Longitudinal Effects of Glucose-Lowering Medications on β-Cell Responses and Insulin Sensitivity in Type 2 Diabetes: The GRADE Randomized Clinical Trial.

Rasouli N, Younes N, Ghosh A, Albu J, Cohen RM, DeFronzo RA, Diaz E, Sayyed Kassem L, Luchsinger JA, McGill JB, Sivitz WI, Tamborlane WV, Utzschneider KM, Kahn SE

Diabetes care1 Apr 2024Cited by 20 (Europe PMC)

PMID38211595PMCIDPMC10973918DOI10.2337/dc23-1070PepBankPUB-38211595

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study5

4 results from studies that gave the peptide. 4 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on metformin, insulin sensitivity (HOMA2-%S) did not change from baseline with liraglutide.
In plain wordsIn adults with type 2 diabetes on metformin, liraglutide did not change insulin sensitivity from baseline.
Peptide
Liraglutide
Outcome
No significant changeHOMA2-%S change from baseline
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
while it did not change from baseline in the other treatment groups.
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
Report a problemFND-3821159501
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on metformin, the C-peptide index at year 5 was higher with liraglutide than with glargine or glimepiride (P < 0.001).
In plain wordsIn adults with type 2 diabetes on metformin, liraglutide kept a higher C-peptide index at year 5 than glargine or glimepiride.
Peptide
Liraglutide
Outcome
IncreaseC-peptide index at year 5, liraglutide versus glargine and glimepiride
Study
n: not reported in source
Comparator
Glargine and glimepiride
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Measurements
C-peptide index
0.8 (nmol/L)/(mg/dL) * 100
liraglutide, year 5
Source sentences
Summary
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],
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
Report a problemFND-3821159503
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on metformin, the C-peptide index at year 5 was similar between liraglutide and sitagliptin.
In plain wordsIn adults with type 2 diabetes on metformin, the C-peptide index at year 5 was similar with liraglutide and sitagliptin.
Peptide
Liraglutide
Outcome
No significant changeC-peptide index at year 5, liraglutide versus sitagliptin
Study
n: not reported in source
Comparator
Sitagliptin
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Measurements
C-peptide index
0.8 (nmol/L)/(mg/dL) * 100
liraglutide, year 5
Source sentences
Summary
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],
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
Report a problemFND-3821159504
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on metformin, the total C-peptide response at year 5 was greatest with liraglutide (1.54), followed by sitagliptin, glargine and glimepiride (P < 0.001).
In plain wordsIn adults with type 2 diabetes on metformin, liraglutide had the greatest total C-peptide response at year 5 of the four drugs.
Peptide
Liraglutide
Outcome
IncreaseTotal C-peptide response at year 5
Study
n: not reported in source
Comparator
Sitagliptin, glargine and glimepiride
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Measurements
Total C-peptide response
1.54 (nmol/L)/(mg/dL) * 100
liraglutide, year 5
Source sentences
Summary
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].
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
Report a problemFND-3821159505

Studies that did not test the peptide alone1

In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Liraglutide.

05HumanNot a test of Liraglutide aloneRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes on metformin, HOMA2-%B and C-peptide responses rose at year 1 in all groups, including liraglutide, then declined progressively.
In plain wordsIn adults with type 2 diabetes on metformin, beta-cell measures rose at year 1 in all four groups and then declined over time.
Peptide
Liraglutide
Outcome
MixedHOMA2-%B and C-peptide responses over time (all groups)
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
HOMA2-%B and C-peptide responses were increased to variable degrees at year 1 in all groups but then declined progressively over time.
2 context sentences(design, population, supporting numbers)
Summary · context
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.
Summary · context
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.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Report a problemFND-3821159502

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT01794143

A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes

GRADE Study Groupn = 7,850May 2013 to 30 Apr 2021

Type 2 Diabetes · Comparative Effectiveness of Glycemia-lowering Medications

Trial page ClinicalTrials.govUpdated 10 Feb 2026

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 11:11 UTC
Study results updated
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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