Trial reportDiabetes care2024
Longitudinal Effects of Glucose-Lowering Medications on β-Cell Responses and Insulin Sensitivity in Type 2 Diabetes: The GRADE Randomized Clinical Trial.
Trial report in Diabetes care, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01794143. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study
Who cites it
17 citing papers in PubMed, 15 citations in OpenAlex.
- Comparison of the Continuous Glucose Monitoring Profiles of Four Glucose-Lowering Medications in the GRADE Randomized Trial.Diabetes care · 2026Trial
- Trial
- Differential Treatment Effects on β-Cell Function Using Model-Based Parameters in Type 2 Diabetes: Results From the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Diabetes care · 2025 · on this mapTrial
- Trial
- Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial.Diabetes care · 2024 · on this mapTrial
- Time in range during caloric restriction in type 2 diabetes with obesity.Journal of diabetes investigation · 2026Article
- Association Between Insulin Regimen and Cardiovascular Risk in Indonesian Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study.Therapeutics and clinical risk management · 2026Article
- The Role of Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Cardiovascular-Kidney-Metabolic Syndrome.JACC. Advances · 2026Article
- Defining Severe Diabetes Mellitus: A Consensus Framework for Grading and Staging Diabetes Based on Pathophysiology and Complications.Diabetes & metabolism journal · 2025Review
- Antidiabetic agents and male fertility: unraveling the impact of glucose-lowering therapies on sperm quality in diabetic males-a narrative review.Translational andrology and urology · 2025Review
- Simultaneous Evaluation of Shear Wave Elastography and C-Peptide Index for Predicting Need of Insulin Therapy in Type 2 Diabetes: A Pilot Study.Journal of personalized medicine · 2025Article
- The Modern Role of Basal Insulin in Advancing Therapy in People With Type 2 Diabetes.Diabetes care · 2025Review
- Consensus on the key characteristics of metabolism disruptors.Nature reviews. Endocrinology · 2025Review
- Current Status of Glucagon-like Peptide-1 Receptor Agonists in Metabolic Dysfunction-associated Steatotic Liver Disease: A Clinical Perspective.Journal of clinical and translational hepatology · 2025Review
- Long-Term Efficacy Trajectories of GLP-1 Receptor Agonists: A Systematic Review and Network Meta-Analysis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Associations of physiologic subtypes based on HOMA2 indices of β-cell function and insulin sensitivity with the risk of kidney function decline, cardiovascular disease, and all-cause mortality from the 4C study.Cardiovascular diabetology · 2024Article
- Ketoacidosis and SGLT2 Inhibitors: A Narrative Review.Metabolites · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 10 institutions in 1 country.
Funding
Abstract
objectiveTo 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
methodsIn 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.
resultsHOMA2-%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.
conclusionsThe 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.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.