Diabete Type 2Phase 4PATHS-T2DNCT07739537
PATHS-T2D: A Recall-by-Genotype Study of Physiologic and Pharmacologic Responses
A Phase 4 study testing Orforglipron in people with Diabete Type 2 and Pharmacogenomic Drug Interaction, run by Massachusetts General Hospital.
Trial summary
This research study aims to learn about how the body responds to food through different genetic pathways and how these responses may change during a short course of orforglipron. Orforglipron is an oral glucagon-like peptide-1 (GLP-1) receptor agonist that was approved by the U.S. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Diabete Type 2, Pharmacogenomic Drug Interaction
- What is being tested?
- Orforglipron
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2026to 30 Sep 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male or non-pregnant female volunteers (Age 18-79)
- Not currently taking more than two home oral antidiabetic agents, with or without a diagnosis of type 2 diabetes
- Able and willing to stop home oral antidiabetic medications for 5 days prior to the start of the study, with approval from healthcare providers
- Able and willing to give informed consent
Who cannot join
- Known contraindication for orforglipron (e.g., Personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia type 2 (MEN 2), allergies to any component)
- Personal history of pancreatitis, gallbladder disease, intestinal malabsorption, severe gastroparesis, gastric outlet obstruction, or other clinically significant gastrointestinal motility disorder
- History of liver disease or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x upper limit of normal
- Estimated glomerular filtration rate (eGFR) < 45 mg/min/1.73m2 per the Modification of Diet in Renal Disease equation
- Active gallbladder disease or cholecystectomy within the past 6 months
- Current use of a strong CYP3A4 inducer (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, rifabutin, or St. John's wort) or ritonavir, cobicistat, cyclosporine, or another strong CYP3A4 inhibitor that also inhibits OATP1B
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- Current simvastatin dose >20 mg daily
- Measured most recent HbA1c level greater than 7.5% in the last 6 months
- Average glucose by fingerstick or continuous glucose monitor exceeding 180 mg/dL in the last 3 months
- Current uses of any oral or injectable GLP-1 receptor agonists, insulin, or the use of two or more antidiabetic agents
- Currently taking or planning to start other medication known to affect glycemic parameters, such as glucocorticoids, growth hormone, or fluoroquinolones during the study
- Planned to change any prescribed medication during the study
- Planned surgeries or procedures requiring general anesthesia during or within 10 days after completing the study
- Participating in any other interventional study simultaneously
- Dietary restrictions that prevent the consumption of the standardized liquid mixed meal
- Pregnant, nursing, or postpartum in the last 6 months
- Current suicidal ideation or suicide attempt within the past 5 years
- Psychiatric illness, substance use disorder, or eating disorder that, in the opinion of the investigator, would compromise participant safety or study compliance
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Polygenic Assessment and Testing of Heterogeneity and Subtypes in Type 2 Diabetes (PATHS-T2D): A Recall-by-Genotype Study of Physiologic and Pharmacologic Responses
This research study aims to learn about how the body responds to food through different genetic pathways and how these responses may change during a short course of orforglipron. Orforglipron is an oral glucagon-like peptide-1 (GLP-1) receptor agonist that was approved by the U.S. Food and Drug Administration (FDA) on April 1, 2026, for long-term weight management. In longer studies, it has helped people lose weight and improve blood sugar, blood pressure, and cholesterol. By taking part, participants will receive detailed metabolic testing and may receive study results with additional information about their blood sugar and metabolic health.
Read the detailed description
This clinical research study uses a recall-by-genotype strategy to characterize physiologic responses associated with specific genetic pathways and to determine physiological responses and changes under orforglipron challenge.
This study will enroll approximately 100 adults aged 18-79 years who have previously agreed to be recontacted for future studies through the MGB biobank. The target sample size may be adjusted depending on funding availability and to power pharmacologic challenges. The study population will consist of four groups of high genetic risk for glycemic/insulinemic associations based on three pPS, along with controls selected from the interquartile range (IQR) across all pPS to provide a mechanism-agnostic comparator. Blood glucose, insulin, and incretin hormone levels will be measured during a baseline mixed-meal tolerance test (MMTT) at Visit 1. Individuals with diabetes or prediabetes determined through a previous HbA1c ≥ 5.7% or fingerstick glucose levels during the MMTT (fasting glucose of ≥100 mg/dL, 1-hour glucose ≥155 mg/dL, or 2-hour glucose >=140 mg/dL. will be invited to participate in the acute orforglipron challenge and another MMTT at Visit 2.
Participants eligible for the orforglipron challenge will receive orforglipron 2.5mg daily for 13 days at home leading up to Visit 2, another MMTT, during which participants will take the final (14th) dose of orforglipron 2.5mg 30 minutes before starting another MMTT.
- Conditions
- Diabete Type 2, Pharmacogenomic Drug Interaction
- Being tested
- Orforglipron
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OrforglipronDrug
Orforglipron challenge after baseline MMTT
| Study group | Role | What they receive |
|---|---|---|
| Drug challenge | Experimental | MMTT after 12 doses of orforglipron 2.5 mg Receives: Drug: Orforglipron |
| Baseline | No intervention | MMTT pre-drug challenge |
What is being measured
The primary outcome is the main question the study is designed to answer.
Physiologic characterization by MMTT
The primary endpoint will be glucose area under the curve (AUCglc) over the timeframe. For β-cell function, we will assess the first phase of insulin secretion with the insulinogenic index. For insulin resistance, we will calculate HOMA-IR and Matsuda index of insulin sensitivity. We will also capture both phases of insulin secretion by calculating the insulin AUC (AUCins) divided by the AUCglc.
Measured: 1 day
The acute drug challenges
The primary endpoint will be the difference in AUCglc over 180 minutes with drug administration vs. the MMTT without drug administration in Visit 1. We selected this endpoint because the decreased in post-prandial glucose is the most clinically relevant measure of drug response116. Secondary endpoints will include the difference between AUCins/AUCglc, the insulinogenic index (first phase of insulin secretion), and the Matsuda insulin sensitivity.
Measured: 12 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2026
- Study start1 Oct 2026 (estimated)
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabete Type 2Studies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aaron Leong, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07739537
- Sponsor's protocol ID
- 2026P002001
- Other IDs
- 1R01DK148455-01
- Acronym
- PATHS-T2D
- Status last verified
- Jul 2026
- First submitted
- 28 Jul 2026
- Last updated
- 31 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Polygenic Assessment and Testing of Heterogeneity and Subtypes in Type 2 Diabetes (PATHS-T2D): A Recall-by-Genotype Study of Physiologic and Pharmacologic Responses
- ClinicalTrials.gov ID
- NCT07739537
- Acronym / sponsor ID
- PATHS-T2D / 2026P002001
- Conditions
- Diabete Type 2, Pharmacogenomic Drug Interaction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 30 Sep 2029 (estimated)
- Study completion
- 30 Sep 2030 (estimated)
- First posted
- 31 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study aims to learn about how the body responds to food through different genetic pathways and how these responses may change during a short course of orforglipron. Orforglipron is an oral glucagon-like peptide-1 (GLP-1) receptor agonist that was approved by the U.S. Food and Drug Administration (FDA) on April 1, 2026, for long-term weight management. In longer studies, it has helped people lose weight and improve blood sugar, blood pressure, and cholesterol. By taking part, participants will receive detailed metabolic testing and may receive study results with additional information about their blood sugar and metabolic health.
Detailed description
This clinical research study uses a recall-by-genotype strategy to characterize physiologic responses associated with specific genetic pathways and to determine physiological responses and changes under orforglipron challenge.
This study will enroll approximately 100 adults aged 18-79 years who have previously agreed to be recontacted for future studies through the MGB biobank. The target sample size may be adjusted depending on funding availability and to power pharmacologic challenges. The study population will consist of four groups of high genetic risk for glycemic/insulinemic associations based on three pPS, along with controls selected from the interquartile range (IQR) across all pPS to provide a mechanism-agnostic comparator. Blood glucose, insulin, and incretin hormone levels will be measured during a baseline mixed-meal tolerance test (MMTT) at Visit 1. Individuals with diabetes or prediabetes determined through a previous HbA1c ≥ 5.7% or fingerstick glucose levels during the MMTT (fasting glucose of ≥100 mg/dL, 1-hour glucose ≥155 mg/dL, or 2-hour glucose >=140 mg/dL. will be invited to participate in the acute orforglipron challenge and another MMTT at Visit 2.
Participants eligible for the orforglipron challenge will receive orforglipron 2.5mg daily for 13 days at home leading up to Visit 2, another MMTT, during which participants will take the final (14th) dose of orforglipron 2.5mg 30 minutes before starting another MMTT.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Drug challenge | Experimental | Drug: OrforglipronMMTT after 12 doses of orforglipron 2.5 mg |
| Baseline | No intervention | –MMTT pre-drug challenge |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult male or non-pregnant female volunteers (Age 18-79)
- Not currently taking more than two home oral antidiabetic agents, with or without a diagnosis of type 2 diabetes
- Able and willing to stop home oral antidiabetic medications for 5 days prior to the start of the study, with approval from healthcare providers
- Able and willing to give informed consent
Key exclusion criteria (18 listed)
- Known contraindication for orforglipron (e.g., Personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia type 2 (MEN 2), allergies to any component)
- Personal history of pancreatitis, gallbladder disease, intestinal malabsorption, severe gastroparesis, gastric outlet obstruction, or other clinically significant gastrointestinal motility disorder
- History of liver disease or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 x upper limit of normal
- Estimated glomerular filtration rate (eGFR) < 45 mg/min/1.73m2 per the Modification of Diet in Renal Disease equation
- Active gallbladder disease or cholecystectomy within the past 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OrforglipronOrforglipron challenge after baseline MMTT | Drug | Drug challenge |
Primary outcome
Physiologic characterization by MMTT
Time frame: 1 day
The primary endpoint will be glucose area under the curve (AUCglc) over the timeframe. For β-cell function, we will assess the first phase of insulin secretion with the insulinogenic index. For insulin resistance, we will calculate HOMA-IR and Matsuda index of insulin sensitivity. We will also capture both phases of insulin secretion by calculating the insulin AUC (AUCins) divided by the AUCglc.
The acute drug challenges
Time frame: 12 days
The primary endpoint will be the difference in AUCglc over 180 minutes with drug administration vs. the MMTT without drug administration in Visit 1. We selected this endpoint because the decreased in post-prandial glucose is the most clinically relevant measure of drug response116. Secondary endpoints will include the difference between AUCins/AUCglc, the insulinogenic index (first phase of insulin secretion), and the Matsuda insulin sensitivity.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Orforglipron in people with Diabete Type 2 and Pharmacogenomic Drug Interaction, run by Massachusetts General Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nopporn Thangthaeng, PhD, DNP (617-726-8767, pathst2d@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Physiologic characterization by MMTT (time frame: 1 day). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.