RT Journal Article
T1 The study to understand the genetics of the acute response to metformin and glipizide in humans (SUGAR-MGH): design of a pharmacogenetic resource for type 2 diabetes.
A1 Walford, Geoffrey A
A1 Colomo, Natalia
A1 Todd, Jennifer N
A1 Billings, Liana K
A1 Fernandez, Marlene
A1 Chamarthi, Bindu
A1 Warner, A Sofia
A1 Davis, Jaclyn
A1 Littleton, Katherine R
A1 Hernandez, Alicia M
A1 Fanelli, Rebecca R
A1 Lanier, Amelia
A1 Barbato, Corinne
A1 Ackerman, Rachel J
A1 Khan, Sabina Q
A1 Bui, Rosa
A1 Garber, Laurel
A1 Stolerman, Elliot S
A1 Moore, Allan F
A1 Huang, Chunmei
A1 Kaur, Varinderpal
A1 Harden, Maegan
A1 Taylor, Andrew
A1 Chen, Ling
A1 Manning, Alisa K
A1 Huang, Paul
A1 Wexler, Deborah
A1 McCarthy, Rita M
A1 Lo, Janet
A1 Thomas, Melissa K
A1 Grant, Richard W
A1 Goldfine, Allison
A1 Hudson, Margo S
A1 Florez, Jose C
K1 Alelos
K1 Glucosa sanguínea
K1 Diabetes Mellitus, Tipo II
K1 Predisposición genética a la enfermedad
K1 glipicida
K1 Prueba de tolerancia a la glucosa
K1 Insulina
K1 Biomarcadores
K1 Hipoglicemiantes
K1 Fenotipo
K1 Polimorfismo de nucleótido único
K1 Proteína 2 similar al factor de transcripción 7
K1 Resultado del tratamiento
AB OBJECTIVEGenome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046) is a novel resource of genetic and biochemical data following glipizide and metformin administration. We describe recruitment, enrollment, and phenotyping procedures and preliminary results for the first 668 of our planned 1,000 participants enriched for individuals at risk of requiring anti-diabetic therapy in the future.METHODSAll individuals are challenged with 5 mg glipizide × 1; twice daily 500 mg metformin × 2 days; and 75-g oral glucose tolerance test following metformin. Genetic variants associated with glycemic traits and blood glucose, insulin, and other hormones at baseline and following each intervention are measured.RESULTSApproximately 50% of the cohort is female and 30% belong to an ethnic minority group. Following glipizide administration, peak insulin occurred at 60 minutes and trough glucose at 120 minutes. Thirty percent of participants experienced non-severe symptomatic hypoglycemia and required rescue with oral glucose. Following metformin administration, fasting glucose and insulin were reduced. Common genetic variants were associated with fasting glucose levels.CONCLUSIONSSUGAR-MGH represents a viable pharmacogenetic resource which, when completed, will serve to characterize genetic influences on pharmacological perturbations, and help establish the functional relevance of newly discovered genetic loci to therapy of type 2 diabetes.TRIAL REGISTRATIONClinicalTrials.gov NCT01762046.
PB Public Library of Science
YR 2015
FD 2015-03-26
LK http://hdl.handle.net/10668/2332
UL http://hdl.handle.net/10668/2332
LA en
NO Walford GA, Colomo N, Todd JN, Billings LK, Fernandez M, Chamarthi B, et al. The study to understand the genetics of the acute response to metformin and glipizide in humans (SUGAR-MGH): design of a pharmacogenetic resource for type 2 diabetes. PLoS ONE. 2015; 10(3):e0121553
NO ClinicalTrials.gov NCT01762046; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 6, 2025