Genetics of the Acute Response to Oral Semaglutide

NCT05340868 | Recruiting

• 1 other identifier: APK.002.12.2022
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to investigate the genetic basis of the response to short-term (3 months) orally administered semaglutide treatment, in terms of improving metabolic parameters, including the hormonal response to a standardized meal, and changes in body composition and liver steatosis. In the study, parameters such as fasting and 2-hour glucose during OGTT, HbA1c, body fat mass, body weight, total cholesterol, HDL and LDL, triglycerides, HOMA-IR, Matsuda Index and liver steatosis will be assessed. All the patients will undergo genome-wide genotyping. Moreover, in a subset of participants, muscle and fat biopsies will be performed, before and after the treatment, and liver, muscle and pancreas fat content will be assessed using MRI.

Conditions

PreDiabetes; Prediabetic State; Obesity

Keywords

pharmacogenetics; semaglutide; prediabetes; obesity

Outcome Measures

Primary Outcomes (2)

• Glycemic measures - change in HbA1c (%)

  Investigators will measure the change in HbA1c concentration between Visit 2, Visit 3 and Visit 4 as an index of Semaglutide response, and compare them by genotype at selected loci.

  1 and 3 months

• Body composition - change in body weight (kg)

  Investigators will measure the change in body weight measures between Visit 2, Visit 3 and Visit 4 as an index of Semaglutide response, and compare them by genotype at selected loci.

  1 and 3 months

Secondary Outcomes (4)

• Glycemic measures - change in 2-hour glucose (in mg/dl)

  1 and 3 months

• Glycemic measures - change in fasting glucose (in mg/dl)

  1 and 3 months

• Body composition - change in body fat content (kg)

  1 and 3 months

• Body composition - change in lean body mass content (kg)

  1 and 3 months

Study Arms (1)

Semaglutide (oral)

EXPERIMENTAL

In this study, each participant will receive a regimen of oral semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, for a duration of twelve weeks. The dosage will begin at 3 mg/day for weeks 1-2, gradually increasing to 7 mg/day for weeks 3-4, 14 mg/day for weeks 5-6, 28 mg/day for weeks 7-8, and finally, to 42 mg/day for the last four weeks (weeks 9-12).

Drug: Semaglutide Pill

Interventions

Semaglutide Pill DRUG

Oral semaglutide treatment

Also known as: Rybelsus

Semaglutide (oral)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent was given before any study-related action on the subject.
• Age: 18-65 years old
• Body mass index (BMI) \>30 kg/m2 or \>27 kg/m2 when accompanied by prediabetes, diagnosed according to the criteria of the American Diabetes Association

You may not qualify if:

• Patients diagnosed with a serious chronic disease, including:
• Ischemic heart disease
• Heart failure (NYHA class III-IV)
• Severe renal insufficiency (eGFR \<30 ml/min)
• Severe liver diseases
• Inflammatory bowel disease
• Diabetic gastroparesis
• Cancer - currently or in the last five years prior to screening
• Chronic obstructive pulmonary disease
• History of mental illness, major depression or other severe mental disorders
• Use of any medications with clinically-proven significant weight gain or loss effects
• History of undergoing bariatric surgery or other surgery involving the stomach that could affect the absorption of the study drug (according to the investigator's opinion)
• History of idiopathic acute pancreatitis
• A family or personal history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid cancer
• For women - pregnancy, breastfeeding or planning pregnancy.

Sponsors & Collaborators

• Medical University of Bialystok: lead

Study Sites (1)

Clinical Research Centre, Medical University of Bialystok

Bialystok, Podlaskie Voivodeship, 15-276, Poland

RECRUITING

MeSH Terms

Conditions

Prediabetic State; Obesity

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Lukasz Szczerbinski, MD, PhD

  Clinical Research Centre, Medical University of Bialystok

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lukasz Szczerbinski, MD, PhD

CONTACT

+48858318150; lukasz.szczerbinski@umb.edu.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 22, 2022
• Study Start: September 1, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 26, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data requests can be submitted starting 12 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party.

Locations

PL (1)