ADJUnct Semaglutide Treatment in Type 1 Diabetes
- Registration Number
- NCT05537233
- Lead Sponsor
- Viral N. Shah
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 115
For an eligible subject, all inclusion criteria must be answered "yes"
- Age ≥18 and ≤ 65 years
- Patients with clinical diagnosis of T1D diagnosed for at least 12 months
- Patient is on FDA- approved hybrid closed-loop system for ≥ 3 months
- Willing to use once weekly semaglutide
- Willing to share devices (HCL system) data uploads
- HbA1c >7.0% and <10.0%
- Body mass index ≥30 kg/m2
- Has current glucagon product to treat severe hypoglycemia
- Has current ketone meters to check ketones
- Ability to provide informed consent before any trial-related activities
- Age <18 years and >65 years
- HbA1c ≤7.0 % or ≥ 10.0% at screening
- Less than 12 months of insulin treatment
- Use of unapproved insulin for HCL system. E.g. use of Fiasp in the Tandem Control-IQ system
- Not willing to share the devices (HCL system) data uploads
- Non compatible devices (e.g. pump, CGM or smart phones) for data transfer
- Current use of multiple daily injection or inhaled insulin (Afrezza)
- Patients with T1D using any glucose lowering medications other than insulin at the time of screening
- Pregnancy, breast feeding, and positive pregnancy test during screening
- Women of childbearing age wanting to become pregnant
- Unwilling to use acceptable contraceptive methods (for both men and women) during the trial period
- Current use (≥ 2 weeks of continuous use) of any steroidal medication, or anticipated long-term steroidal treatment (>4 weeks continuously), during the study period
- Use of GLP-1RA or weight loss medications in the past 3 month
- Clinical diagnosis/history of gastroparesis or gastric motility disorders
- Serum triglycerides >500 mg/dL
- Planning for bariatric surgery during the study period
- eGFR below 45 ml/min/1.73 m^2 using CKD-EPI formula
- History of severe hypoglycemia in the previous 3 months
- History of diabetic ketoacidosis requiring hospitalization in the past 3 months
- History of allergy to any form of insulin, GLP-1RA or its excipients
- History of any form of pancreatitis
- History of stroke, myocardial infarction in the past 3 months
- History of congestive heart failure class III or IV
- History of acute or chronic liver disease
- History of malignancy requiring chemotherapy, surgery or radiation in previous 5 years
- Personal or family history of multiple endocrine neoplasia type 2 (MEN-2) or familial thyroid carcinoma or non-familial medullary thyroid carcinoma
- Have a pacemaker, metal implants, or aneurysm clips or weigh >330 lbs (exclusion only if doing MRI)
- Use of investigational drugs within 5 half-lives prior to screening
- Participation to other intervention trials during the study period
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Semaglutide Semaglutide Participants in this group will receive semaglutide once weekly injection in addition to their standard closed-loop therapy Control Placebo Participants in this group will receive placebo once weekly injection in addition to their standard closed-loop therapy
- Primary Outcome Measures
Name Time Method 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 26 weeks The primary endpoint (differences in proportion of patients achieving composite outcomes) will be compared, including the proportion of study participants achieving a reduction in body weight of 5% or more between 4 and 26 weeks and achieving TIR \>70% and TBR of \<4% at 26 weeks. This comparison between the proportion meeting the composite endpoint will be examined while adjusting for pre-specified covariates, baseline A1c and BMI. Baseline A1c is known to affect TIR (better improvement in TIR in those with higher A1c). Similarly, higher BMI may affect weight loss. Therefore, the investigator decided to use these covariates for adjustment. Sustain 7 post hoc analysis suggested that efficacy of semaglutide on glycemic control and weight loss remains the same regardless of baseline age, diabetes duration or sex. Therefore, the investigator did not include those variables in the pre-specified adjustment.
- Secondary Outcome Measures
Name Time Method Change in mean glucose 26 weeks Mean glucose (mg/dL) will be obtained by CGM and change in mean CGM glucose from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.weeks will be compared by randomization group using intention to treat (ITT) analysis.
Percent time spent in CGM-measured glucose <70mg/dL 26 weeks Percent of time spent in glucose range \<70 mg/dL will be obtained by CGM and change in mean CGM glucose from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Change in patient reported quality of life 26 weeks Patient reported quality of life will be measured using a validated instrument (ADDQOL) and the change in score from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Change in weight 26 weeks The change in kg of body weight from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Change in BMI (Kg/m2) 26 weeks Change in body mass index (BMI) calculated as kg body weight per meter squared of height from 4 to 26 weeks will be compared by randomization group using an ITT analysis.
Severe Hypoglycemia and diabetic ketoacidosis events 26 weeks SH and DKA events will be calculated as an event rate per 1,000 persons per year and will be compared between the two treatment groups using Poisson regression with follow-up time as an offset
Change in HbA1c 26 weeks HbA1c will be measured at a central laboratory and change in Hba1c from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Percent time spent in CGM-measured glucose range of 70-140 mg/dL (time in tight target range; TTIR) 26 weeks 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 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Percent time spent in CGM-measured glucose >180 mg/dL 26 weeks Percent of time spent in glucose range \>180 mg/dL will be obtained by CGM and change in mean CGM glucose from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Percent time spent in CGM-measured glucose >250mg/dL 26 weeks Percent of time spent in glucose range \>250 mg/dL will be obtained by CGM and change in mean CGM glucose from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Change in CGM measured glycemic variability (coefficient of variation) 26 weeks Glucose coefficient of variation (mg/dL) will be obtained by CGM and change in glucose CV from 4 weeks to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Trial Locations
- Locations (4)
Iowa Diabetes Research Center
🇺🇸West Des Moines, Iowa, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Harold Schnitzer Diabetes Health Center
🇺🇸Portland, Oregon, United States
Barbara Davis Center for Diabetes
🇺🇸Aurora, Colorado, United States