Language
English
Publication Date
4-1-2024
Journal
Diabetes Care
DOI
10.2337/dc23-1059
PMID
38190619
PMCID
PMC10973903
PubMedCentral® Posted Date
1-8-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Objective: To compare the effects of insulin sensitivity and β-cell function over time on HbA1c and durability of glycemic control in response to dual therapy.
Research design and methods: GRADE participants were randomized to glimepiride (n = 1,254), liraglutide (n = 1,262), or sitagliptin (n = 1,268) added to baseline metformin and followed for mean ± SD 5.0 ± 1.3 years, with HbA1c assessed quarterly and oral glucose tolerance tests at baseline, 1, 3, and 5 years. We related time-varying insulin sensitivity (HOMA 2 of insulin sensitivity [HOMA2-%S]) and early (0-30 min) and total (0-120 min) C-peptide (CP) responses to changes in HbA1c and glycemic failure (primary outcome HbA1c ≥7% [53 mmol/mol] and secondary outcome HbA1c >7.5% [58 mmol/mol]) and examined differential treatment responses.
Results: Higher HOMA2-%S was associated with greater initial HbA1c lowering (3 months) but not subsequent HbA1c rise. Greater CP responses were associated with a greater initial treatment response and slower subsequent HbA1c rise. Higher HOMA2-%S and CP responses were each associated with lower risk of primary and secondary outcomes. These associations differed by treatment. In the sitagliptin group, HOMA2-%S and CP responses had greater impact on initial HbA1c reduction (test of heterogeneity, P = 0.009 HOMA2-%S, P = 0.018 early CP, P = 0.001 total CP) and risk of primary outcome (P = 0.005 HOMA2-%S, P = 0.11 early CP, P = 0.025 total CP) but lesser impact on HbA1c rise (P = 0.175 HOMA2-%S, P = 0.006 early CP, P < 0.001 total CP) in comparisons with the glimepiride and liraglutide groups. There were no differential treatment effects on secondary outcome.
Conclusions: Insulin sensitivity and β-cell function affected treatment outcomes irrespective of drug assignment, with greater impact in the sitagliptin group on initial (short-term) HbA1c response in comparison with the glimepiride and liraglutide groups.
Keywords
Humans, Hypoglycemic Agents, Diabetes Mellitus, Type 2, Insulin Resistance, Liraglutide, Glycated Hemoglobin, Metformin, Sitagliptin Phosphate, Treatment Outcome, Blood Glucose, Drug Therapy, Combination, Sulfonylurea Compounds
Published Open-Access
yes
Recommended Citation
Utzschneider, Kristina M; Younes, Naji; Butera, Nicole M; et al., "Impact of Insulin Sensitivity and β-Cell Function Over Time on Glycemic Outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE): Differential Treatment Effects of Dual Therapy" (2024). Faculty and Staff Publications. 4339.
https://digitalcommons.library.tmc.edu/baylor_docs/4339