Tirzepatide

Abstract

Over the past 2 decades, treatment for type 2 diabetes (T2D) has evolved with the introduction of medications that offer greater simplicity. The Simplicity of Diabetes Treatment Questionnaire (Sim-Q™) was developed to assess the simplicity or complexity of treatment for T2D. This study assessed the psychometric properties of the Sim-Q.

Abstract

Use of glucagon-like peptide-1 receptor agonists (GLP1-RA) for weight loss is increasing; implications in breast cancer (BC) survivors remain unclear.This retrospective cohort study evaluated treatment patterns, weight loss, and outcomes in BC survivors at an academic institution receiving GLP1-RA. We evaluated patients with non-metastatic (ductal carcinoma in situ (DCIS), stage 1-3) BC who received GLP1-RA (2005 - 2024). Linear regression models estimated associations between weight change and clinical factors. After excluding DCIS, propensity score matching (1:2) was used to match patients who received GLP1-RA with patients who did not, based on confounding covariates. Kaplan-Meier estimates and log-rank tests compared disease-free survival (DFS) and overall survival (OS) between GLP1-RA users versus non-users in the subgroup with invasive disease. We identified 1,022 patients; 79% had DM2. Median weight and body mass index at GLP1-RA initiation were 86.8 kg (47.2-175.0 kg) and 33.5 kg/m2 (18.9-61.8 kg/m2). In semaglutide or tirzepatide users (442, 43.2%), median weight change at 3, 6, and 12 months after GLP1-RA initiation was -1.9% (-13.2%-14.9%), -3.1% (-20.2%-19.0%), and -2.6% (-27.8%-11.5%), respectively. Endocrine therapy and metformin use were associated with weight gain and loss, respectively; invasive disease stage was linked to greater weight loss. GLP1-RA was not associated with DFS, but OS significantly differed between GLP1-RA users (n=810) and non-users (n=1620) (HR 0.37, 95% CI: 0.27-0.53, p<0.0001). In conclusion, in this real-world study in BC survivors, GLP1-RA was associated with modest weight loss and improved all-cause survival. Clinical trials are warranted to study GLP1-RA in this population.

Abstract

Pharmacological therapies are recommended for individuals with obesity. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1), and tirzepatide, a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist (GIP/GLP-1), are among the leading pharmacological options for obesity treatment. This network meta-analysis (NMA) aims to evaluate the comparative efficacy of these two agents in reducing body weight and improving glycemic parameters.

Abstract

Peptide-based therapeutics represent a rapidly expanding class of drugs. Endogenous peptides typically exhibit short elimination half-lives due to proteolytic cleavage and renal filtration. However, modifications such as amino acid substitutions and fatty-acid conjugation can significantly prolong their half-lives, enabling, for example, once weekly dosing. This study revisits the systemic pharmacokinetics of peptide drugs using classical pharmacokinetic principles and elucidates the scaling of peptide pharmacokinetics across species.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown both protective and adverse effects on ocular outcomes. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA, achieves greater glycemic and cardiometabolic improvements than non-GIP agonistic GLP-1RAs, yet its ocular safety profile remains poorly characterized.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP1-RA) have potent glucose-lowering and weight loss benefits, but their effects on bone remain unclear.

Abstract

Tirzepatide, a first-class dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a breakthrough in the management of type 2 diabetes and obesity. Given its recent approval and expanding clinical applications, the development of accurate, sensitive, and efficient analytical methods for its determination in pharmaceutical formulations and biological matrices is critically important. In this study, a novel and efficient analytical probe was developed for the selective and sensitive determination of tirzepatide in pharmaceutical dosage form and spiked plasma. Acriflavine was employed as a fluorescent probe due to its strong native fluorescence, excellent stability, and high sensitivity to molecular interactions. The method was based on the formation of a stable 1:1 acriflavine-tirzepatide complex at pH 8.0, resulting in static fluorescence quenching measured at 505 nm following excitation at 451 nm. Validation in accordance with ICH guidelines confirmed the method's excellent linearity over 0.1-20 μg/mL (r = 0.9999), with a detection limit of 0.012 μg/mL and a quantitation limit of 0.036 μg/mL, alongside outstanding precision (RSD < 1%) and accuracy. Furthermore, greenness assessment using multiple evaluation tools confirmed the environmentally friendly nature of the method, highlighting its suitability for routine quality control, pharmacokinetic studies, and potential application to future GIP/GLP-1-based therapies.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for weight management. Although generally well-tolerated, these agents may alter the pharmacokinetics of concurrently administered medications.

Abstract

Bariatric surgery is the most effective treatment modality for individuals with morbid obesity, providing significant and durable weight loss and comorbidity resolution. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptor agonists have shown promise as weight loss drugs, in addition to their use in the treatment of metabolic disorders. While multimodal weight management is the standard of care for individuals with morbid obesity, the benefit of antecedent GLP-1 therapy prior to bariatric surgery has not been well-studied. The objective of this study is to conduct a clinical trial testing the hypothesis that preoperative treatment with a dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonist enhances preoperative weight loss and decreases tissue inflammation, resulting in improved postoperative outcomes.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve glycemic control, promote weight loss, and enhance cardiovascular outcomes. However, their effects on lean mass in older adults are unclear. This case report describes how GLP-1 RAs influenced body composition in 2 older women.

Abstract

On June 26, 2025, a meeting of the expert working group was held in Moscow. The discussion focused on the personalized approach of tirzepatide («Tirzetta®») and semaglutide («Velgia Eco®») in patients with excess body weight, obesity, and type 2 diabetes. Following the meeting, the objective was set to develop a consensus-based algorithm for prescribing these drugs to ensure their effective use in Russian clinical practice.

Abstract

Psoriasis and obesity often occur together, with up to 50% of patients with psoriasis being classified as obese. This increases systemic inflammation, cardiovascular risk, and disease severity while reducing the efficacy of biologic treatments. Despite this overlap, dermatology lacks obesity-specific guidance. This review evaluates lifestyle, pharmacological (glucagon-like peptide 1 receptor agonists [GLP-1 RAs] and tirzepatide) and surgical strategies, as well as clinic-level algorithms, to inform dermatological practice.

Abstract

The prevalence of obesity continues to rise, with notable increase in stage III obesity in North America. The accumulation of excess adipose tissue can impair health with cardiovascular disease being the leading cause for increased mortality in people with obesity. The chronicity of the condition makes sustainable weight loss and improved health difficult for many with lifestyle changes alone, often necessitating the need for pharmacotherapy and bariatric surgery. Bariatric surgery remains the most efficacious treatment for obesity, despite improved pharmacotherapies. However, its low acceptability and accessibility render it an underutilized treatment. Meanwhile, the use of obesity pharmacotherapy, especially glucagon-like peptide 1 receptor agonists (GLP1RA) has become widespread with significant weight loss and improved health outcomes in randomised control trials. The real-world effectiveness of GLP1RA is hindered by issues including cost and tolerability. This narrative review discusses strategies to improve the effectiveness of pharmacotherapy and bariatric surgery and posits that bariatric surgery will continue to play an important role in obesity treatment in the GLP1RA era.

Abstract

Tirzepatide, a dual GIP/GLP-1 receptor agonist, is highly effective in reducing body weight and improving glucometabolic outcomes. However, most clinical trials have overlooked the role of diet quality, leaving unclear whether lifestyle factors may modulate pharmacological benefits. The Mediterranean diet, assessed through the validated PREDIMED score, has proven effects on visceral adiposity and metabolic health and may act synergistically with novel incretin therapies.

Abstract

We describe a case of euglycemic diabetic ketoacidosis (EDKA) in a 30-year-old man with no known diabetes on tirzepatide, intermittent fasting (IF), and a low-carbohydrate diet for weight loss. While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combined GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GLP-1/GIP RAs), like tirzepatide, are effective for weight loss and diabetes management, their unsupervised use, especially alongside ketosis-inducing diets, may lead to serious risks such as EDKA. This report emphasizes the need for medical supervision in weight management, particularly when combining medications such as tirzepatide with dietary interventions, like IF and low-carbohydrate diets.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of type 2 diabetes, obesity and cardiovascular health, yet some patients remain hesitant to start these therapies due to perceptions that they are "new" or unproven. This commentary equips clinicians with practical counseling strategies to reframe the "newness" narrative and address long-term safety concerns. We provide a brief history of GLP-1 from its discovery in the 1980s to nearly two decades of clinical use, underscoring that GLP-1RAs are the product of extensive research rather than experimental novelties. We compare native GLP-1 to newer agents like semaglutide and tirzepatide, highlighting structural modifications that prolong action without fundamentally altering the hormone's mechanism. Known safety data are summarized emphasizing the predominance of mild, transient gastrointestinal side effects and the lack of evidence for feared risks like cancer along with how to discuss these points. A practical counseling checklist and sample patient-centric language are included to facilitate shared decision-making. In sum, clinicians can confidently reassure patients that GLP-1RAs are well-studied, mechanism-based therapies with millions of patient-years of experience supporting their safety and efficacy.

Abstract

Obesity is a complex, multifactorial disease that contributes to a broad range of cardiometabolic, reproductive, and psychological disorders. Representing a major global health challenge, obesity can be addressed by lifestyle modifications such as reduced calorie intake, physical activity, adequate sleep, and stress management to help achieve sustainable weight loss and improve metabolic health in the long term. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two naturally produced incretin hormones in the gastrointestinal tract. Incretin analogues were initially approved for type 2 diabetes mellitus but were later found to exhibit weight-reducing properties. Liraglutide, semaglutide, and tirzepatide are the three incretin analogues approved for obesity in non-diabetic patients. This narrative review presents detailed comparisons of the three approved incretin analogues for obesity, their cost-effectiveness, and trends in the clinical setting.

Abstract

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have advanced the treatment of type 2 diabetes mellitus (T2DM), yet their association with cancer risk remains subject of ongoing research. Chronic pancreatitis (CP) is a well-established risk factor for pancreatic cancer, yet the impact of GLP-1 RA therapy in this high-risk population is unknown. In this study, we aimed to evaluate the association between GLP-1 RA use and pancreatic cancer incidence among patients with CP, and among those with CP and T2DM. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. In the first analysis, adult patients with pre-existing CP were identified and stratified by use of a GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, lixisenatide, and albiglutide). Propensity score matching (PSM) was conducted between GLP1-RA users and non-users, matching for age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, and pancreatic cysts. Five-year incidence of pancreatic cancer was compared between GLP-1 RA users and non-users in the matched cohort between 2015 and 2025. We then restricted the cohort to patients with CP and T2DM and repeated this analysis. Results: We identified 89,596 patients with CP, including 3183 GLP-1 RA users and 86,413 non-users. After PSM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.30-0.80, p < 0.005). Similarly, amongst patients with CP and T2DM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (HR 0.53, 95% CI 0.31-0.91, p < 0.05). Conclusions: GLP-1 RA use was associated with a significantly reduced incidence of pancreatic cancer in all patients with CP, as well as the subpopulation with both CP and T2DM. Given the elevated cancer risk in CP, these findings suggest a potential beneficial effect of GLP-1RA use in this high-risk population. Prospective studies will be important to further analyze and confirm this potential benefit.

Abstract

Tirzepatide is an anti-obesity drug based on dual agonism of the incretin receptors GLP-1R and GIPR. Its anti-obesity effect is largely based on its action of reducing food intake. However, there are indications that tirzepatide exerts effects on adipose tissues beyond those resulting from fat loss due to reduced food intake. To investigate this, we treated mice, previously been made obese through high-fat diet, with tirzepatide. We also established an experimental group of mice pair-fed with those treated with tirzepatide, key to distinguish the specific effect of tirzepatide from food intake reduction-mediated effects. Both groups experienced similar reduction in body weight, with a trend toward greater loss in visceral and subcutaneous white fat in mice under tirzepatide treatment. Glucose tolerance improved in tirzepatide-treated obese mice, independently of reduced food intake. Tirzepatide treatment also lowered the inflammatory status of obese mice, which in this case, was attributable to decreased food consumption. Tirzepatide exerted distinct effects on brown adipose tissue relative to white adipose tissues, significantly boosting thermogenic activity and modifying its gene expression pattern, including the upregulation of genes linked to thermogenesis and substrate oxidation. White adipose tissues responded differently, being primarily affected in their lipid metabolism. These effects were specific to tirzepatide treatment and not attributable to reduced food intake. Our results indicate that tirzepatide affects the function and metabolism of adipose tissues and especially induces activation of brown adipose tissue in mice, which may be relevant for future human studies to ascertain the mechanisms of tirzepatide metabolic benefits.

Abstract

To explore the association of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on heart rate (HR) in overweight or obese patients without diabetes.

Abstract

Gastric inhibitory polypeptide (GIP)/Glucagon-like peptide-1 (GLP-1) receptor agonists are increasingly prescribed for the management of obesity and type 2 diabetes, yet research pertinent to their effects on muscle health is limited. Considering the central role of muscle strength as a sarcopenia component, this article summarizes emerging evidence on insulin-based therapies and muscle strength. Short-to-mid-term trials of semaglutide or liraglutide in adults with obesity have shown statistically preserved handgrip strength despite reductions in lean soft tissue mass, suggesting that muscle strength may not decline proportionally to weight loss. Likewise, tirzepatide combined with resistance and aerobic training in young men may not confer additional strength benefits beyond exercise alone. In contrast, longitudinal and retrospective research in older adults with type 2 diabetes have reported reductions in handgrip strength and accelerated sarcopenia with prolonged semaglutide use, raising concerns about potentially detrimental effects on neuromuscular health. Collectively, these findings indicate that lean soft tissue loss is not a reliable predictor of muscle strength change following GIP/GLP-1 agonists. While shorter term studies suggest relative preservation, longer term data in older adults point to possible risk of muscle strength decline. Future randomized, double-blinded trials with adequate sample sizes and longer follow-ups are warranted, particularly in older populations who are at an increased risk of sarcopenia. Their findings could support the integration of muscle strength outcomes into clinical monitoring and trial design to ensure that GIP/GLP-1 agonist-based strategies may not compromise muscle strength in these populations during weight loss.

Abstract

The glucagon-like peptide-1 receptor (GLP-1R) is a major therapeutic target for type 2 diabetes and obesity. Agonists showing bias in favour of G protein signalling over β-arrestin recruitment and GLP-1R internalisation, e.g. tirzepatide and orforglipron, have favourable clinical efficacy profiles. However, understanding of the effects of biased agonism has been hampered by differences in ligand properties such as affinity, efficacy, stability and pharmacokinetics. Here we used GLP-1R C-tail mutations that inhibit phosphorylation to mimic G protein-biased GLP-1R agonism without the need for ligand modifications.

Abstract

Tirzepatide, a dual GIP/GLP-1 receptor agonist, offers a novel cardiometabolic strategy beyond glycemic control with important implications for heart failure care. By producing potent, sustained weight reduction and favourable changes in lipids, blood pressure, systemic inflammation and endothelial biology, tirzepatide targets central pathophysiologic drivers of obesity-related HFpEF.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RA) such as semaglutide, liraglutide and tirzepatide are effective for obesity and type 2 diabetes mellitus (T2DM) but may predispose users to micronutrient deficiencies through appetite suppression, delayed gastric emptying and altered absorption. Given the rapid rise in GLP-1RA use, clarifying their nutritional impact is clinically important. We conducted a structured search of PubMed and the Cochrane Database (January 2019-May 2025) for adult studies evaluating nutritional or micronutrient outcomes during GLP-1RA therapy. Paediatric studies, those lacking nutrient endpoints, and review articles were excluded. Methods followed SANRA and PRISMA-ScR guidance, and data were synthesised descriptively. Six studies met the inclusion criteria, encompassing 480 825 adults. Vitamin D deficiency was the most common abnormality, occurring in 7.5% at 6 months and 13.6% at 12 months. Iron depletion was frequent, with GLP-1RA users demonstrating 26%-30% lower ferritin levels than SGLT2 inhibitor comparators. More than 60% of users consumed below estimated requirements for calcium and iron, and vitamin D intake averaged 20% of recommendations. Protein and calcium insufficiency contributed to lean mass loss, while thiamine and cobalamin deficits increased over time. GLP-1RA therapy is associated with meaningful nutritional deficiencies. Targeted nutritional assessment and individualised laboratory evaluation may be appropriate for patients at increased risk of malnutrition. Findings are mainly derived from observational datasets, and causality between GLP-1RA therapy and nutritional deficiencies cannot be definitively established.

Abstract

Dual and triple incretin-based therapies are transforming treatment for type 2 diabetes mellitus, obesity, and non-alcoholic fatty liver disease. By targeting glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon receptors, these agents enhance glycemic control, reduce body weight, and improve liver outcomes. Drugs like tirzepatide and retatrutide have shown unprecedented efficacy and tolerability. This review summarizes their mechanisms, clinical progress, and limitations, highlighting how dual and triple incretin agonists may extend or refine the therapeutic benefits established by current GLP-1-based therapies. While challenges remain in safety, accessibility, and long-term use, multi-target agonists represent a promising future in metabolic disease management.

Abstract

Evidence suggests sodium glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists reduce the dementia onset/progression. The dual GLP1/GIP receptor agonist, tirzepatide's effect on dementia outcomes remains unknown. We compared tirzepatide, semaglutide and SGLT2-i head-to-head in relation to incident dementia in type 2 diabetes patients METHODS: Three target trial emulations (TTE) were conducted using real-world data from the TriNetX global federated network: TTE1: tirzepatide vs. SGLT2-i, TTE2: semaglutide vs. SGLT2-i and TTE3: tirzepatide vs. semaglutide. Eligible adults with type 2 diabetes and no baseline dementia were included. Follow-up was two years. First diagnosis of dementia, MACE, and all-cause mortality were analysed using survival analysis after propensity score matching.

Abstract

In 2024, a second brand of injectable semaglutide was marketed, authorized for the indication of weight loss, along with the first tirzepatide. Both are indicated as an adjunct to a low-calorie diet and increased physical activity for weight control, including weight loss and maintenance, in adults with a BMI greater than 27. In Community Pharmacy, we have a Professional Pharmaceutical Service in Nutrition, and it is of interest to study and compare the outcomes obtained by patients using these drugs versus those who only adopt lifestyle changes in diet and physical activity. This is especially relevant after observing that several patients had stopped attending the Nutrition Service, arguing that maintaining diet and increasing physical activity required too much effort, and that they would instead request a prescription for one of these drugs from their primary care physician. A protocol was therefore designed to conduct a research study during 2026 to allow follow-up of patients treated with injectable semaglutide and tirzepatide, since during the dispensing of these medicines it was detected that patients lacked knowledge regarding possible adverse effects and the dietary and physical activity habits they should maintain during treatment. The most frequent adverse effects are gastrointestinal: nausea, vomiting, diarrhea, constipation, abdominal pain; others may also appear such as headache, dizziness, and fatigue, and cases of retinopathy, hypotension, cholelithiasis, and hair loss, among others, have been reported. Data collection will take place during 2026 through various questionnaires and/or interviews with patients who agree to participate in the study. Different questionnaires will be developed to collect important information at each phase of treatment, as well as the outcomes obtained in terms of weight loss and lifestyle habits adopted after initiating pharmacological treatment, in order to perform a statistical analysis of the variables. The main objective of the research will be to assess the results obtained over one year regarding weight loss in patients treated with semaglutide or tirzepatide, as well as adverse effects and, where applicable, rebound effect, and to compare them with the results obtained in other patients from the nutrition service who are not receiving these treatments. With the data obtained, statistical analyses will be carried out to describe the sample, using absolute and relative frequencies for qualitative variables, and means and standard deviations for quantitative ones. Chi-square tests will also be used to compare proportions regarding weight loss, adverse effects, weight maintenance or rebound, and dietary and exercise habits adopted by patients treated with semaglutide or tirzepatide compared with those not using these drugs. In addition, potential DRPs (Drug-Related Problems) and NMOs (Negative Medication Outcomes) will be studied, and health education will be provided, emphasizing the importance of acquiring healthy dietary and physical activity habits.

Abstract

The advent of tirzepatide has transformed obesity care; yet, real-world weight loss outcomes necessarily depend on patient engagement with behavioral support. Digital platforms offering coaching, self-monitoring, and automated feedback have the potential to further augment pharmacological efficacy.

Abstract

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that affects approximately 1% of the population. Second-generation non-sedating H1-antihistamines (H1AH) are considered the first-line treatment; however, a substantial proportion of patients remain refractory and require alternative therapeutic approaches, including anti-IgE antibodies or other agents that inhibit mast cell activation and degranulation. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are widely used for the treatment of type 2 diabetes mellitus and obesity and are known to reduce cardiovascular risk as well as comorbidities such as kidney disease and depression. In addition, GLP-1RAs have been reported to improve several autoimmune and autoinflammatory disorders, including dermatoses such as psoriasis, hidradenitis suppurativa, and atopic dermatitis. Several mechanisms have been proposed to explain the immunomodulatory effects of GLP-1RAs, including their influence on cytokine networks and immune cells, particularly mast cells. We report two female patients, aged 44 and 45 years, with long-standing CSU inadequately controlled on high-dose H1AH, who were initially prescreened for participation in a clinical trial with barzolvolimab. Before trial enrollment, both initiated GLP-1RA therapy (semaglutide or tirzepatide) for metabolic indications. Remarkably, both patients achieved complete resolution of CSU within 3 weeks of GLP-1RA initiation, with remission persisting for over 6 months. These observations suggest a potential immunometabolic mechanism linking GLP-1 signaling and mast cell activation, highlighting a novel therapeutic avenue for antihistamine-resistant CSU.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized the treatment of type 2 diabetes mellitus and obesity in recent years. While gastrointestinal adverse events are common, their association with nutritional deficiencies, including thiamine, has not been comprehensively investigated. This study aimed to evaluate whether treatment with GLP-1 RAs is associated with the occurrence of Wernicke encephalopathy (WE).