. et al. Tirzepatide prevents neurodegeneration through multiple molecular pathways. Journal of Translational Medicine. 2024;22(1):114. https://doi.org/10.1186/s12967-024-04927-zDOIGOOGLE SCHOLAR
  16. 16.Forzano, I.; Varzideh, F.; Avvisato, R.; Jankauskas, S. S.; Mone, P.; Santulli, G.. Tirzepatide: A systematic update. International Journal of Molecular Sciences. 2022;23(23):Article 14631. https://doi.org/10.3390/ijms232314631DOIGOOGLE SCHOLAR
  17. 17.Frías, J. P.; Davies, M. J.; Rosenstock, J.; Pérez Manghi, F. C.; Fernández Landó, L.; Bergman, B. K. et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. The New England Journal of Medicine. 2021;385(6):503–515. https://doi.org/10.1056/NEJMoa2107519DOIGOOGLE SCHOLAR
  18. 18.Gabe, M. B. N.; Skov-Jeppesen, K.; Gasbjerg, L. S.; Schiellerup, S. P.; Martinussen, C.; Gadgaard, S. et al. GIP and GLP-2 together improve bone turnover in humans supporting GIPR-GLP-2R co-agonists as future osteoporosis treatment. Pharmacological Research. 2022;176:Article 106058. https://doi.org/10.1016/j.phrs.2022.106058DOIGOOGLE SCHOLAR
  19. 19.Ganawa, S.; Santhosh, S. H.; Parry, L.; Syed, A. A.. Weight loss with glucagon-like peptide-1 receptor agonists in Bardet‐Biedl syndrome. Clinical Obesity. 2022;12(5):Article e12546. https://doi.org/10.1111/cob.12546DOIGOOGLE SCHOLAR
  20. 20.Guan, R.; Li, X.; Ma, G.. Prediction of pediatric dose of tirzepatide from the reference adult dose using physiologically based pharmacokinetic modelling. Frontiers in Pharmacology. 2023;14:Article 1326373. https://doi.org/10.3389/fphar.2023.1326373DOIGOOGLE SCHOLAR
  21. 21.Hankosky, E. R.; Wang, H.; Neff, L. M.; Kan, H.; Wang, F.; Ahmad, N. N. et al. Tirzepatide reduces the predicted risk of developing type 2 diabetes in people with obesity or overweight: Post hoc analysis of the SURMOUNT‐1 trial. Diabetes, Obesity and Metabolism. 2023;25(12):3748–3756. https://doi.org/10.1111/dom.15269DOIGOOGLE SCHOLAR
  22. 22.Heerspink, H. J. L.; Sattar, N.; Pavo, I.; Haupt, A.; Duffin, K. L.; Yang, Z. et al. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: Post-hoc analysis of an open-label, randomised, phase 3 trial. The Lancet. Diabetes and Endocrinology. 2022;10(11):774–785. https://doi.org/10.1016/S2213-8587(22DOIGOOGLE SCHOLAR
  23. 23.Heerspink, H. J. L.; Sattar, N.; Pavo, I.; Haupt, A.; Duffin, K. L.; Yang, Z. et al. Effects of tirzepatide versus insulin glargine on cystatin C-based kidney function: A SURPASS-4 post hoc analysis. Diabetes Care. 2023;46(8):1501–1506. https://doi.org/10.2337/dc23-0261DOIGOOGLE SCHOLAR
  24. 24.Heise, T.; DeVries, J. H.; Urva, S.; Li, J.; Pratt, E. J.; Thomas, M. K. et al. Tirzepatide reduces appetite, energy intake, and fat mass in people with type 2 diabetes. Diabetes Care. 2023;46(5):998–1004. https://doi.org/10.2337/dc22-1710DOIGOOGLE SCHOLAR
  25. 25.Hu, X.; Wang, Y.; Sheikhahmadi, A.; Li, X.; Buyse, J.; Lin, H. et al. Effects of glucocorticoids on lipid metabolism and AMPK in broiler chickens’ liver. Comparative Biochemistry and Physiology. Part B, Biochemistry and Molecular Biology. 2019;232:23–30. https://doi.org/10.1016/j.cbpb.2019.02.001DOIGOOGLE SCHOLAR
  26. 26.Jastreboff, A. M.; Aronne, L. J.; Ahmad, N. N.; Wharton, S.; Connery, L.; Alves, B. et al. Tirzepatide once weekly for the treatment of obesity. The New England Journal of Medicine. 2022;387(3):205–216. https://doi.org/10.1056/NEJMoa2206038DOIGOOGLE SCHOLAR
  27. 27.Jastreboff, A. M.; Le Roux, C. W.; Stefanski, A.; Aronne, L. J.; Halpern, B.; Wharton, S. et al. Tirzepatide for obesity treatment and diabetes prevention. The New England Journal of Medicine. 2024. https://doi.org/10.1056/nejmoa2410819DOIGOOGLE SCHOLAR
  28. 28.Jensterle, M.; Rizzo, M.; Haluzík, M.; Janež, A.. Efficacy of GLP-1 RA approved for weight management in patients with or without diabetes: A narrative review. Advances in Therapy. 2022;39(6):2452–2467. https://doi.org/10.1007/s12325-022-02153-xDOIGOOGLE SCHOLAR
  29. 29.Kahal, H.; Aburima, A.; Ungvari, T.; Rigby, A. S.; Coady, A. M.; Vince, R. V. et al. The effects of treatment with liraglutide on atherothrombotic risk in obese young women with polycystic ovary syndrome and controls. BMC Endocrine Disorders. 2015;15(1):14. https://doi.org/10.1186/s12902-015-0005-6DOIGOOGLE SCHOLAR
  30. 30.Kalinderi, K.; Papaliagkas, V.; Fidani, L.. GLP-1 receptor agonists: A new treatment in Parkinson’s disease. International Journal of Molecular Sciences. 2024;25(7):3812. https://doi.org/10.3390/ijms25073812DOIGOOGLE SCHOLAR
  31. 31.Karrar, H. R.; Nouh, M. I.; Nouh, Y. I.; Nouh, M. I.; Khan Alhindi, A. S.; Hemeq, Y. H. et al. Tirzepatide-induced gastrointestinal manifestations: A systematic review and meta-analysis. Cureus. 2023;15(9):Article e46091. https://doi.org/10.7759/cureus.46091DOIGOOGLE SCHOLAR
  32. 32.Krichevsky, S.; Kermani, P.; Molle, N.; Silver, R. T.; Schafer, A. I.; Ritchie, E. K. et al. Ruxolitinib can lead to weight gain in patients with myeloproliferative neoplasms by uncoupling feeding from central Leptin signaling via JAK2/STAT3. Blood. 2018;132(Suppl. 1):4284–4284. https://doi.org/10.1182/blood-2018-99-119542DOIGOOGLE SCHOLAR
  33. 33.Loomba, R.; Hartman, M. L.; Lawitz, E. J.; Vuppalanchi, R.; Boursier, J.; Bugianesi, E. et al. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. The New England Journal of Medicine. 2024;391(4):299–310. https://doi.org/10.1056/NEJMoa2401943DOIGOOGLE SCHOLAR
  34. 34.Ludvik, B.; Giorgino, F.; Jódar, E.; Frias, J. P.; Fernández Landó, L.; Brown, K. et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): A randomised, open-label, parallel-group, phase 3 trial. The Lancet. 2021;398(10300):583–598. https://doi.org/10.1016/S0140-6736(21DOIGOOGLE SCHOLAR
  35. 35.Mabilleau, G.; Mieczkowska, A.; Chappard, D.. Use of glucagon-like peptide-1 receptor agonists and bone fractures: A meta-analysis of randomized clinical trials. Journal of Diabetes. 2014;6(3):260–266. https://doi.org/10.1111/1753-0407.12102DOIGOOGLE SCHOLAR
  36. 36.Malhotra, A.; Grunstein, R. R.; Fietze, I.; Weaver, T. E.; Redline, S.; Azarbarzin, A. et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity. The New England Journal of Medicine. 2024;391(13):1193–1205. https://doi.org/10.1056/NEJMoa2404881DOIGOOGLE SCHOLAR
  37. 37.Mather, K. J.; Mari, A.; Li, J.; Heise, T.; de Vries, J. H.; Urva, S. et al. 714-P: Greater improvement in insulin sensitivity per unit weight loss with tirzepatide compared with selective GLP-1 receptor agonism. Diabetes. 2022;71(Suppl. 1). https://doi.org/10.2337/db22-714-pDOIGOOGLE SCHOLAR
  38. 38.Nicholls, S. J.; Tofé, S.; Le Roux, C. W.; D’Alessio, D. A.; Wiese, R. J.; Pavo, I. et al. Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: A post hoc analysis from the SurPASS Clinical Trial Program. Cardiovascular Diabetology. 2024;23(1):63. https://doi.org/10.1186/s12933-024-02147-9DOIGOOGLE SCHOLAR
  39. 39.Nylander, M.; Frøssing, S.; Clausen, H. V.; Kistorp, C.; Faber, J.; Skouby, S. O.. Effects of liraglutide on ovarian dysfunction in polycystic ovary syndrome: A randomized clinical trial. Reproductive Biomedicine Online. 2017;35(1):121–127. https://doi.org/10.1016/j.rbmo.2017.03.023DOIGOOGLE SCHOLAR
  40. 40.Onstad, M. A.; Schmandt, R. E.; Lu, K. H.. Addressing the role of obesity in endometrial cancer risk, prevention, and treatment. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 2016;34(35):4225–4230. https://doi.org/10.1200/JCO.2016.69.4638DOIGOOGLE SCHOLAR
  41. 41.Pati, S.; Irfan, W.; Jameel, A.; Ahmed, S.; Shahid, R. K.. Obesity and cancer: A current overview of epidemiology, pathogenesis, outcomes, and management. Cancers. 2023;15(2):485. https://doi.org/10.3390/cancers15020485DOIGOOGLE SCHOLAR
  42. 42.Ryan, D. H.. Next generation antiobesity medications: Setmelanotide, semaglutide, tirzepatide and bimagrumab: What do they mean for clinical practice?. Journal of Obesity and Metabolic Syndrome. 2021;30(3):196–208. https://doi.org/10.7570/jomes21033DOIGOOGLE SCHOLAR
  43. 43.Samms, R. J.; Coghlan, M. P.; Sloop, K. W.. How may GIP enhance the therapeutic efficacy of GLP-1? Trends in Endocrinology and Metabolism:. TEM. 2020;31(6):410–421. https://doi.org/10.1016/j.tem.2020.02.006DOIGOOGLE SCHOLAR
  44. 44.Silva-Veiga, F. M.; Marinho, T. S.; de Souza-Mello, V.; Aguila, M. B.; Mandarim-de-Lacerda, C. A.. Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), positively impacts the altered microbiota of obese, diabetic, ovariectomized mice. Life Sciences. 2025;361:Article 123310. https://doi.org/10.1016/j.lfs.2024.123310DOIGOOGLE SCHOLAR
  45. 45.Syed, Y. Y.. Tirzepatide: First approval. Drugs. 2022;82(11):1213–1220. https://doi.org/10.1007/s40265-022-01746-8DOIGOOGLE SCHOLAR
  46. 46.Toki, S.; Zhang, J.; Printz, R. L.; Newcomb, D. C.; Cahill, K. N.; Niswender, K. D. et al. Dual GIPR and GLP‐1R agonist tirzepatide inhibits aeroallergen-induced allergic airway inflammation in mouse model of obese asthma. Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology. 2023;53(2):216–221. https://doi.org/10.1111/cea.14252DOIGOOGLE SCHOLAR
  47. 47.Urva, S.; Quinlan, T.; Landry, J.; Martin, J.; Loghin, C.. Effects of renal impairment on the pharmacokinetics of the dual GIP and GLP-1 receptor agonist tirzepatide. Clinical Pharmacokinetics. 2021;60(8):1049–1059. https://doi.org/10.1007/s40262-021-01012-2DOIGOOGLE SCHOLAR
  48. 48.Wang, L.; Wang, Q.; Li, L.; Kaelber, D. C.; Xu, R.. Glucagon-like peptide-1 receptor agonists and pancreatic cancer risk: Target trial emulation using real-world data. Journal of the National Cancer Institute. 2025;117(3):476–485. https://doi.org/10.1093/jnci/djae260DOIGOOGLE SCHOLAR
  49. 49.Wang, S.; Tan, Q.; Hou, Y.; Dou, H.. Emerging roles of myeloid-derived suppressor cells in diabetes. Frontiers in Pharmacology. 2021;12:Article 798320. https://doi.org/10.3389/fphar.2021.798320DOIGOOGLE SCHOLAR
  50. 50.Wang, W.; Zhang, C.; Zhang, H.; Li, L.; Fan, T.; Jin, Z.. The alleviating effect and mechanism of GLP-1 on ulcerative colitis. Aging. 2023;15(16):8044–8060. https://doi.org/10.18632/aging.204953DOIGOOGLE SCHOLAR
  51. 51.Yang, S.; Zhao, X.; Zhang, Y.; Tang, Q.; Li, Y.; Du, Y. et al. Tirzepatide shows neuroprotective effects via regulating brain glucose metabolism in APP/PS1 mice. Peptides. 2024;179:Article 171271. https://doi.org/10.1016/j.peptides.2024.171271DOIGOOGLE SCHOLAR
  52. 52.Zammouri, J.; Vatier, C.; Capel, E.; Auclair, M.; Storey-London, C.; Bismuth, E. et al. Molecular and cellular bases of lipodystrophy syndromes. Frontiers in Endocrinology. 2021;12:Article 803189. https://doi.org/10.3389/fendo.2021.803189DOIGOOGLE SCHOLAR
  53. 53.Zeng, Q.; Xu, J.; Mu, X.; Shi, Y.; Fan, H.; Li, S.. Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: A systematic review and meta-analysis. Frontiers in Endocrinology. 2023;14:Article 1214334. https://doi.org/10.3389/fendo.2023.1214334DOIGOOGLE SCHOLAR
  54. 54.Zeng, Y.; Wu, Y.; Zhang, Q.; Xiao, X.. Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases. mBio. 2024;15(1):Article e0203223. https://doi.org/10.1128/mbio.02032-23DOIGOOGLE SCHOLAR

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Mohamed, T., Mahadevan, S., Prabhakaran, J. V., Venkatesan, S., Fayaz, M., & Mahalingam, V. T. (2026). The Multifaceted Potential of Tirzepatide in Metabolic and Non-Metabolic Disorders. International Journal of Pharmaceutical Investigation, 16(2), 405–413. https://doi.org/10.5530/ijpi.20260349