Animal only
This pre-clinical study investigated whether retatrutide (RETA, LY3437943) — a triple incretin agonist targeting GIP, GLP-1, and glucagon receptors — could reduce obesity-associated cancer progression beyond its known weight-loss effects. Using mouse models, researchers found that RETA-induced weight loss was associated with reduced pancreatic cancer engraftment, delayed tumor onset, and a 14-fold reduction in tumor volume compared to controls, outperforming single-agonist semaglutide (which achieved a 4-fold reduction). In a lung cancer model, RETA was associated with 50% reduced tumor engraftment and a 17-fold reduction in tumor volume. Notably, anti-tumor benefits persisted even after RETA withdrawal and subsequent weight regain, suggesting potential durable immune effects. Proposed mechanisms included systemic immune reprogramming: elevated circulating IL-6, increased antigen-presenting cells, reduced immunosuppressive cells, and activation of pro-inflammatory pathways within the tumor microenvironment. Key limitations include the exclusive use of pre-clinical (mouse) models, meaning findings may not translate directly to humans, and the mechanistic basis of durable immunity requires further investigation. The authors suggest these results warrant clinical exploration of RETA's potential to reduce cancer risk and improve outcomes in patients with obesity.
npj metabolic health and disease · Mar 2025DOI ↗ 🧪 TrialInsufficient
Registered Phase 4 interventional trial (active not recruiting). This study is being done to assess the efficacy of a saliva- based biomarker to predict response to semaglutide for the treatment of obesity.
ClinicalTrials.gov · Feb 2025View trial ↗ Insufficient
This cross-sectional pilot study examined the direct-to-consumer market for compounded glucagon-like peptide-1 (GLP-1) receptor agonists in Colorado. Researchers conducted Google searches of business websites advertising compounded GLP-1 products for weight loss across census-defined statistical areas between March and April 2024. They identified 93 websites corresponding to 188 physical locations. Most businesses were categorized as medical/health spas or weight loss services. Semaglutide was the most commonly advertised product (92/93 sites), followed by tirzepatide (40/93). Some sites advertised combination formulations including B vitamins, BPC-157 (flagged by the FDA as unsafe for compounding), and other additives. Seven sites advertised oral formulations. Notably, 41 of 93 websites referenced FDA approval in their product descriptions—a potentially misleading claim, as compounded products are not FDA-approved—and 5 sites incorrectly referred to products as "generic." The study's limitations include its focus on a single state, reliance on publicly available website data, and its pilot/cross-sectional design, which limits generalizability. The authors conclude that regulatory action is needed to address misleading advertising and safety concerns in this market.
Journal of pharmaceutical policy and practice · Dec 2024DOI ↗ Limited · human
This market surveillance study investigated the quality and safety risks of semaglutide products sold without a prescription through illegal online pharmacies. Researchers analyzed 1,080 links from search engine results pages, identifying 59 unique illegal online pharmacy websites. Web traffic data showed the top 30 affiliated domains accumulated over 4.7 million visits in a three-month period. Test purchases were attempted from six illegal vendors; three injection vials were delivered (three prefilled pens were never delivered, representing e-commerce scams). Visual inspection of the vials revealed noncompliance in 59–63% of evaluated packaging criteria, flagging them as probable substandard or falsified products. Laboratory analysis using liquid chromatography–mass spectrometry found semaglutide content exceeded labeled amounts by 28.56–38.69%, while measured purity was critically low (7.7–14.37%), far below the 99% claimed on labels. Endotoxin contamination was detected in all samples (2.16–8.95 EU/mg), posing a serious injection safety risk. No viable microorganisms were detected at the time of testing. The study's limitations include a small number of purchased samples and a single geographic/time window of surveillance. The authors conclude that unregulated online semaglutide markets present significant public health risks analogous to earlier waves of illicit erectile dysfunction drug sales.
Journal of medical Internet research · Nov 2024DOI ↗ Review
This review article provides a comprehensive overview of approved and emerging hormone-based anti-obesity medications (AOMs), situating them within the broader context of obesity as a complex, chronic, global disease. The authors summarize the current regulatory landscape, noting that the GLP-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide have received FDA and EMA approval for weight management. The review also covers pipeline agents, including oral GLP-1RAs (semaglutide, danuglipron, orforglipron), the amylin receptor agonist cagrilintide (alone and in combination with semaglutide), and dual agonists such as tirzepatide (GIP/GLP-1), survodutide, mazdutide, and pemvidutide (GLP-1R/GCGR). The authors highlight tirzepatide's placebo-subtracted weight reduction of 17.8% in a 72-week RCT and retatrutide's (a GLP-1R/GCGR/GIPR tri-agonist) placebo-subtracted reduction of 22.1% in a 48-week phase-II trial. The review cautions that long-term safety and cardiovascular outcome data for many of these agents remain incomplete. As a narrative review, it does not conduct original research or meta-analysis, and conclusions are limited by the quality and heterogeneity of the underlying primary studies it synthesizes.
Indian journal of endocrinology and metabolism · Sep 2024DOI ↗ Moderate · human
This systematic review and meta-analysis examined the weight-loss efficacy and safety of cagrilintide (an amylin analogue) alone and in combination with semaglutide 2.4 mg (referred to as "Cagrisema") compared to placebo or active comparators (semaglutide or liraglutide) in adults with obesity. Researchers searched electronic databases and identified 3 eligible randomized controlled trials encompassing 430 participants. The pooled analysis found that Cagrisema was associated with significantly greater percentage and absolute body weight reduction compared to semaglutide 2.4 mg alone over 20–32 weeks, though with notably high statistical heterogeneity (I² up to 98%). Cagrilintide monotherapy showed statistically similar weight loss to semaglutide or liraglutide over 26–32 weeks. Regarding safety, treatment-emergent and serious adverse events were broadly comparable across groups; however, gastrointestinal adverse events and vomiting were significantly more frequent with Cagrisema versus semaglutide, while vomiting was significantly lower with cagrilintide monotherapy versus semaglutide or liraglutide. Key limitations include the very small number of included trials (n=3), limited total sample size, short-to-medium follow-up durations, and very high heterogeneity, which tempers confidence in the pooled estimates.
Indian journal of endocrinology and metabolism · Sep 2024DOI ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (active not recruiting). This study will look at how much CagriSema lowers blood sugar and body weight in people with type 2 diabetes. CagriSema is a new investigational medicine. Doctors cannot yet prescribe CagriSema. CagriSema will be compared to a medicine called tirzepatide. Doctors can prescribe tirzepatide in some countries. Participants will either receive CagriSema or tirzepatide. Which treatment the participant will receive is decided by chance. For each participant, the study will last for up to 1 year and 4 months.
ClinicalTrials.gov · Aug 2024View trial ↗ Review
This review article examines the evolving landscape of glucagon-like peptide-1 (GLP-1)-based therapies for obesity management. The authors describe how obesity, a major risk factor for type 2 diabetes and cardiovascular disease, often resists traditional lifestyle interventions, motivating the development of more targeted pharmacological approaches. The review focuses on incretin mimetics — drugs that mimic nutrient-stimulated hormones — which act on G-protein-coupled receptors including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. Specific agents highlighted include semaglutide and tirzepatide, as well as emerging multiagonist compounds such as GLP-1/glucagon and GIP/GLP-1/glucagon receptor co-agonists. The authors argue that glucagon receptor activation in particular represents a meaningful frontier in the field. The review surveys clinical efficacy data, neuroendocrine mechanisms, and signaling pathways underlying these therapies, while also outlining remaining challenges and future research directions. As a narrative review, it synthesizes existing literature rather than presenting original trial data, and does not conduct a formal meta-analysis. Its conclusions are therefore dependent on the quality and selection of the underlying primary studies reviewed.
Endocrinology and metabolism (Seoul, Korea) · Apr 2024DOI ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (active not recruiting). The purpose of this study is to investigate the efficacy and safety of retatrutide compared with semaglutide in participants with Type 2 Diabetes and inadequate glycemic control with metformin with or without sodium-glucose cotransporter-2 inhibitor (SGLT2i). The study will last about 26 months and may include up to 24 visits.
ClinicalTrials.gov · Feb 2024View trial ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (completed). This is a multicenter, randomized, Open-label Phase 3 clinical study comparing the efficacy and safety of IBI362 6 mg OW versus Semalgutide 1 mg OW in obese(BMI≥28kg/m2) early T2D subjects. Subjects will be randomly assigned to IBI362 6 mg and Semalgutide 1 mg groups for 32 weeks (active-controlled treatment period). In the extension period, participants originally on mazdutide were assigned to continue for an additional 24 weeks with mazdutide 9 mg or 6 mg based on whether they achieved the weight-loss target. All study treatment will be ad
ClinicalTrials.gov · Dec 2023View trial ↗ Moderate · human
This Phase II randomised controlled trial evaluated survodutide (BI 456906), a dual glucagon receptor/GLP-1 receptor agonist, across six dose groups compared with placebo and open-label semaglutide (1.0 mg once weekly) in 413 adults with type 2 diabetes on metformin background therapy. Over 16 weeks, survodutide produced dose-dependent reductions in HbA1c and bodyweight. Higher dose groups achieved HbA1c reductions of approximately 17–19 mmol/mol (~1.6–1.7%), broadly comparable to semaglutide (~16 mmol/mol, ~1.5%), while lower doses showed smaller reductions. Bodyweight decreased dose-dependently, with the highest-dose groups producing greater reductions (up to ~8.7%) than semaglutide (~5.3%). Adverse events, predominantly gastrointestinal, were reported in ~78% of survodutide-treated participants versus ~52% in both the placebo and semaglutide groups. Limitations include the relatively short 16-week treatment duration, the open-label (non-blinded) design of the semaglutide comparator arm, and the Phase II exploratory nature of the trial, which was not powered for head-to-head superiority conclusions. The trial was funded by Boehringer Ingelheim.
Diabetologia · Dec 2023DOI ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (active not recruiting). This study will look at how well semaglutide helps children and teenagers losing weight. This will be tested by comparing the effect on body weight in children and teenagers taking semaglutide in comparison to placebo, a "dummy" medicine. In addition to taking the medicine, the child's parent and the child will have talks with study staff about healthy food choices, how to be more physically active and what your child can do to try to lose weight. The child will either get semaglutide or a "dummy" medicine. Which treatment the ch
ClinicalTrials.gov · Feb 2023View trial ↗ 🧪 TrialInsufficient
Registered observational trial (enrolling by invitation). This is an observational, retrospective, cohort study using administrative insurance claims data. The aim of this non-interventional study (NIS) is to compare maternal, fetal and infant outcomes of women exposed to Wegovy during pregnancy to a reference population not exposed to Wegovy, so that participants and healthcare providers can make informed treatment decisions.
ClinicalTrials.gov · Aug 2022View trial ↗ 🧪 TrialLimited · human
Registered Phase 3 interventional trial (completed), with sponsor-posted results. This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to semaglutide taken once a week in people with type 2 diabetes. The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to semaglutide. Participants will either get IcoSema or semaglutide. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe semaglut
ClinicalTrials.gov · Feb 2022View trial ↗ 🧪 TrialInsufficient
Registered Phase 2 interventional trial (active not recruiting). The prevalence of adolescent severe obesity is at an all-time high in the United States and the refractory nature of this disease has led to a serious and challenging conundrum in terms of how to provide effective, safe, scalable, and durable treatments without placing undue strain on the healthcare system. Clinical practice guidelines recommend behavioral interventions as the primary strategy for all ages and classes of obesity - moderate to severe. In 2017, the U.S. Preventive Services Task Force (USPSTF) released updated scree
ClinicalTrials.gov · May 2021View trial ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (active not recruiting). Semaglutide is a medicine studied in patients with NASH. Semaglutide is a well-known medicine, which is already used by doctors to treat type 2 diabetes in many countries. Participants will either get semaglutide or a dummy medicine - which treatment participants get is decided by chance. Participants will need to inject themselves with medicine under the skin. Participants will need to do this once a week. The study will last for about 5 years. Participants will have up to 21 clinic visits and 9 phone calls with the clinical sta
ClinicalTrials.gov · Mar 2021View trial ↗ 🧪 TrialInsufficient
Registered observational trial (completed). The aim of this study is to evaluate whether exposure to semaglutide influences the risk of pancreatic cancer in patients with type 2 diabetes. This is achieved by estimating the risk of pancreatic cancer associated with semaglutide use as compared to use of other non-incretin antidiabetic drugs used at a similar stage as Ozempic® or Rybelsus® in the treatment of type 2 diabetes. A multi-national, non-interventional study based on health care data from Denmark, Sweden, and Norway is conducted covering the period 2018-2023. A cohort study design is us
ClinicalTrials.gov · Oct 2020View trial ↗