A Study to Evaluate the Efficacy and Safety of Once-Weekly MET097 in Adults With Obesity or Overweight and T2DM (VESPER-2)

A Phase 2b, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Once-Weekly MET097 in Adults With Obesity or Overweight, and Type 2 Diabetes Mellitus (VESPER-2)

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus (T2DM); Obesity in Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: MET097 Injection

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 11 weeks after administration of the last dose of study treatment.

• Study Type: Interventional
• Enrollment (Actual): 133
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Bessemer, Alabama, United States, 35022
      • KUR Research
  • California
    • Chula Vista, California, United States, 91911
      • ProSciento, Inc.
    • Glendale, California, United States, 91204
      • Michael Roberts Opthamologist (Eye Exam)
    • Long Beach, California, United States, 90807
      • Eye Treatment Center
    • Los Alamitos, California, United States, 90720
      • Collaborative Neuroscience Research, LLC
    • Los Angeles, California, United States, 90017
      • Velocity Clinical Research, Los Angeles
    • Riverside, California, United States, 92506
      • Clinical Innovations, Inc dba CITrials
  • Florida
    • Bradenton, Florida, United States, 34209
      • Synergy Healthcare
    • Hollywood, Florida, United States, 33024
      • Research Centers of America
    • Hollywood, Florida, United States, 33024
      • Miami Eye Institute
    • Tampa, Florida, United States, 33613
      • ForCare Clinical Research
  • Georgia
    • Decatur, Georgia, United States, 30030
      • CenExel iResearch, LLC
    • Riverdale, Georgia, United States, 30274
      • EmVenio Research Centre at PRIME Healthcare
    • Savannah, Georgia, United States, 31405
      • CenExel iResearch, LLC
  • Illinois
    • Morton, Illinois, United States, 61550
      • Koch Family Medicine Clinical Research
    • Naperville, Illinois, United States, 60540
      • Bioluminux Clinical Research
  • Kansas
    • Kansas City, Kansas, United States, 66112
      • EmVenio Research Centre at PRIME Healthcare
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Eagle Eye Care
    • Columbia, Maryland, United States, 21045
      • KUR Research, LLC
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health, LLC.
  • Michigan
    • Garden City, Michigan, United States, 48135
      • EmVenio Research
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Advocare Berlin Medical Associates
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • OnSite Clinical Solutions, LLC
    • Charlotte, North Carolina, United States, 28277
      • Onsite Clinical Solutions, LLC (Satellite site)
  • Texas
    • Farmers Branch, Texas, United States, 75234
      • EmVenio Research Centre at PRIME Healthcare
    • Plano, Texas, United States, 75093
      • Research Your Health
    • Sherman, Texas, United States, 75092
      • Revival Research Institute, LLC

Participation Criteria

Eligibility Criteria

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

Description

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 ketoacidosis, hyperosmolar state/coma, or any other types of diabetes except T2DM)
• 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
• Relevant surgical history including all bariatric or weight loss surgeries
• SGLT2 inhibitors and/or metformin
• Had 1 or more episodes of hypoglycemia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Sterile 0.9% (w/v) saline will be used as placebo treatment during the study.
Experimental: MET097 Active with titration	Drug: MET097 Injection; MET097 is an ultra-long-acting, fully-biased analog of human GLP-1.
Experimental: MET097 Active without titration	Drug: MET097 Injection; MET097 is an ultra-long-acting, fully-biased analog of human GLP-1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in body weight at Week 28 (Day 197)	Baseline (Week 0) through Week 28 (Day 197)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Baseline (Week 0) through Week 39 (Day 274)
Occurrence of hypoglycemia according to American Diabetes Association classifications [ADA 2024]		Baseline (Week 0) through Week 39 (Day 274)
Occurrence of anti-drug antibodies		Baseline (Week 0) through Week 39 (Day 274)
Change from baseline in serum albumin		Baseline (Week 0) through Week 39 (Day 274)
Change from baseline in transthyretin [pre-albumin]		Baseline (Week 0) through Week 39 (Day 274)
Change from baseline in high-sensitivity C-reactive Protein [hsCRP]		Baseline (Week 0) through Week 39 (Day 274)
Characterize the minimum observed concentration (Cmin)		Baseline (Week 0) through Week 39 (Day 274)
Characterize the maximum observed concentration (Cmax)		Baseline (Week 0) through Week 39 (Day 274)
Characterize the area under the concentration versus time curve (AUC)		Baseline (Week 0) through Week 39 (Day 274)
Characterize the time to maximum concentration (Tmax)		Baseline (Week 0) through Week 39 (Day 274)

Collaborators and Investigators

• Sponsor: Metsera, a wholly owned subsidiary of Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2025
• Primary Completion (Actual): January 2, 2026
• Study Completion (Actual): March 18, 2026

Study Registration Dates

• First Submitted: March 13, 2025
• First Submitted That Met QC Criteria: March 20, 2025
• First Posted (Actual): March 26, 2025

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; GLP-1; Overweight; Weight Loss; T2DM; Metsera
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Body Weight Changes; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Weight Loss; Diabetes Mellitus, Type 2
• Other Study ID Numbers: VESPER-2 (MET097-24-202); C6491005 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

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