Novel Therapy Could Help Patients Keep Weight Off After Stopping GLP-1s

Positive topline results have been announced from a phase 2 study evaluating the efficacy and safety of RDX-002 for lowering triglycerides in adult patients who had recently stopped taking a glucagon-like peptide-1 (GLP-1) receptor agonist, Response Pharmaceuticals said in a release.¹

Novel Therapy Could Help Patients Keep Weight Off After Stopping GLP-1s / Starmapro - stock.adobe.com

RDX-002 is a selective inhibitor of intestinal microsomal triglyceride transfer protein, which reduces the post-meal uptake of both triglycerides and cholesterol. Results from the study (NCT06640972) showed that RDX-002 led to statistically significant reductions in blood fat levels after a high-fat meal and a reduction in weight gain over a 12 week period.

“GLP-1 Receptor Agonist therapies have revolutionized obesity treatment, but they are not the end of the story,” Chris Packard, professor at the University of Glasgow, said in a release.¹ “Many people regain weight and experience the return of an adverse cardiometabolic profile after stopping GLP-1RA therapy. A novel treatment that can sustain and build upon the gains achieved with GLP-1 Receptor Agonists presents a potentially important advance in long-term obesity care.”

The study is a randomized, double-blind, placebo-controlled, parallel-group phase 2 trial evaluating the efficacy and safety of RDX-002 for lowering triglycerides in adult patients who had recently stopped taking a GLP-1, specifically semaglutide or tirzepatide. The study cohort included 68 patients between the ages of 18 and 65 who lost 10% or more or 10 kg of original body weight, and had a HbA1c of less than 6.5% at initial screening. Patients were excluded if they had any diabetes, a recent cardiovascular event, or uncontrolled hypertension.

During the study, patients received either RDX-002 200 mg 2 times each day or placebo for 12 weeks. The primary study outcome was difference in the mean percent change in the incremental postprandial triglyceride area under the curve. Secondary outcomes included change in mean percent of body weight, mean percent change in LDL cholesterol from baseline, and difference in proportion of patients exhibiting at least a 5% body weight increase from baseline.

The study found patients who received RDX-002 had a mean reduction of –227.3 mg*hr/dL in postprandial triglycerides at week 12, compared to +64.1 mg*hr/ml for placebo. After GLP-1 discontinuation, patients receiving the therapy gained less weight and had improved cardiometabolic health markers compared to placebo. RDX-002 was also seen to have a favorable safety profile, with most adverse events being mild to moderate gastrointestinal that resolved early in the treatment period.

Response said in the release that full data from the study will be presented at an upcoming conference. The company also said it plans to evaluate the efficacy and safety of RDX-002 in other weight management indications, including antipsychotic-induced weight gain, as well as in settings in combination with GLP-1s where the therapies may work together.

“These phase 2 results underscore the potential of our approach to address the most critical gap in obesity care following GLP-1 therapy,” Eric Keller, CEO of Response Pharmaceuticals, said in a release.¹ “By targeting key pathways involved in metabolic regulation, we aim to provide a durable, well-tolerated solution that supports long-term weight management and cardiometabolic health.”

READ MORE: Obesity Management Resource Center

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References

1. Response Pharmaceuticals announces positive top-line results from phase 2 study of rdx-002 in post-glp-1 management. News Release. Response Pharmaceuticals. August 13, 2025. Accessed August 14, 2025. https://www.businesswire.com/news/home/20250813869741/en/Response-Pharmaceuticals-Announces-Positive-Top-Line-Results-From-Phase-2-Study-of-RDX-002-in-Post-GLP-1-Management