Differential Longitudinal Effects of Glucose-Lowering Medications on Glucagon and C-peptide Responses in the Glycemia Reduction Approaches in Diabetes: a Comparative Effectiveness Study (GRADE).

Details

• Alternative Title:
  Diabetes Care, 2025, v. 49, no. 2: Differential Longitudinal Effects of Glucose-Lowering Medications on Glucagon and C-peptide Responses in the Glycemia Reduction Approaches in Diabetes: a Comparative Effectiveness Study (GRADE).
• Journal Article:
  Diabetes Care
• Personal Author:
  Kahn, Steven E. ; Tripputi, Mark ; Lachin, John M. ; Balasubramanyam, Ashok ; Banerji, Mary Ann ; Barzilay, Joshua ; Cohen, Robert M. ; Garvey, W. Timothy ; Gramzinski, Michaela R. ; Rasouli, Neda ; Rhee, Mary ; Seegmiller, Jesse C. ; Singh, Vatsala ; Sivitz, William I. ; Steffes, Michael W. ; Utzschneider, Kristina ; DeFronzo, Ralph A.
• Corporate Authors:
  for the GRADE Research Group
• Description:
  To determine the longitudinal effects on α-cell function of four classes of glucose-lowering agents added to metformin in adults with type 2 diabetes.
  
  In a multicenter, randomized study, 5,047 participants ≥30 years of age with type 2 diabetes taking 1,000-2,000 mg metformin daily, HbA1c 6.8%-8.5%, were randomized to receive insulin glargine U100, glimepiride, liraglutide, or sitagliptin. In a subset of 724 participants, baseline and longitudinal measures of α-cell function were assessed as the fasting glucagon concentration and change in glucagon from fasting to 30 min following oral glucose (glucagon index GGI). Whether these measures and those of β-cell function (fasting C-peptide and C-peptide index CPI) were related to the primary metabolic outcome (HbA1c ≥7.0%) was examined.
  
  Baseline fasting glucagon and GGI were not associated with the primary metabolic outcome (2 df; P = 0.55), whereas the β-cell measures were (2 df; P = 0.04). Treatment-associated changes in fasting glucagon, GGI, and fasting C-peptide were not associated with the primary metabolic outcome, while changes in CPI were, in models unadjusted (P < 0.05) or adjusted (P < 0.001) for α-cell function. A 1-SD increase in CPI was associated with a 17% reduction in the risk of the primary metabolic outcome. There were no clear differential effects of the medications on glucagon responses.
  
  There were different patterns of effects of the four glucose-lowering medications on the α-cell, with no relationship of α-cell function with worsening glycemia. Thus, in treating type 2 diabetes, for choice of medication(s) the focus should primarily be on their impact on β-cell function.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Glucagon
  • C-Peptide
  • Diabetes Mellitus, Type 2
  • Middle Aged
  • Male
  • Female
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Metformin
  More +
• Keywords:
  • α-cell
  • β-cell
  • oral glucose
  • C-peptide
  • glucagon
  • DPP-4 inhibitor
  • sitagliptin
  • basal insulin
  • insulin glargine
  • GLP-1 receptor agonist
  More +
• Source:
  Diabetes Care, 2025, v. 49, no. 2
• DOI:
  https://doi.org/10.2337/dc25-2186
• ISSN:
  0149-5992 ; 1935-5548
• Pubmed ID:
  41432725
• Pubmed Central ID:
  PMC12824799
• Document Type:
  Text
• Funding:
  UL1 TR000445/TR/NCATS NIH HHSUnited States/ ; HL/NHLBI NIH HHSUnited States/ ; UL1 TR002529/TR/NCATS NIH HHSUnited States/ ; U01DK098246/Division of Diabetes, Endocrinology, and Metabolic Diseases/ ; UM1 TR004406/TR/NCATS NIH HHSUnited States/ ; R01 DK123330/DK/NIDDK NIH HHSUnited States/ ; UL1 TR000439/TR/NCATS NIH HHSUnited States/ ; P30 DK020541/DK/NIDDK NIH HHSUnited States/ ; U34DK088043/Division of Diabetes, Endocrinology, and Metabolic Diseases/ ; P30 DK020572/DK/NIDDK NIH HHSUnited States/ ; UL1 TR002345/TR/NCATS NIH HHSUnited States/ ; UL1 TR002548/TR/NCATS NIH HHSUnited States/ ; U34 DK088043/DK/NIDDK NIH HHSUnited States/ ; R01 DK104845/DK/NIDDK NIH HHSUnited States/ ; UL1 TR002537/TR/NCATS NIH HHSUnited States/ ; P30 DK092926/DK/NIDDK NIH HHSUnited States/ ; American Diabetes Association/ ; UL1 TR002535/TR/NCATS NIH HHSUnited States/ ; P30 DK072476/DK/NIDDK NIH HHSUnited States/ ; P30 DK079626/DK/NIDDK NIH HHSUnited States/ ; UL1 TR001409/TR/NCATS NIH HHSUnited States/ ; U01 DK098246/DK/NIDDK NIH HHSUnited States/ ; UL1 TR001449/TR/NCATS NIH HHSUnited States/ ; UL1 TR002489/TR/NCATS NIH HHSUnited States/ ; U54 GM104940/GM/NIGMS NIH HHSUnited States/ ; UL1 TR001108/TR/NCATS NIH HHSUnited States/ ; UL1 TR002378/TR/NCATS NIH HHSUnited States/ ; P30 DK035816/DK/NIDDK NIH HHSUnited States/ ; UL1 TR001425/TR/NCATS NIH HHSUnited States/ ; UM1 TR004528/TR/NCATS NIH HHSUnited States/ ; R01 DK109956/DK/NIDDK NIH HHSUnited States/ ; UL1 TR002243/TR/NCATS NIH HHSUnited States/ ; P30 DK017047/DK/NIDDK NIH HHSUnited States/ ; CC/CDC HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  325-334 (19 pdf pages)
• Volume:
  49
• Issue:
  2
• Download URL:
  https://stacks.cdc.gov/view/cdc/260883/cdc_260883_DS1.pdf
• File Type:
  [PDF - 975.21 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:89f4e38eef6442a60e7dd7257f86beead753f550de57ab0a1725cda6e0266bba3738a07dc76f25a6cd2b60b2114ba800d5439c1d338b4c68210430a1610a2389