🧪 TrialInsufficient
Registered Phase 1 interventional trial (recruiting). Background: Glucagon-like peptide 1 (GLP-1) agonist drugs are used to treat diabetes and aid weight loss. They may also help reduce cravings for drugs and alcohol. Researchers want to know if a GLP-1 drug (tirzepatide) can lessen the urge to drink in people with alcohol use disorder (AUD). Objective: To learn how the brains of people with AUD respond to a GLP-1 drug. Eligibility: People aged 21 to 65 years with AUD who are non-treatment seeking. They must be enrolled in protocol 14-AA-0181. Healthy volunteers are also needed. Design: This s
ClinicalTrials.gov · Apr 2026View trial ↗ InsufficientPreprint
This narrative review examines the pharmacogenomics of GLP-1 receptor agonists — principally semaglutide (Ozempic®/Wegovy®) and the dual GIP/GLP-1 agonist tirzepatide (Mounjaro®/Zepbound®) — with a focus on explaining the wide inter-individual variability in efficacy and tolerability observed in clinical practice. The authors synthesise evidence around key genetic loci, including GLP1R, GIPR, ARRB1, TCF7L2, and MC4R, and highlight a purported April 2026 genome-wide association study (GWAS) conducted by 23andMe (n=27,885) as the largest pharmacogenomic study of GLP-1 therapies to date. The review also surveys the competitive landscape among Novo Nordisk, Eli Lilly, 23andMe Research Institute, and PGxAI, and dedicates substantial attention to South Asian and Indian populations, arguing that their large diabetes burden and undercharacterised pharmacogenomic profiles represent a critical gap. The authors conclude that GLP-1 pharmacogenomics has advanced from exploratory science toward actionable clinical discovery. Limitations include the narrative (non-systematic) design, reliance on a preprint-stage GWAS of uncertain peer-review status, and the absence of prospective clinical validation data for genotype-guided prescribing.
Unknown journal · Apr 2026DOI ↗ 🧪 TrialInsufficient
Registered N/A interventional trial (recruiting). This pilot study will evaluate the feasibility, acceptability, and perceived usefulness of the SWITCH mobile nutrition behavioral intervention among adults receiving GLP-1 receptor agonist therapy for obesity and/or type 2 diabetes. Participants will complete baseline assessments, receive a 6-week app-based nutrition intervention consisting of daily dietary self-monitoring and weekly learning modules, and complete follow-up assessments and a structured interview.
ClinicalTrials.gov · Apr 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 2 interventional trial (recruiting). This is a phase 2 randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of icovamenib in participants with Type 2 Diabetes (T2D) not achieving glycemic targets despite Ozempic-based therapy.
ClinicalTrials.gov · Mar 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 2 interventional trial (recruiting). The primary objective of this study is to determine the efficacy of oral KAI-7535 once daily compared with placebo on percent change in body weight in participants living with obesity or overweight, with at least 1 weight-related comorbidity, without diabetes mellitus. Efficacy in participants with type 2 diabetes mellitus will be evaluated. Safety and tolerability and other weight-related outcomes will be evaluated in both types of participants.
ClinicalTrials.gov · Mar 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 1/Phase 2 interventional trial (recruiting). The purpose of this study is to: * evaluate the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses of ALN-2232 in patients with obesity * evaluate the safety, tolerability, efficacy, PK, and PD of multiple doses of ALN-2232 in patients with obesity * evaluate the safety, tolerability, efficacy, PK, and PD of multiple doses of ALN-2232 co-initiated with tirzepatide in patients with obesity
ClinicalTrials.gov · Mar 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 4 interventional trial (not yet recruiting). SHAPE-ENDO is a single-center, open-label, pilot randomized clinical trial conducted at Hospital Universitari de Bellvitge in Barcelona, Spain. The study will evaluate the feasibility, safety, and acceptability of comparing two treatment strategies in women with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or low-risk endometrioid endometrial cancer and grade III obesity, defined as BMI ≥40 kg/m². Eligible participants will be randomized in a 1:1 ratio to one of two arms. The control arm will undergo standa
ClinicalTrials.gov · Mar 2026View trial ↗ Insufficient
This paper describes a pre-registered protocol for a systematic review and network meta-analysis (NMA) examining the comparative efficacy and safety of GLP-1 receptor agonists (GLP-1 RAs) and novel co-agonists (e.g., dual/triple agonists) for weight loss in adults with overweight or obesity who do not have diabetes. The authors plan to search PubMed, Ovid, and Cochrane CENTRAL for randomized controlled trials (RCTs) comparing these agents against placebo or each other. Trials involving participants with diabetes, specific comorbidities, or prior bariatric surgery will be excluded. The primary outcome is relative change in body weight from baseline at approximately 6 months and 1–1.5 years. Secondary outcomes include absolute weight change, total adverse events, gastrointestinal adverse events, serious adverse events, and death. Frequentist random-effects pairwise and network meta-analyses will be conducted, with treatment rankings generated via the surface under the cumulative ranking curve (SUCRA). Risk of bias will be assessed using the Cochrane RoB 2 tool and the RoB-NMA tool. Importantly, this is a protocol paper only — no data have been collected or analyzed yet — so no results or conclusions about the efficacy or safety of any specific agent are available at this stage.
Systematic reviews · Mar 2026DOI ↗ 🧪 TrialInsufficient
Registered Phase 2 interventional trial (active not recruiting). This study will test olatorepatide (study drug) to determine how safe and effective this drug is and how easily your body can accept this drug without causing side effects, as well as how the drug is processed in the body by participants with overweight or obesity. The study will test how safe and effective the study drug works compared to placebo in people who are overweight or obese but do not have diabetes. The study is looking at: * What side effects the study drug might cause * How much the study drug is in the blood at diff
ClinicalTrials.gov · Feb 2026View trial ↗ 🧪 TrialInsufficient
Registered N/A interventional trial (not yet recruiting). The goal of this clinical trial is to determine whether tirzepatide can reduce atrial fibrillation (AF) burden after catheter ablation in overweight or obese patients with persistent AF. It will also evaluate the effects of tirzepatide on body weight, metabolic risk factors, and clinical outcomes, as well as its safety and tolerability in this population. The main questions it aims to answer are: 1. Does peri-procedural treatment with tirzepatide reduce AF burden at 3 months after de novo catheter ablation, as measured by 7-day continuo
ClinicalTrials.gov · Feb 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 2 interventional trial (not yet recruiting). This phase II trial studies whether adding tirzepatide injections to a levonorgestrel intrauterine device (LNG-IUD) improves pathologic response (absence of cancer cells in tissue samples after treatment) in women with endometrial atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or grade 1 endometrial cancer who are overweight or obese. Endometrial cancer occurrence has continued to rise in the United States. Over half of endometrial cancer cases are thought to be attributable to being overweight and obese, and th
ClinicalTrials.gov · Jan 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 4 interventional trial (recruiting). This study will explore whether tirzepatide is a practical and acceptable treatment for postmenopausal females with a history of hormone receptor-positive breast cancer and obesity. The investigators aim to understand whether participants are willing and able to take this medication once weekly for 6 months and whether it may help improve weight and overall health. There will be monthly check-ins to monitor progress and safety. At the beginning and end of the study, participants will undergo body composition assessments, blood tests and a s
ClinicalTrials.gov · Dec 2025View trial ↗ Insufficient
This exploratory simulation study compared the quality of responses generated by a large language model (GPT-4o) versus standard internet searches (Google) when answering 17 common patient-style questions about GLP-1 receptor agonist (GLP-1RA) therapy for obesity. Questions were selected based on Google Trends data and covered indications, expected treatment course, side effects, and specific risks. Two independent evaluators scored responses using a 5-point Likert scale across six domains: safety, guideline consensus, objectivity, reproducibility, relevance, and explainability. The study found that LLM responses scored significantly higher than internet search results in objectivity and reproducibility, while no significant differences were observed in the remaining four domains. Interrater agreement was high (Gwet AC ≈ 0.879). Qualitatively, LLM responses were noted to lack coverage of emerging clinical issues due to static training data, whereas internet results were more current but often commercially biased and inconsistent. The authors conclude that LLMs may offer a more reliable and objective source of health information for patients, though human oversight and real-time data integration remain important limitations to address. The study is limited by its small, simulated question set and lack of real patient interaction data.
JMIR formative research · Nov 2025DOI ↗ 🧪 TrialInsufficient
Registered N/A interventional trial (completed). Obesity is a chronic condition linked to numerous health risks and affects more than one billion people worldwide. While pharmacological treatments such as incretin-based therapies are available, they may have side effects, are not suitable for all patients, and adherence can be limited. Dietary supplements that influence appetite and satiety may represent an alternative or complementary approach. This study will evaluate whether a dietary supplement containing plant extracts stimulates the intestinal incretin response. The primary focus is the
ClinicalTrials.gov · Nov 2025View trial ↗ Insufficient
The DREAMS-3 trial is a randomized, open-label Phase 3 study designed to compare the efficacy and safety of mazdutide (a glucagon receptor/GLP-1 receptor co-agonist) versus semaglutide (a GLP-1 receptor agonist) in Chinese adults with type 2 diabetes (T2D) and obesity. This publication reports the trial's rationale, design, and baseline characteristics rather than outcome results, as the study is ongoing with an expected completion date in early 2026. A total of 349 participants (mean age 42.4 years; 44.7% male) were randomized 1:1 to either treatment arm for a 32-week active-controlled period followed by a 24-week extension. At baseline, participants had a mean HbA1c of 8.0%, body weight of 90.5 kg, and BMI of 33.0 kg/m². The mean T2D duration was 1.8 years, and approximately 39.5% were on metformin. The primary endpoint is the proportion of participants achieving HbA1c targets. Notably, comorbidities such as metabolic-associated fatty liver disease and gout/hyperuricemia showed strong associations with BMI. As a design and baseline data paper, no efficacy or safety outcomes are yet available, limiting current evidence value.
Contemporary clinical trials · Nov 2025DOI ↗ Insufficient
SYNCHRONIZE™-2 is an ongoing double-blind, randomized, placebo-controlled Phase 3 trial evaluating survodutide — an investigational dual glucagon receptor/GLP-1 receptor agonist — for weight reduction in adults with obesity and type 2 diabetes (T2D). This paper reports only the baseline characteristics of the 752 enrolled participants across 133 sites in 19 countries; efficacy and safety results are not yet available. Participants were randomized 1:1:1 to one of two doses of weekly subcutaneous survodutide or placebo, alongside diet and physical activity guidance. At baseline, the cohort had a mean age of 55.7 years, mean BMI of 36.5 kg/m², mean body weight of 104.1 kg, and mean HbA1c of 7.4%; roughly half were female. Common comorbidities included hypertension (69%), dyslipidaemia (68%), and obstructive sleep apnoea (17%). The geographic distribution included participants from Europe, North America, and East Asia, suggesting reasonable diversity. Primary endpoints are percentage change in body weight and achievement of ≥5% weight loss at Week 76. A key limitation of this publication is that it presents only baseline data — no outcomes are yet reported — so no conclusions about efficacy or safety of survodutide can be drawn from this paper alone.
Diabetes, obesity & metabolism · Nov 2025DOI ↗ 🧪 TrialInsufficient
Registered Phase 1 interventional trial (recruiting). The purpose of this study is to investigate how the duration of fasting and temporary stopping of Glucagon-Like-Peptide 1 (GLP-1) medications affect the amount of food left in the stomach in people using liraglutide (injected), semaglutide (taken by mouth) or semaglutide (injected). The length of participants participation in the study will depend on the type of GLP-1 RA treatment participants are already using.
ClinicalTrials.gov · Nov 2025View trial ↗ Insufficient
This paper reports the baseline characteristics of participants enrolled in SYNCHRONIZE-1, a multinational, randomized, double-blind, placebo-controlled Phase 3 trial evaluating survodutide — a dual glucagon receptor and GLP-1 receptor agonist — for weight management in adults with obesity but without type 2 diabetes. A total of 725 participants from 14 countries were randomized 1:1:1 to receive once-weekly subcutaneous injections of survodutide (up-titrated to 3.6 mg or 6.0 mg) or placebo over 76 weeks. At baseline, participants had a mean age of 47.1 years, mean BMI of 37.9 kg/m², and mean waist circumference of 115.2 cm; 59.4% were female. Common obesity-related complications included hypertension (40.0%), dyslipidaemia (33.7%), and prediabetes (30.2%). The primary endpoints are percent body weight change and achievement of ≥5% body weight reduction from baseline to Week 76. As this publication covers only baseline data, no efficacy or safety outcomes are yet reported. The study's key limitation at this stage is that it describes enrollment characteristics only, with no outcome data available.
Diabetes, obesity & metabolism · Nov 2025DOI ↗ 🧪 TrialInsufficient
Registered observational trial (terminated). This study is designed to compare weight loss outcomes and safety of ESG versus lifestyle modification in patients with obesity who discontinued GLP-1 therapy due to intolerance or suboptimal weight loss.
ClinicalTrials.gov · Sep 2025View trial ↗ 🧪 TrialInsufficient
Registered Phase 2 interventional trial (recruiting). This study will explore the use of glucagon-like peptide 1 receptor agonist (GLP-1RA) used concurrently with levonorgestrel intrauterine device in patients with poor surgical candidacy for a hysterectomy or patients who are pursuing fertility sparing. GLP-1RA are a class of medications that mimic the natural hormone glucagon-like peptide-1. These medications trigger the pancreas to release insulin which can help lower blood sugar levels and delay gastric emptying. The recent FDA approval of GLP-1RAs has changed the landscape for pharmacothe
ClinicalTrials.gov · Aug 2025View trial ↗