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

ConditionsDiabete Type 2 Pharmacogenomic Drug Interaction

Trial statusNot yet recruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age18-79

SponsorMassachusetts General Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

Orforglipron
Drug
Orforglipron challenge after baseline MMTT

Treatment groups

100 Participants

are divided into 2 treatment groups

Group A: Drug challengeExperimental treatment 1 intervention

Group B: BaselineNo intervention 0 interventions

Trial outcomes

Primary outcomes

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.

Time frame

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.

Time frame

12 days

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Massachusetts General Hospital

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: