Effect of Weekly GLP1 Agonist Treatment in "Double Diabetes" (TOLEDDO)

Effect of Weekly GLP1 Agonist Treatment in "Double Diabetes": a Randomized Open-label Study

Between 16% and 22% of type 1 diabetic patients present a clinical and biological profile of insulin resistance favored by a family history of type 2 diabetes or metabolic syndrome. They constitute a group of patients with "double diabetes" since they have both true type 1 diabetes and inherited insulin resistance, typical of type 2 diabetes.

For several years, GLP1 agonists have been successfully used in the treatment of type 2 diabetes, leading to very significant improvements in glycemic control and weight loss.

Because of the insulin-sensitizing power of GLP1 agonists, the investigators hypothesize that they could reduce insulin resistance in patients with "double diabetes" and thus improve their glycemic control.

The investigators propose to use in this study semaglutide, the most recent and most potent GLP1 agonist (superiority demonstrated compared to exenatide LP and dulaglutide) and administered as a weekly subcutaneous injection (in contrast to liraglutide administered daily).

Study Overview

• Status: Recruiting
• Conditions: Double Diabetes
• Intervention / Treatment: Drug: Insulin + semaglutide treatment; Biological: Biological check-up; Drug: Usual insulin treatment

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Benjamin BOUILLET; Phone Number: 03.80.29.34.53; Email: benjamin.bouillet@chu-dijon.fr

Study Locations

• France
  • Dijon, France, 21000
    • Recruiting
    • Chu Dijon Bourgogne
    • Contact: Benjamin BOUILLET; Phone Number: 03.80.29.34.53; Email: benjamin.bouillet@chu-dijon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Person who has given written consent
• Patient over 18 years of age
• Patient with type 1 diabetes confirmed by a C-peptide below laboratory standards
• Age at diagnosis < 35 years
• Treated with optimized insulin therapy (multi-injections or pump) for at least 1 year, having received specific therapeutic education on insulin dose adaptation.
• BMI (weight/height2) ≥ 27 Kg/m².

• At least one of the following criteria:

  • Family history of type 2 diabetes (parents, grandparents, uncles, aunts, brothers and sisters)
  • Family history of obesity (BMI>30 Kg/m2) (parents, grandparents, uncles, aunts, siblings)
  • Triglycerides > 1.50g/l (1.7mmol/l)
  • HDL< 0.5 g/l (1.29 mmol/l) in women, HDL<0.4 g/l (1.03 mmol/l) in men
• HbA1c ≥ 7.5% and < 12% in the 3 months preceding inclusion
• Having continuous glucose monitoring by a CGM (Holter Glucose Monitoring) system: Guardian, Dexcom or Free Style Libre
• For women of childbearing age: using an effective method of contraception until 2 months after the end of treatment. Effective contraception includes: hormonal contraception, intrauterine device, bilateral tubal occlusion, vasectomy and sexual abstinence

Exclusion Criteria:

• person not affiliated to national health insurance
• Pregnant, parturient or breastfeeding woman
• HbA1c ≥12% in the 3 months preceding inclusion.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy, confirmed by a fundus examination performed in the 6 months preceding the selection
• Person under a measure of legal protection (curatorship, guardianship)
• Renal insufficiency (GFR<30 ml/mn)
• Hepatic insufficiency (INR> 1.5)
• BMI >40 kg/m².
• History of bariatric surgery
• History of pancreatitis
• Allergy to the active substance or to one of the excipients of OZEMPIC®.
• Patients treated with GLP1 agonists or oral antidiabetics in the month preceding month prior to inclusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide	Drug: Insulin + semaglutide treatment; Usual insulin treatment + semaglutide (0.25 mg/week for 4 weeks, then 0.50 mg/week for 4 weeks, then 1 mg/week for 18 weeks, i.e. a total duration of 26 weeks). Upon introduction of semaglutide (ozempic) treatment, insulin doses will be reduced by 10% (basal insulin, basal rate and bolus); Biological: Biological check-up; at D0, D90 and D180
Active Comparator: Control	Biological: Biological check-up; at D0, D90 and D180; Drug: Usual insulin treatment; Usual insulin treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of time spent within glycemic target range (0.70-1.80 g/l)	Change from baseline at Day 180

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: March 9, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Estimated): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulins; Pancreatic Hormones; Proinsulin; Insulin
• Other Study ID Numbers: BOUILLET PHRCI 2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No