ADJUnct Semaglutide Treatment in Type 1 Diabetes (ADJUST-T1D)

Efficacy and Safety of Once Weekly Semaglutide in Adults With Obesity and Inadequately Controlled Type 1 Diabetes Using Hybrid Closed-Loop System.

The purpose of this study is to assess the use of once weekly semaglutide injection in inadequately controlled obese adults with type 1 diabetes (T1D) using FDA-approved hybrid closed-loop therapies.

Study Overview

• Status: Completed
• Conditions: Obesity; Type 1 Diabetes
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo

Detailed Description

After being informed about the study and potential risks, all patients given written informed consent will undergo a 2-week screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in a double-blind manner using computer generated randomization scheme to receive either semaglutide or placebo (1:1 ratio) for 26 weeks.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center for Diabetes
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes Research Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Harold Schnitzer Diabetes Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For an eligible subject, all inclusion criteria must be answered "yes"

1. Age ≥18 and ≤ 65 years
2. Patients with clinical diagnosis of T1D diagnosed for at least 12 months
3. Patient is on FDA- approved hybrid closed-loop system for ≥ 3 months
4. Willing to use once weekly semaglutide
5. Willing to share devices (HCL system) data uploads
6. HbA1c >7.0% and <10.0%
7. Body mass index ≥30 kg/m2
8. Has current glucagon product to treat severe hypoglycemia
9. Has current ketone meters to check ketones
10. Ability to provide informed consent before any trial-related activities

Exclusion Criteria:

1. Age <18 years and >65 years
2. HbA1c ≤7.0 % or ≥ 10.0% at screening
3. Less than 12 months of insulin treatment
4. Use of unapproved insulin for HCL system. E.g. use of Fiasp in the Tandem Control-IQ system
5. Not willing to share the devices (HCL system) data uploads
6. Non compatible devices (e.g. pump, CGM or smart phones) for data transfer
7. Current use of multiple daily injection or inhaled insulin (Afrezza)
8. Patients with T1D using any glucose lowering medications other than insulin at the time of screening
9. Pregnancy, breast feeding, and positive pregnancy test during screening
10. Women of childbearing age wanting to become pregnant
11. Unwilling to use acceptable contraceptive methods (for both men and women) during the trial period
12. Current use (≥ 2 weeks of continuous use) of any steroidal medication, or anticipated long-term steroidal treatment (>4 weeks continuously), during the study period
13. Use of GLP-1RA or weight loss medications in the past 3 month
14. Clinical diagnosis/history of gastroparesis or gastric motility disorders
15. Serum triglycerides >500 mg/dL
16. Planning for bariatric surgery during the study period
17. eGFR below 45 ml/min/1.73 m^2 using CKD-EPI formula
18. History of severe hypoglycemia in the previous 3 months
19. History of diabetic ketoacidosis requiring hospitalization in the past 3 months
20. History of allergy to any form of insulin, GLP-1RA or its excipients
21. History of any form of pancreatitis
22. History of stroke, myocardial infarction in the past 3 months
23. History of congestive heart failure class III or IV
24. History of acute or chronic liver disease
25. History of malignancy requiring chemotherapy, surgery or radiation in previous 5 years
26. Personal or family history of multiple endocrine neoplasia type 2 (MEN-2) or familial thyroid carcinoma or non-familial medullary thyroid carcinoma
27. Have a pacemaker, metal implants, or aneurysm clips or weigh >330 lbs (exclusion only if doing MRI)
28. Use of investigational drugs within 5 half-lives prior to screening
29. Participation to other intervention trials during the study period
30. Any comorbidities or medical conditions such as severe psychiatric disorder that make a person unfit for the study at the discretion of the investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide; Participants in this group will receive semaglutide once weekly injection in addition to their standard closed-loop therapy	Drug: Semaglutide; Semaglutide up to 1 mg per week in addition to standard closed-loop therapy
Placebo Comparator: Control; Participants in this group will receive placebo once weekly injection in addition to their standard closed-loop therapy	Drug: Placebo; Injection placebo up to 1 mg per week in addition to standard closed-loop therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Adults With T1D Achieving Composite Outcome (CGM-measured Time in Range (TIR)>70% With Time Below Range (TBR) of <4% and Reduction in Body Weight by 5%) at 26 Weeks in the Semaglutide Group Compared to Placebo Group	Primary outcome will be analyzed per statistical analysis plan using intention to treat basis.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	HbA1c will be measured at a central laboratory and change in Hba1c from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.	26 weeks
Change in BMI (Kg/m2)	Change in body mass index (BMI) calculated as kg body weight per meter squared of height from baseline to 26 weeks will be compared by randomization group using an ITT analysis.	26 weeks
Change in Mean Glucose	Mean glucose (mg/dL) will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.	26 weeks
Percent Time Spent in CGM-measured Glucose Range of 70-140 mg/dL (Time in Tight Target Range; TTIR)	Percent of time spent in tight glucose range (70-140 mg/dL) will be obtained by CGM and change in percent time in range from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.	26 weeks
Percent Time Spent in CGM-measured Glucose >180 mg/dL	Percent of time spent in glucose range >180 mg/dL will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.	26 weeks
Percent Time Spent in CGM-measured Glucose >250mg/dL	Percent of time spent in glucose range >250 mg/dL will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.	26 weeks
Percent Time Spent in CGM-measured Glucose <70mg/dL	Percent of time spent in glucose range <70 mg/dL will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.	26 weeks
Change in CGM Measured Glycemic Variability (Coefficient of Variation)	Glucose coefficient of variation (mg/dL) will be obtained by CGM and change in glucose CV from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.	26 weeks
Change in Weight	The change in kg of body weight from baseline to 26 weeks will be compared by randomization group using an ITT analysis.	26 weeks
Severe Hypoglycemia	SH events in number of patients per group	26 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brach D	Change in brachial arterial distensibility between two groups	26 weeks
Change in eGFR	Change in eGFR using CKD-EPI between two groups	26 weeks
Change in LDL-C	Change in LDL-C between two groups	26 weeks
Change in TC	Change in TC between two groups	26 weeks
Change in TG	Change in TG between two groups	26 weeks
Change in HDL-C	Change in HDL-C between two groups	26 weeks
Change in Patient Reported Quality of Life	Patient reported quality of life will be measured using a validated instrument (ADDQOL) and the change in score from baseline to 26 weeks will be compared by randomization group using an ITT analysis.	26 weeks
Proportion of Participants With HbA1c <7%	proportion (N, %) of participants achieving HbA1c <7% between two groups over 26 weeks	26 weeks
Proportion of Participants With HbA1c <7.5%	proportion (N, %) of participants achieving HbA1c <7.5% between two groups over 26 weeks	26 weeks
HbA1c Improvement	HbA1c improvement from baseline to 26 weeks between two groups	26 weeks
HbA1c Improvement of >0.4% From Baseline	proportion of participants with HbA1c improvement of >0.4% from baseline between two groups	26 weeks
Proportion of Participants Achieving TIR >70%	Proportion of participants achieving TIR >70% between two groups over 26 weeks	26 weeks
Proportion of Participants Achieving TITR >50%	Proportion of participants achieving TITR (time in 70-140 mg/dL) >50% between two groups	26 weeks
Proportion of Participants Achieving TIR >80%	Proportion of participants achieving TIR >80% between two groups	26 weeks
Proportion of Participants Achieving TITR >60%	Proportion of participants achieving TITR (time in 70-140 mg/dL) >60% between two groups	26 weeks
Number of TBR<70 Events	Numbers of events of CGM glucose <70 mg/dL lasting for at least 15 minutes between two groups	26 weeks
Number of TBR <54 Events	Numbers of events of CGM glucose <54mg/dL lasting for at least 15 minutes between two groups	26 weeks
Change in Total Daily Dose of Insulin (TDD, Units Per Day and U/Kg/Day)	Change in TDD between two groups	26 weeks
Proportion Achieving Weight Loss ≥5%	Proportion of participants achieving weight loss ≥5% from baseline between two groups	26 weeks
Proportion Achieving Weight Loss ≥10%	Proportion of participants achieving weight loss ≥10% from baseline between two groups	26 weeks
Proportion of Achieving BMI <30 kg/m2	Proportion of participants achieving BMI <30 kg/m2 between two groups	26 weeks
Proportion of Achieving BMI <25 kg/m2	Proportion of participants achieving BMI <25 kg/m2 between two groups	26 weeks
Change in Systolic Blood Pressure (SBP)	change in SBP (mmHg) between two groups	26 weeks
Change in Diastolic Blood Pressure (DBP)	change in DBP (mmHg) between two groups	26 weeks
Change in Pulse Pressure	change in pulse pressure between two groups	26 weeks
Change in Triglyceride/HDL Ratio	Change in triglyceride/HDL ratio between two groups	26 weeks
Change in Carotid Intima Media Thickness (cIMT)	Change in carotid intima media thickness (cIMT) between two groups	26 weeks
Change in Femoral to Carotid Pulse Wave Velocity (m/s)	Change in femoral to carotid pulse wave velocity (m/s) between two groups	26 weeks
Change in Urine Albumin to Creatinine Ratio (ACR)	Change in ACR between two groups	26 weeks
Quality of Life (Diabetes Dependent QOL)	Change in QOL between two groups	26 weeks
Change in CGM Metrics by Daytime vs Nighttime	Change in CGM metrics (TIR, TITR, mean glucose, TBR, TAR >180, SD, CV) by daytime (6 AM to <11 PM) and nighttime (11 PM to <6 AM) between two groups	26 weeks
AID Setting Adjustment	Defined any adjustment in settings by provider or patient per person over the study period by two groups (number of adjustments (N) during trial) between two groups	26 weeks
Change in Basal Insulin Per Day	Change in basal insulin per day (Total basal insulin including autobasal delivery, units per day and U/kg/day) between two groups	26 weeks
Change in Total Boluses Per Day	Change in total boluses per day (frequency of boluses per day) between two groups	26 weeks
Achievement of Primary Outcome and Key Secondary Outcomes by Types of AID Systems	Proportion of participants achieving primary outcome and key secondary glycemic outcomes by types of AID systems	26 weeks
Change in Carbohydrate Intake Per Day (Grams/Day)	Change in Carbohydrate intake per day (grams/day) between two groups	26 weeks
Change in Total Bolus Insulin Per Day	Change in total bolus insulin per day (units per day and U/Kg/day) between two groups	26 weeks
Change in Fib-4 Score	Change in Fib-4 score between two groups	26 weeks
Change in HSI (Hepatic Steatosis Index)	Change in HSI (hepatic steatosis index) between two groups	26 weeks
Change in MRI Measured Pulse Wave Velocity and Longitudinal Strain	Change in MRI measured pulse wave velocity and longitudinal strain between two groups	26 weeks
Proportion With ACR <30 at 26 Weeks	Proportion of participants with ACR <30 at 26 weeks between two groups	26 weeks
Proportion With Change in ACR From >30 to <30	Proportion of participants with change in ACR from >30 to <30 between two groups	26 weeks
Achievement of Primary Outcomes by Baseline BMI (BMI <35 vs >35)	Achievement of primary outcomes by baseline BMI (BMI <35 vs >35)	26 weeks
Achievement of Primary Outcomes by Baseline A1c (A1c <7.5% vs >7.5%)	Achievement of primary outcomes by baseline A1c (A1c <7.5% vs >7.5%)	26 weeks

Collaborators and Investigators

• Sponsor: Viral N. Shah
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Viral N Shah, MD, Indiana University

Publications and helpful links

General Publications

• Shah VN, Akturk HK, Kruger D, Ahmann A, Bhargava A, Bakoyannis G, Pyle L, Snell-Bergeon JK. Semaglutide in Adults with Type 1 Diabetes and Obesity. NEJM Evid. 2025 Aug;4(8):EVIDoa2500173. doi: 10.1056/EVIDoa2500173. Epub 2025 Jun 23.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2023
• Primary Completion (Actual): August 6, 2024
• Study Completion (Actual): August 6, 2024

Study Registration Dates

• First Submitted: August 23, 2022
• First Submitted That Met QC Criteria: September 8, 2022
• First Posted (Actual): September 13, 2022

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; HbA1c; Weight loss; Type 1 diabetes; Cardiovascular risk; Time-in-range
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Autoimmune Diseases; Immune System Diseases; Body Weight Changes; Glucose Metabolism Disorders; Diabetes Mellitus; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Weight Loss; Diabetes Mellitus, Type 1; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; semaglutide
• Other Study ID Numbers: 22388

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD may be available once the study is completed and all results are published.
• IPD Sharing Time Frame: Study protocol is available
• IPD Sharing Access Criteria: Anyone can access the protocol
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No