TY - JOUR
T1 - Longitudinal Effects of Glucose-Lowering Medications on β-Cell Responses and Insulin Sensitivity in Type 2 Diabetes
T2 - The GRADE Randomized Clinical Trial
AU - GRADE Research Group
AU - Rasouli, Neda
AU - Younes, Naji
AU - Ghosh, Alokananda
AU - Albu, Jeanine
AU - Cohen, Robert M.
AU - Defronzo, Ralph A.
AU - Diaz, Elsa
AU - Kassem, Laure Sayyed
AU - Luchsinger, Josée A.
AU - McGill, Janet B.
AU - Sivitz, William I.
AU - Tamborlane, William V.
AU - Utzschneider, Kristina M.
AU - Kahn, Steven E.
N1 - Publisher Copyright:
© 2024 by the American Diabetes Association.
PY - 2024/4
Y1 - 2024/4
N2 - OBJECTIVE To compare the long-term effects of glucose-lowering medications (insulin glargine U-100, glimepiride, liraglutide, and sitagliptin) when added to metformin on insulin sensitivity and β-cell function. RESEARCH DESIGN AND METHODS In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) cohort with type 2 diabetes (n = 4,801), HOMA2 was used to estimate insulin sensitivity (HOMA2-%S) and fasting β-cell function (HOMA2-%B) at baseline and 1, 3, and 5 years on treatment. Oral glucose tolerance test β-cell responses (C-peptide index [CPI] and total C-peptide response [incremental C-peptide/ incremental glucose over 120 min]) were evaluated at the same time points. These responses adjusted for HOMA2-%S in regression analysis provided estimates of β-cell function. RESULTS HOMA2-%S increased from baseline to year 1 with glargine and remained stable thereafter, while it did not change from baseline in the other treatment groups. HOMA2-%B and C-peptide responses were increased to variable degrees at year 1 in all groups but then declined progressively over time. At year 5, CPI was similar between liraglutide and sitagliptin, and higher for both than for glargine and glimepiride [0.80, 0.87, 0.74, and 0.64 (nmol/L)/(mg/dL) * 100, respectively; P < 0.001], while the total C-peptide response was greatest with liraglutide, followed in descending order by sitagliptin, glargine, and glimepiride [1.54, 1.25, 1.02, and 0.87 (nmol/L)/(mg/dL) * 100, respectively, P < 0.001]. After adjustment for HOMA2-%S to obtain an estimate of β-cell function, the nature of the change in β-cell responses reflected those in β-cell function. CONCLUSIONS The differential long-term effects on insulin sensitivity and β-cell function of four different glucose-lowering medications when added to metformin highlight the importance of the loss of β-cell function in the progression of type 2 diabetes.
AB - OBJECTIVE To compare the long-term effects of glucose-lowering medications (insulin glargine U-100, glimepiride, liraglutide, and sitagliptin) when added to metformin on insulin sensitivity and β-cell function. RESEARCH DESIGN AND METHODS In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) cohort with type 2 diabetes (n = 4,801), HOMA2 was used to estimate insulin sensitivity (HOMA2-%S) and fasting β-cell function (HOMA2-%B) at baseline and 1, 3, and 5 years on treatment. Oral glucose tolerance test β-cell responses (C-peptide index [CPI] and total C-peptide response [incremental C-peptide/ incremental glucose over 120 min]) were evaluated at the same time points. These responses adjusted for HOMA2-%S in regression analysis provided estimates of β-cell function. RESULTS HOMA2-%S increased from baseline to year 1 with glargine and remained stable thereafter, while it did not change from baseline in the other treatment groups. HOMA2-%B and C-peptide responses were increased to variable degrees at year 1 in all groups but then declined progressively over time. At year 5, CPI was similar between liraglutide and sitagliptin, and higher for both than for glargine and glimepiride [0.80, 0.87, 0.74, and 0.64 (nmol/L)/(mg/dL) * 100, respectively; P < 0.001], while the total C-peptide response was greatest with liraglutide, followed in descending order by sitagliptin, glargine, and glimepiride [1.54, 1.25, 1.02, and 0.87 (nmol/L)/(mg/dL) * 100, respectively, P < 0.001]. After adjustment for HOMA2-%S to obtain an estimate of β-cell function, the nature of the change in β-cell responses reflected those in β-cell function. CONCLUSIONS The differential long-term effects on insulin sensitivity and β-cell function of four different glucose-lowering medications when added to metformin highlight the importance of the loss of β-cell function in the progression of type 2 diabetes.
UR - http://www.scopus.com/inward/record.url?scp=85188903190&partnerID=8YFLogxK
U2 - 10.2337/dc23-1070
DO - 10.2337/dc23-1070
M3 - Article
C2 - 38211595
AN - SCOPUS:85188903190
SN - 0149-5992
VL - 47
SP - 580
EP - 588
JO - Diabetes care
JF - Diabetes care
IS - 4
ER -