LivingGLP1
Study S000873

Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study

Included trial: extracted dataClinicalTrials.gov recordStudy Protocol (PDF)Statistical Analysis Plan: Manuscript - Microvascular and Cardiovascular Outcomes (OP2) (PDF)Statistical Analysis Plan: GRADE Study (PDF)Statistical Analysis Plan: Manuscript - Long Term Differences in Metabolic Status (OP1) (PDF)Informed Consent Form (PDF)

Registration

Registration
NCT01794143
Acronym
GRADE
Study type
INTERVENTIONAL
Allocation
RANDOMIZED
Phase
PHASE3
Masking
NONE
Status
COMPLETED
Enrollment
7850
Start
2013-05
Primary completion
2021-04-30
Lead sponsor
GRADE Study Group
Conditions
Type 2 Diabetes; Comparative Effectiveness of Glycemia-lowering Medications
Interventions
DRUG:Sulfonylurea (glimepiride); DRUG:DPP-4 inhibitor (sitagliptin); DRUG:GLP-1 receptor agonist (liraglutide); DRUG:Insulin (glargine)
Results posted
TRUE
Secondary identifiers
NIH:1U01DK098246-01

Registered primary outcomes

  • Time to HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication [Quarterly for 4 to 7 years]
  • HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication [Quarterly, 4-7 years]

Linked records (23)

Automatic links, confirmed or rejected during screening. A record citing this registration may be a secondary analysis, a commentary or a review that mentions the trial.
RecordTitleYearDesignIdentifiersLink basis
R0008020Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes: The GRADE Randomized Clinical Trial.
Luchsinger JA, JAMA internal medicine
2025Randomized trialPMID 40388190DOIcites ClinicalTrials.gov:NCT01794143; registry reference RESULT:40388190
R0010237Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes.
Natale P, The Cochrane database of systematic reviews
2025Systematic reviewPMID 39963952DOIcites ClinicalTrials.gov:NCT01794143; registry reference DERIVED:39963952
R0017051Differences in Prevalence and Incidence of Electrocardiogram Abnormalities and Cardiovascular Autonomic Neuropathy Among Randomized Glucose-Lowering Treatments in Early Type 2 Diabetes: The Glycemia Reduction Approaches in Diabetes (GRADE) Cohort.
Pop-Busui R, Diabetes care
2025Randomized trialPMID 40986645DOIregistry reference RESULT:40986645
R0018491Association of Hospitalizations With Randomized Glycemia-Lowering Treatment in GRADE.
Hsia DS, Diabetes care
2025Randomized trialPMID 40424051DOIregistry reference RESULT:40424051
R0019659Weight Gain Was Associated With Worsening Glycemia and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes Independent of Diabetes Medication in the GRADE Randomized Controlled Trial.
Wexler DJ, Diabetes care
2025Randomized trialPMID 40267365DOIregistry reference RESULT:40267365
R0021569Common genetic variants near SLC2A2 and glycemic response to glimepiride in the GRADE comparative effectiveness clinical trial.
Li JH, medRxiv : the preprint server for health sciences
2025Other trialPMID 41282760DOIcites ClinicalTrials.gov:NCT01794143; registry reference DERIVED:41282760
R0021775Differential 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).
Utzschneider KM, Diabetes care
2025Randomized trialPMID 39998948DOIregistry reference RESULT:39998948
R0007788Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).
Gonzalez JS, Diabetes care
2024Randomized trialPMID 38416773DOIregistry reference RESULT:38416773
R0020516Impact of Glucose-Lowering Medications on Health-Related Quality of Life in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).
Cherrington AL, Diabetes care
2024Randomized trialPMID 38190625DOIregistry reference RESULT:38190625
R0020895Glycemia reduction in type 2 diabetes-Hypoglycemia outcomes: A randomized clinical trial.
Seaquist ER, PloS one
2024Randomized trialPMID 39546502DOIcites ClinicalTrials.gov:NCT01794143; registry reference RESULT:39546502
R0021754Cardiovascular Outcomes in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study).
Green JB, Circulation
2024Randomized trialPMID 38344820DOIcites ClinicalTrials.gov:NCT01794143; registry reference RESULT:38344820
R0022156Comparative Effects of Randomized Second-line Therapy for Type 2 Diabetes on a Composite Outcome Incorporating Glycemic Control, Body Weight, and Hypoglycemia: An Analysis of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).
Kirkman MS, Diabetes care
2024Randomized trialPMID 38194519DOIregistry reference RESULT:38194519
R0022160Longitudinal Effects of Glucose-Lowering Medications on β-Cell Responses and Insulin Sensitivity in Type 2 Diabetes: The GRADE Randomized Clinical Trial.
Rasouli N, Diabetes care
2024Randomized trialPMID 38211595DOIregistry reference RESULT:38211595
R0022309Impact 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.
Utzschneider KM, Diabetes care
2024Randomized trialPMID 38190619DOIregistry reference RESULT:38190619
R0022624The incidence of retinopathy in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness study (GRADE).
Hsia DS, Journal of diabetes and its complications
2024OtherPMID 38354481DOIcites ClinicalTrials.gov:NCT01794143; registry reference RESULT:38354481
R0023016Association of Baseline Factors With Glycemic Outcomes in GRADE: A Comparative Effectiveness Randomized Clinical Trial.
Garvey WT, Diabetes care
2024Randomized trialPMID 38285957DOIregistry reference RESULT:38285957
R0023025The Use of Rescue Insulin in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).
Hollander PA, Diabetes care
2024Randomized trialPMID 37756542DOIregistry reference RESULT:37756542
R0024626Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes: The GRADE Randomized Clinical Trial.
Wexler DJ, JAMA internal medicine
2023Randomized trialPMID 37213109DOIcites ClinicalTrials.gov:NCT01794143; registry reference RESULT:37213109
R0010626Glycemia Reduction in Type 2 Diabetes - Glycemic Outcomes.
GRADE Study Research Group, The New England journal of medicine
2022Randomized trialPMID 36129996DOIcites ClinicalTrials.gov:NCT01794143; registry reference RESULT:36129996
R0024560Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes.
GRADE Study Research Group, The New England journal of medicine
2022Randomized trialPMID 36129997DOIcites ClinicalTrials.gov:NCT01794143; registry reference RESULT:36129997
R0028529Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight.
Sivitz WI, Diabetes care
2020Nonrandomized studyPMID 32139384DOIcites ClinicalTrials.gov:NCT01794143; registry reference RESULT:32139384
R0027789Baseline Characteristics of Randomized Participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).
Wexler DJ, Diabetes care
2019Randomized trialPMID 31391203DOIcites ClinicalTrials.gov:NCT01794143; registry reference RESULT:31391203
R0019619Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE).
Nathan DM, Diabetes care
2013ProtocolPMID 23690531DOIregistry reference RESULT:23690531