A Study to Evaluate the Efficacy and Safety of Once-Weekly MET097 in Adults With Obesity or Overweight and T2DM

Phase 2

Recruiting

• Conditions: Obesity in Diabetes; Type 2 Diabetes Mellitus (T2DM)
• Interventions: Drug: MET097 Injection; Drug: Placebo

• Registration Number: NCT06897202
• Lead Sponsor: Metsera

Brief Summary

This study is designed to test how well once-weekly MET097 (an ultra-long-acting GLP-1 receptor agonist) works to treat adults with obesity or overweight and type 2 diabetes mellitus (T2DM) compared to placebo. MET097 or placebo will be administered to individuals via subcutaneous injection once weekly for 28 weeks. If an individual is randomly assigned to MET097 they will receive one of four different dose regimens.

Detailed Description

This is a 28-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to investigate the efficacy, safety, and tolerability of four different once-weekly MET097 dosing regimens vs. placebo for body weight loss in adults (18-75 years of age) with obesity or overweight (body mass index \[BMI\] ≥27 to ≤50 kg/m2) and T2DM . After completing 28 weeks of study treatment, all participants will be followed for approximately 4 weeks after administration of the last dose of study treatment.

Study Timeline

• Study First Submitted: 2025-03-13
• Study Start: 2025-03-14
• Study First Submitted QC: 2025-03-20
• Study First Posted: 2025-03-26
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-10
• Primary Completion: 2026-04
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 125

Inclusion Criteria

• BMI ≥27.0 kg/m2 to ≤50.0 kg/m2 at screening
• Type 2 diabetes mellitus (*T2DM) for at least 3 months before screening
• Glycated hemoglobin (HbA1c) value between ≥7.0% (53.0 mmol/mol) and ≤10.5% (91.3 mmol/mol) at Screening and treated with stable therapy for at least 30 days prior to Screening/Visit 1 (diet and exercise alone or in combination with metformin monotherapy and/or SGLT-2)
• Stable body weight (increase or decrease ≤5 kg) within 3 months prior to screening

Exclusion Criteria

• Female who is lactating or who is pregnant
• Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2
• Fasting triglycerides ≥ 5.6 mmol/L (≥500 mg/dL)
• Poorly controlled hypertension
• History of stroke
• Significant cardiovascular disease including but not limited to unstable angina or valvular heart disease or has a history of myocardial infarction, coronary artery bypass graft, percutaneous coronary artery re-vascularization, or congestive heart failure
• Diagnosis of Type 1 diabetes
• History of acute or chronic pancreatitis
• Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
• History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years
• Diagnosis of Type 1 diabetes
• Relevant surgical history including all bariatric or weight loss surgeries

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MET097 Active with titration	MET097 Injection	-
Placebo	Placebo	-
MET097 Active without titration	MET097 Injection	-

Primary Outcome Measures

Name	Time	Method
Percent change from baseline in body weight at Week 28 (Day 197)	Baseline (Week 0) through Week 28 (Day 197)

Secondary Outcome Measures

Name	Time	Method
Weight reduction (weight loss) from baseline that is ≥ 5%	Baseline (Week 0) through Week 28 (Day 197)
Weight reduction (weight loss) from baseline that is ≥ 10%	Baseline (Week 0) through Week 28 (Day 197)
Weight reduction (weight loss) from baseline that is ≥ 15%	Baseline (Week 0) through Week 28 (Day 197)
Change in glycated hemoglobin A1c (HbA1c)	Baseline (Week 0) through Week 28 (Day 197)
Change from baseline in fasting plasma glucose (FPG)	Baseline (Week 0) through Week 28 (Day 197)
Change from baseline in fasting serum insulin	Baseline (Week 0) through Week 28 (Day 197)
Change from baseline in C-peptide	Baseline (Week 0) through Week 28 (Day 197)
Occurrence of HbA1c <7.0% (53.0 mmol/mol)	Baseline (Week 0) through Week 28 (Day 197)
Occurrence of HbA1c ≤6.5% (47.5 mmol/mol)	Baseline (Week 0) through Week 28 (Day 197)
Occurrence of HbA1c <5.7% (38.8 mmol/mol)	Baseline (Week 0) through Week 28 (Day 197)
Occurrence of treatment-emergent adverse events (TEAEs)	Baseline (Week 0) through Week 31 (Day 220)	Treatment emergent adverse events include adverse events of clinical interest as well as abnormal clinical significant physical exams, laboratory findings, and 12-lead ECG measurements that meet the definition for an AE.
Occurrence of hypoglycemia according to American Diabetes Association classifications [ADA 2024]	Baseline (Week 0) through Week 31 (Day 220)
Occurrence of anti-drug antibodies	Baseline (Week 0) through Week 31 (Day 220)
Change from baseline in serum albumin	Baseline (Week 0) through Week 31 (Day 220)
Change from baseline in transthyretin [pre-albumin]	Baseline (Week 0) through Week 31 (Day 220)
Change from baseline in high-sensitivity C-reactive Protein [hsCRP]	Baseline (Week 0) through Week 31 (Day 220)
Characterize the minimum observed concentration (Cmin)	Baseline (Week 0) through Week 31 (Day 220)
Characterize the maximum observed concentration (Cmax)	Baseline (Week 0) through Week 31 (Day 220)
Characterize the area under the concentration versus time curve (AUC)	Baseline (Week 0) through Week 31 (Day 220)
Characterize the time to maximum concentration (Tmax)	Baseline (Week 0) through Week 31 (Day 220)

Trial Locations

Locations (5)

Research Site 097202-001001; 🇺🇸 Hollywood, Florida, United States

Research Site 097202-001003; 🇺🇸 Tampa, Florida, United States

Research Site 097202-001002; 🇺🇸 Decatur, Georgia, United States

Research Site 097202-001005; 🇺🇸 Savannah, Georgia, United States

Research Site 097202-001010; 🇺🇸 Cincinnati, Ohio, United States