Safety, Tolerability and Efficacy of Semaglutide Depot in Subjects With Type-2 Diabetes Mellitus

A Prospective, Multicenter, Open Label, Dose Escalation Phase I/IIa Study to Assess the Safety, Tolerability and Efficacy of Semaglutide Depot in Subjects With Type-2 Diabetes Mellitus

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is an approved and well-established therapy for type 2 diabetes mellitus (T2DM), providing both robust glycemic control and weight reduction. Semaglutide Depot, is a long-acting formulation of semaglutide, designed for once every four weeks administration, intended to reduce treatment burden, and improve adherence supporting sustained glycemic control over time.

This Phase I/Ila dose escalation study design to evaluate the safety, tolerability, pharmacokinetics and efficacy of Semaglutide Depot in adults with T2DM.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabete Type 2
• Intervention / Treatment: Drug: SG Depot 2 mg; Drug: SG Depot 4 mg; Drug: SG Depot 6 mg; Drug: SG Depot 8 mg

Detailed Description

Study Title:

A Prospective, Multicenter, Open-Label, Dose Escalation Phase I/Ila Study to Assess the Safety, Tolerability, and Efficacy of Semaglutide Depot in Subjects with Type 2 Diabetes Mellitus

Background:

Type 2 diabetes mellitus (T2DM) is a chronic condition in which the body cannot properly use insulin, leading to elevated blood glucose levels. It is often associated with overweight or obesity and can lead to serious complications if not well controlled.

Semaglutide, is a GLP 1 receptor agonist, that helps lower blood glucose by increasing insulin secretion, reducing glucagon (a hormone that raises blood glucose), slowing gastric emptying, and reducing appetite. In addition to improving glycemic control, it also supports weight loss and has demonstrated cardiovascular benefits. Semaglutide is already approved in several formulations (examples: Ozempic® for type 2 diabetes and Wegovy® for weight management), but these require once-weekly injections.

Semaglutide Depot (SG Depot) is a new, long-acting formulation developed by Mapi Pharma Ltd. It is designed to be injected once every 4 weeks (once monthly), which may make treatment easier and improve adherence for people with diabetes.

Study Design:

• Type: Phase I/Ila, open label, dose escalation study, prospective study
• Sponsor: Mapi Pharma Ltd., Ness Ziona, Israel
• Sites: Tel Aviv, Israel
• Participants: Up to 24 adults with type 2 diabetes
• Groups: Participants will be divided into 4 sequential dose cohorts: 2 mg, 4 mg, 6 mg and 8 mg
• Dose escalation: will be allowed only after review of safety data

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Roy Eldor, Professor; Phone Number: 972-36974243; Email: roye@tlvmc.gov.il

Study Locations

• Israel
  • Tel Aviv, Israel, 6423906
    • Mapi pharma Investigational Site ISR001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults aged 18-64 years with T2DM, BMI 25-35 kg/m2
2. On stable Semaglutide 1 mg weekly and for at least 3 months
3. HbA1c <8%, eGFR≥60 ml/minute
4. For women: either non-childbearing potential or agreement to use acceptable contraception

Exclusion Criteria:

1. Participation in another investigational drug clinical study within 3 months
2. History of cardiovascular or cerebrovascular disease
3. Neuropathy or retinopathy or macular edema necessitating medical treatment
4. Type 1 diabetes
5. Unstable weight (> 5% change in the last 3 months)
6. Current use of insulin and /or sulfonylureas and/or glinides
7. Known contraindications to Semaglutide (per FDA-approved Semaglutide label)
8. Recent immunosuppressive therapy (within 90 days) or chemotherapy for malignancy within 5 years
9. Moderate or severe hepatic impairment, (ALT or AST> 2 x upper limit of normal (ULN)
10. Severe hypertriglyceridemia (triglycerides >500 mg/dl)
11. Pregnant or breast feeding
12. Any condition that may increase risk or interfere with study participation (per Investigator judgement)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - SG Depot 2 mg	Drug: SG Depot 2 mg; 2 mg administered subcutaneously (s.c., under the skin) once every 4 weeks
Experimental: Cohort 2 - SG Depot 4 mg	Drug: SG Depot 4 mg; 4 mg administered subcutaneously (s.c., under the skin) once every 4 weeks
Experimental: Cohort 3 - SG Depot 6 mg	Drug: SG Depot 6 mg; 6 mg administered subcutaneously (s.c., under the skin) once every 4 weeks
Experimental: Cohort 4 - SG Depot 8 mg	Drug: SG Depot 8 mg; 8 mg administered subcutaneously (s.c., under the skin) once every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The rate of treatment-associated adverse events (AEs)	Through study completion, up to 28 weeks for each subject
Plasma concentration of semaglutide	Through study completion, up to 28 weeks for each subject

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in HbA1c	Baseline (week 0), week 12
Change in fasting plasma glucose from baseline	Baseline (week 0), week 12
Change in body weight from baseline	Baseline (week 0), week 12
The maximal tolerated dose (MTD) of SG Depot	Through study completion, up to 28 weeks for each subject

Collaborators and Investigators

• Sponsor: Mapi Pharma Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: February 4, 2026
• First Submitted That Met QC Criteria: April 29, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Diabetes; Semaglutide Depot; Long-acting semaglutide; SG Depot; semaglutide LAI
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Diabetes Mellitus
• Other Study ID Numbers: SG Depot-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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