Obesity Complicating Type 1 Diabetes: GLP-1 Analogue Anti-obesity Treatment

NCT06411210 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 20000354521R01DK134398-01A1
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

More than 40% of young adults with type 1 diabetes (T1D) also have overweight or obesity. Each of these diagnoses increase the risk of adverse cardiovascular events. GLP-1 analogues are anti-obesity medications that are cardioprotective in adults with type 2 diabetes, however evaluation of these agents in people with T1D has been limited to glycemic outcomes. Investigators aim to study the impact of GLP-1 analogue obesity treatment on markers of cardiometabolic risk in young adults with T1D and obesity.

Conditions

Diabetes type1; Obesity

Outcome Measures

Primary Outcomes (3)

• Change in VAT/(VAT+SAT) from baseline to 12 months

  Measured as VAT/Subcutaneous Adipose Tissue + VAT changes over 1 year.

  baseline and 12 months

• Change in hepatic insulin resistance from baseline to 12 months

  Hepatic insulin resistance, measured by serum concentration of beta-hydroxybutyrate (surrogate marker of acetyl-CoA, which regulates gluconeogenesis), changes over 1 year.

  baseline and 12 months

• Change in triglycerides from baseline to 12 months

  Change in triglycerides after a high-fat mixed meal tolerance test, expressed as the total Area Under the Curve (AUCTG) over 6 hours from baseline to 1 year.

  baseline and 12 months

Secondary Outcomes (7)

• Change in weight from baseline to 12 months

  baseline and 12 months

• Change in percent body fat from baseline to 12 months

  baseline and 12 months

• Change in BMI from baseline to 12 months

  baseline and 12 months

• Change in mean glucose concentration

  baseline and 12 months

• Mean time in normal glucose range

  baseline and 12 months

Study Arms (2)

Semaglutide

EXPERIMENTAL

Participants in this arm will receive semaglutide (escalated to 2.4mg or max tolerated dose) weekly for 12 months. Then a 4 week wean period plus 2 weeks as needed insulin titration.

Drug: Semaglutide Pen Injector

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive a matched placebo weekly for 12 months. Then a 4 week wean period plus 2 weeks as needed insulin titration.

Drug: Placebo

Interventions

Semaglutide Pen Injector DRUG

Escalated to 2.4mg or max tolerated dose

Semaglutide

Placebo DRUG

Matched placebo.

Placebo

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-30 years with T1D whose BMI meets FDA approval criteria for anti-obesity pharmacotherapy (BMI ≥30 kg/m2 alone or BMI ≥27 kg/m2 with a weight-related comorbidity)
• Clinical diagnosis of T1D
• Diabetes duration diagnosed ≥ 12 months ago
• HbA1c ≤10% at screening and within the past 90 days
• Stable reported insulin dosing in the past 90 days (within 15%)
• Stable reported BMI in the past 90 days (within 5%)
• Ability to provide written informed consent before any trial-related activities
• Use of real-time continuous glucose monitoring and planned continued use
• Females and males of childbearing potential willing to use highly effective methods of contraception for at least 1 month prior to randomization and agreement to use such a method during study participation and for 2 months after the last dose of study medication administration: Combined estrogen-progestogen contraception including: oral, intravaginal, transdermal (patch), Progestogen-only contraception: oral, injectable or implantable, Placement of an intrauterine device or intrauterine system, Bilateral tubal occlusion (fallopian tubes are blocked), Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate), or Complete sexual abstinence from male-female sex)
• Stated willingness to comply with all study procedures, medication regimen, and availability for the duration of the study
• Participants cannot be randomized if any laboratory safety parameter at screening is outside the below extended laboratory ranges. For randomization, participants should have
• Creatinine \<1.0mg
• Triglycerides (\<400 mg/dl)
• ALT \<3.5 times the upper normal limit (UNL)

You may not qualify if:

• Use of adjunctive diabetes therapies or anti-obesity medications (including any GLP-1 agonist) currently or within the past 6 months.
• Insulin dosing \<0.5 units/kg/day
• Current psychiatric conditions impacting weight, including known eating disorders
• Contraindications to study medications, including:
• Personal history of pancreatitis, renal impairment, or known liver disease other than non-alcoholic hepatic steatosis
• Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia Type 2
• Known or suspected allergy to semaglutide, excipients, or related products.
• Use of lipid lowering medications other than statins and omega-3 products
• Previous randomization in this trial. Participants who enrolled but did not randomize can be re-screened. Potential reasons for enrolment without randomization include scheduling conflicts for the baseline studies, or for females, not yet meeting the highly effective methods of contraception criteria.
• Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures
• Diabetic ketoacidosis in the past 6 months
• Not meeting MRI safety criteria or claustrophobia preventing participation in the MRI
• Anemia or known hematologic condition impacting HbA1c reading, or another medical condition that precludes participation.
• Treatment with another investigational drug or other intervention within the past 1 month
• Subjects with a PHQ-9 score \>15 or those found to have a lifetime history of suicide attempts, or suicidal ideation within the past 3 months on the C-SSRS

Sponsors & Collaborators

• Yale University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Novo Nordisk A/S: collaborator

Study Sites (1)

Yale Pediatric Diabetes Center, Adult and Children's Progam

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michelle Van Name, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rehema Mtawali

CONTACT

203-785-7455; rehema.mtawali@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 13, 2024
• Study Start: July 16, 2024
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)