Skip to content

Trial · Interventional

Not yet recruitingPhase 4Registry data

PATHS-T2D: A Recall-by-Genotype Study of Physiologic and Pharmacologic Responses

Short name PATHS-T2D

NCTNCT07739537 (opens ClinicalTrials.gov in a new tab)Other id2026P002001Other id1R01DK148455-01
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Not yet recruiting
Phase
Phase 4
Enrollment
100 participants (estimated)
Sponsor
Massachusetts General Hospital · Other
Design
Allocation not applicable · Open label (no masking)
Countries
Not stated
Start
1 Oct 2026 (estimated)
Primary completion
30 Sept 2029 (estimated)
Completion
30 Sept 2030 (estimated)
First posted
31 Jul 2026
Last update posted
31 Aug 2026
Conditions
Diabete Type 2 · Pharmacogenomic Drug Interaction

Timeline

1 trial · 1 not yet recruiting

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
202620272028202920302031
  1. Ph 4

    PATHS-T2D

    NCT07739537

    est. 1 Oct 2026 to est. 30 Sept 2030

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • OrforglipronDrug

Arms2

  • Experimental

    Drug challenge

    MMTT after 12 doses of orforglipron 2.5 mg

  • No intervention

    Baseline

    MMTT pre-drug challenge

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Physiologic characterization by MMTT

    Time frame · 1 day

    Registry description

    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.

  2. The acute drug challenges

    Time frame · 12 days

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 79 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * 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 Exclusion Criteria: * 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 * 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

PepBank is a research reference. Talk to a doctor before you use any peptide.