Friday, January 2, 2026 1/2/2026

Pharmacogenetics of the Response to a GLP1R Agonist

Award Number: R01DK130238
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

Group Awards By:

View Award Description

Pharmacogenetics of the Response to a GLP1R Agonist - Glucagon-like peptide 1 receptor (GLP1R) agonists are an important class of antidiabetic drugs with an attractive clinical profile – including improved glycemic control, weight loss, and decreased risk of major adverse cardiovascular events. While there is substantial variation in the magnitude of individual patients’ responses to these drugs, there are no validated approaches to identify patients most likely to have the largest responses and derive the most clinical benefit. This application proposes a genome-wide association study in the Old Order Amish population to identify genetic variants that predict individuals’ pharmacodynamic responses to GLP1R agonists. Based on preliminary data from the Principal Investigators’ research, the proposed project will measure pharmacodynamic endpoints related to beneficial effects of GLP1R agonists. Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish population in Lancaster County, PA. In order to assess pharmacodynamic responses, research participants will undergo two frequently sampled intravenous glucose tolerance tests (FSIGT). The first FSIGT will be conducted at baseline prior to administration of drug. The second FSIGT will be conducted after six weeks of treatment with semaglutide (0.25 mg/wk X 4 wks; 0.5 mg/sk X 2 wks). The proposal proposes two specific aims: • Specific Aim #1. To identify genetic variants associated with effects of a GLP1R agonist to enhance glucose- stimulated first phase insulin secretion in the two FSIGTs (before and after administration of drug). • Specific Aim #2. To identify genetic variants associated with the effect of a GLP1R agonist to accelerate the rate of glucose disappearance as assessed in the two FSIGTs (before and after administration of drug). Genotyping will be conducted using a high-density array with comprehensive coverage of DNA sequence variants. The project will leverage a global imputation panel generated from whole genome sequence data on ~ 100K subjects including 1,025 Amish individuals obtained through the NHLBI-sponsored Trans-Omics for Precision Medicine (TOPMed) program. Previous genetic studies conducted in the Old Order Amish population have been highly predictive of observations in the general population and relevant patient populations. Based on these precedents, we anticipate that genetic variants in this study are very likely to be predictive of clinical responses of GLP1R agonist-treated type 2 diabetic patients. The proposed study is a step toward the long- term objective of identifying genetic biomarkers to predict an individual patient’s response to GLP1R agonists. Availability of predictive biomarkers would enable physicians to prescribe optimal therapies for each individual patient based on predictors of beneficial response. This type of Precision Medicine approach, based on predictive pharmacogenomic biomarkers, would be a transformational advance in the way diabetes drugs are prescribed.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $672,063 )
2026	2026	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	12/4/2025	NON-COMPETING CONTINUATION	$672,063
														Subtotal = $672,063

Issue Date FY: 2025 ( Subtotal = $604,825 )
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/25/2024	NON-COMPETING CONTINUATION	$604,825
														Subtotal = $604,825

Issue Date FY: 2024 ( Subtotal = $645,147 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	3/21/2024	NON-COMPETING CONTINUATION	$0
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	5/7/2024	NON-COMPETING CONTINUATION	$40,322
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/10/2024	NON-COMPETING CONTINUATION	$604,825
														Subtotal = $645,147

Issue Date FY: 2023 ( Subtotal = $672,029 )
2023	2023	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	1/5/2023	NON-COMPETING CONTINUATION	$67,204
2023	2023	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	12/15/2022	NON-COMPETING CONTINUATION	$0
2023	2023	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/30/2022	NON-COMPETING CONTINUATION	$604,825
														Subtotal = $672,029

Issue Date FY: 2022 ( Subtotal = $672,029 )
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/18/2021	NEW	$672,029
														Subtotal = $672,029

Grand Total All Awards = $3,266,093

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Pharmacogenetics of the Response to a GLP1R Agonist

Award Number: R01DK130238

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer