#1 Clinical Trials Search in Europe

DAPIGLUTIDE

Dapiglutide is an innovative medication currently being investigated in clinical trials for weight management in people with obesity and overweight. This novel drug works as a dual agonist, targeting both Glucagon-like peptide-1 receptor (GLP-1R) and Glucagon-like peptide-2 receptor (GLP-2R). The DREAM trial (Dapiglutide for the Treatment of Obesity) is exploring how different doses of dapiglutide, administered once weekly via subcutaneous injection, compare to placebo in promoting weight loss over 12 weeks. Another study is examining the pharmacokinetics of different concentrations of the drug. These clinical trials represent important steps in understanding dapiglutide’s potential as a new treatment option for those struggling with obesity.

Table of Contents

What is Dapiglutide?

Dapiglutide (also known as ZP7570) is a novel medication being developed for the treatment of obesity and overweight. It belongs to a class of medications called dual receptor agonists, specifically targeting two important hormone receptors in the body[1]. What makes dapiglutide unique is that it works on both Glucagon-like peptide-1 receptor (GLP-1R) and Glucagon-like peptide-2 receptor (GLP-2R) simultaneously[2].

This dual-action approach is relatively new in the field of weight management medications. Most currently available medications for obesity target only one pathway or receptor, but dapiglutide’s ability to influence two related but distinct systems in the body may offer advantages in terms of effectiveness and possibly addressing multiple aspects of obesity[1].

How Does Dapiglutide Work?

Dapiglutide works through a mechanism called GLP-1/GLP-2 receptor agonism[1]. Let’s break down what this means:

  • GLP-1 receptor agonism: GLP-1 (Glucagon-like peptide-1) is a hormone naturally produced in your intestines that helps regulate blood sugar levels, slows stomach emptying, reduces appetite, and can promote weight loss. By activating GLP-1 receptors, dapiglutide mimics and enhances these effects.
  • GLP-2 receptor agonism: GLP-2 (Glucagon-like peptide-2) is another hormone that plays roles in intestinal health, nutrient absorption, and gut barrier function. By targeting GLP-2 receptors, dapiglutide may help improve gut health and potentially reduce inflammation.

This dual-targeting approach is what distinguishes dapiglutide from single-target medications like some other weight loss drugs. The combination of reduced appetite, slower digestion, and potentially improved gut health may contribute to its effectiveness in weight management[1][2].

Conditions Treated with Dapiglutide

Based on the clinical trials information, dapiglutide is being developed primarily for the following conditions:

  • Obesity: The medication is being studied in people with a Body Mass Index (BMI) of 30 kg/m² or higher[1].
  • Overweight: Some trials are including participants with a BMI of 27 kg/m² or higher[2].
  • Inflammation: The medication may also have effects on inflammation, as suggested by some of the trial outcomes measuring inflammatory markers[1].

The clinical trials are specifically looking at how dapiglutide might affect not only body weight but also related health markers such as liver health indicators, blood pressure, heart rate, and inflammation levels. This suggests the medication might have broader health benefits beyond just weight reduction[1].

How Dapiglutide is Administered

Dapiglutide is administered as a subcutaneous injection, which means it’s injected just under the skin. Based on the clinical trial information, the key aspects of its administration include:

  • Injection site: The injections are given in the abdomen (stomach area)[1].
  • Frequency: The medication is administered once weekly in the studied treatment protocols[1].
  • Dosing: Various doses are being studied:
    • In the DREAM trial, doses of 4 mg and 6 mg are being tested[1].
    • Another study is testing a single 7.5 mg dose in different concentrations (10 mg/mL and 25 mg/mL)[2].
  • Titration: The dose is gradually increased to minimize side effects. For example, in the DREAM trial, participants start at 2 mg weekly and then the dose is increased by 2 mg every three weeks until reaching the target dose of 4 mg or 6 mg[1].
  • Self-administration: Patients in the clinical trials are taught to give themselves the injections[1].

The different concentrations being tested (10 mg/mL vs. 25 mg/mL) suggest that researchers are working to optimize how the medication is delivered, possibly to improve convenience or comfort for patients[2].

Effectiveness of Dapiglutide

While the full results of the clinical trials are not provided in the available information, we can see what outcomes the researchers are measuring to determine effectiveness:

Primary outcomes being measured include:

  • Percentage change in body weight from baseline to the end of treatment (12 weeks in the DREAM trial)[1].
  • Pharmacokinetic measures (how the drug moves through the body) in other trials[2].

Secondary and other outcomes include:

  • Significant weight loss thresholds: Proportion of participants achieving weight loss of ≥5%, ≥10%, and ≥15%[1].
  • Changes in BMI (Body Mass Index)[1].
  • Changes in blood pressure (both systolic and diastolic)[1].
  • Changes in resting heart rate[1].
  • Changes in body composition as measured by bioimpedance (a method of estimating body fat and muscle mass)[1].
  • Liver health indicators, including measures of liver steatosis (fat in the liver) and fibrosis (scarring)[1].
  • Inflammation markers in the blood, such as high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6)[1].
  • Gut permeability biomarker (LPS-binding protein), which may indicate how well the intestinal barrier is functioning[1].
  • Quality of life measures, including the 36-Item Short Form Survey and the IWQOL-Lite-CT (Impact of Weight on Quality of Life questionnaire)[1].

These comprehensive measures suggest that researchers are evaluating not just the weight loss potential of dapiglutide but also its broader health effects and impact on patients’ wellbeing[1].

Current Clinical Research

Based on the available information, dapiglutide is currently being studied in clinical trials, including:

  • The DREAM trial (Dapiglutide for the Treatment of Obesity): This is a randomized, double-blind, placebo-controlled, proof-of-concept study. It involves 54 participants with obesity (BMI ≥30 kg/m²) who are randomized to receive dapiglutide 4 mg, dapiglutide 6 mg, or placebo for 12 weeks[1].
  • Pharmacokinetic study: This is an open-label, randomized, parallel-group study comparing two different concentrations of dapiglutide (10 mg/mL and 25 mg/mL) after a single dose of 7.5 mg in participants with overweight or obesity (BMI ≥27.0 kg/m²)[2].

The DREAM trial includes a gastroduodenoscopy sub-study in which some participants undergo procedures to obtain gastric and duodenal (small intestine) biopsies before and after treatment. This suggests researchers are investigating how the medication affects the digestive tract at the tissue level[1].

These studies represent early-phase clinical research (Phase 1 for the pharmacokinetic study), indicating that dapiglutide is still in the developmental stages and not yet approved for general use[1][2].

Safety Profile and Side Effects

The available information doesn’t provide a comprehensive list of observed side effects, but we can gain some insights from the trial designs:

  • Safety monitoring: Both trials include monitoring for adverse events (side effects) as part of their outcomes[1][2].
  • Dose titration: The gradual increase in dose (starting at 2 mg and increasing by 2 mg every three weeks) suggests that starting with higher doses might cause more side effects, which is common with GLP-1 receptor agonists[1].
  • Tolerability considerations: The DREAM trial protocol mentions that “To reduce dropout in cases of low tolerability of the IMP, the investigator can postpone up-titration or down-titrate if judged necessary for participant retention or safety.” This indicates that researchers anticipate some participants might experience side effects that could affect their ability to tolerate higher doses[1].

Based on other medications in the GLP-1 receptor agonist class, potential side effects might include nausea, vomiting, diarrhea, constipation, and abdominal pain. However, the specific side effect profile of dapiglutide, particularly with its dual GLP-1/GLP-2 receptor action, will become clearer as more clinical trial results are published[1][2].

Aspect Details
Drug Name Dapiglutide (also known as ZP7570)
Drug Mechanism Dual GLP-1R/GLP-2R agonist (activates both Glucagon-like peptide-1 and Glucagon-like peptide-2 receptors)
Clinical Trial Names DREAM trial (Dapiglutide for the Treatment of Obesity) and a pharmacokinetic study
Administration Subcutaneous (under the skin) injection, once weekly
Doses Studied DREAM trial: 4 mg and 6 mg (with gradual up-titration)
Pharmacokinetic study: Single 7.5 mg dose at two concentrations (10 mg/mL and 25 mg/mL)
Study Participants DREAM trial: People with BMI ≥30 kg/m²
Pharmacokinetic study: People with BMI ≥27 kg/m²
Treatment Duration DREAM trial: 12 weeks
Pharmacokinetic study: Single dose
Primary Outcomes DREAM trial: Percentage change in body weight
Pharmacokinetic study: Drug concentration profiles (AUC and Cmax)
Secondary Outcomes Weight loss thresholds (≥5%, ≥10%), inflammation markers, gut permeability markers, safety and tolerability
Additional Measurements BMI, blood pressure, heart rate, body composition, liver health assessments, quality of life
Unique Features Dual receptor targeting may provide benefits for both weight loss and gut health/inflammation

FAQ

  • What is dapiglutide and how does it work? Dapiglutide (also known as ZP7570) is a dual GLP-1R/GLP-2R agonist, which means it activates two different receptors in the body. GLP-1 receptor activation is known to reduce appetite, slow stomach emptying, and help regulate blood sugar levels. GLP-2 receptor activation plays a role in intestinal health and may help reduce inflammation. By targeting both receptors, dapiglutide is designed to promote weight loss while potentially offering additional benefits related to gut health and inflammation.
  • How is dapiglutide administered in the clinical trials? In the clinical trials, dapiglutide is administered via subcutaneous (under the skin) injection into the abdomen. In the DREAM trial, participants self-administer the injection once weekly for 12 weeks. The medication is started at a lower dose (2 mg) and gradually increased every three weeks to reduce side effects, eventually reaching either 4 mg or 6 mg depending on the treatment group. In the pharmacokinetic study, a single 7.5 mg dose is administered using two different concentrations (10 mg/mL or 25 mg/mL).
  • What outcomes are researchers measuring in the dapiglutide trials? The primary outcome in the DREAM trial is the percentage change in body weight from baseline to week 12. Secondary outcomes include the proportion of participants achieving at least 5% or 10% weight loss, changes in inflammation markers, and gut permeability markers. Researchers are also measuring additional outcomes like changes in BMI, blood pressure, heart rate, body composition, liver health indicators, and quality of life. In the pharmacokinetic study, researchers are measuring how the drug moves through the body, including how quickly it's absorbed, how high the concentration gets in the blood, and how long it stays in the system.
  • Who can participate in these dapiglutide clinical trials? The DREAM trial is enrolling people with obesity, defined as having a Body Mass Index (BMI) of 30 kg/m² or higher. The pharmacokinetic study is recruiting participants with a BMI of 27 kg/m² or higher, which includes both overweight and obese individuals. Each trial has specific inclusion and exclusion criteria to ensure participant safety and to generate reliable data about how the medication works in the target population.
  • What makes dapiglutide different from other weight loss medications? What distinguishes dapiglutide from many other weight loss medications is its dual action on both GLP-1 and GLP-2 receptors. Most current GLP-1 based medications for weight loss (like semaglutide) target only the GLP-1 receptor. The additional GLP-2 receptor activity of dapiglutide may provide added benefits related to gut health and inflammation reduction, beyond weight loss alone. The DREAM trial is specifically looking at inflammatory markers to better understand these potential benefits. This dual action mechanism represents a novel approach in obesity treatment.

Ongoing Clinical Trials on DAPIGLUTIDE

  • Study on Dapiglutide for Weight Loss in Adults with Obesity

    Not recruiting

    1
    Investigated diseases:
    Investigated drugs:
    Denmark

Glossary

  • Dapiglutide: A dual GLP-1R/GLP-2R agonist medication (also known as ZP7570) being investigated for weight management in people with obesity and overweight.
  • GLP-1R: Glucagon-like peptide-1 receptor. When activated, it helps reduce appetite, slow stomach emptying, and regulate blood sugar levels.
  • GLP-2R: Glucagon-like peptide-2 receptor. When activated, it promotes intestinal health and may have anti-inflammatory effects.
  • Dual agonist: A substance that activates two different receptors in the body, in this case both GLP-1 and GLP-2 receptors.
  • BMI (Body Mass Index): A calculation using height and weight to estimate body fat and categorize weight status. A BMI of 30 kg/m² or higher is classified as obesity.
  • Subcutaneous injection (s.c.): An injection given under the skin, rather than into a muscle or vein.
  • Randomized controlled trial: A study design where participants are randomly assigned to different treatment groups to compare outcomes between interventions.
  • Double-blind: A study design where neither the participants nor the researchers know which treatment each participant is receiving until after the study is completed.
  • Placebo: An inactive substance that looks like the drug being tested but has no therapeutic effect, used to determine if the active drug produces real benefits.
  • Up-titration: The process of gradually increasing medication dose over time to reach the target dose while minimizing side effects.
  • Pharmacokinetics (PK): The study of how drugs move through the body, including absorption, distribution, metabolism, and excretion.
  • LPS-binding protein (LBP): A biomarker used to assess gut permeability, which may indicate how well the intestinal barrier is functioning.
  • Inflammation markers: Substances in the blood that indicate the presence of inflammation in the body, such as high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6).
  • FibroScan®: A non-invasive imaging technique used to assess liver steatosis (fat content) and fibrosis (scarring).
  • Fatty liver index score (FLI): A calculation used to predict the presence of fatty liver disease, with scores ranging from 0-100 (scores >60 indicating likely fatty liver).
  • Fibrosis 4 score (FIB-4): A calculation used to assess the risk of liver fibrosis, with higher scores indicating greater risk of advanced fibrosis.
  • Adverse Events (AEs): Any undesirable experience associated with the use of a medical product in a patient, ranging from mild to severe.
  • Serious Adverse Events (SAEs): Adverse events that result in death, are life-threatening, require hospitalization, cause persistent disability, or have other serious medical consequences.
  • IWQOL-Lite-CT: Impact of Weight on Quality of Life-Lite Clinical Trials Version, a questionnaire that measures how weight affects quality of life.
  • Cmax: Maximum concentration of a drug in the blood after administration, indicating how high the drug level gets.
  • AUC (Area Under the Curve): A measurement of the total exposure to a drug over time, used in pharmacokinetic studies to understand drug absorption and elimination.
  • Half-life: The time it takes for the concentration of a drug in the body to be reduced by half, indicating how long the drug stays in the system.

References

  1. https://clinicaltrials.gov/study/NCT05788601
  2. https://clinicaltrials.gov/study/NCT06758583