Weight 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, Garvey WT, Ghosh A, Kazemi EJ, Krause-Steinrauf H, Ahmann AJ, Brown-Friday J, Casula S, Cherrington AL, Elasy TA, Fortmann SP, Krakoff JA, Mudaliar S, Tiktin M, Younes N

Diabetes care1 Jun 2025Cited by 7 (Europe PMC)

PMID40267365PMCIDPMC12094209DOI10.2337/dc24-2825PepBankPUB-40267365

Source link PubMedAsk about this study

Jump to 9 results

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 study9

2 results from studies that gave the peptide. 2 results from people.

01HumanRandomized controlled trialEfficacy outcome
In metformin-treated T2D participants, first-year liraglutide-arm mean weight change was -3.5 kg (95% CI -3.8 to -3.2); P<0.0001 was reported for the treatment-group changes, not an isolated liraglutide within-arm test.
In plain wordsIn T2D participants taking metformin, liraglutide was linked to 3.5 kg first-year weight loss compared with initial weight.
Peptide
Liraglutide
Outcome
DecreaseWeight change during first year
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 1 yearAs given in this study (human).
Measurements
Liraglutide mean weight change
−3.5 kg
first year
95% CI
−3.8 to −3.2 kg
liraglutide first-year mean change
Reported treatment-group P-value
< 0.0001
reported with all four arm changes; no isolated within-arm P inferred
Source sentences
Summary
Mean (95% CI) weight change (kg) during the first year was -3.5 (-3.8,-3.2) with liraglutide,-1.07 (-1.4,-0.78) with sitagliptin, 0.45 (0.16, 0.74) with glargine, and 0.89 (0.60, 1.2) with glimepiride (P < 0.0001).
2 context sentences(design, population, supporting numbers)
Summary · context
The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.
Summary · context
We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.
Report a problemFND-4026736501
02HumanRandomized controlled trialEfficacy outcome
In metformin-treated T2D participants, weight decreased after the first year in every randomized treatment group, including liraglutide; no native later-period coefficient or analyzed N was reported.
In plain wordsIn T2D participants taking metformin, weight decreased after the first year in all groups, including liraglutide; no native estimate was reported.
Peptide
Liraglutide
Outcome
DecreaseWeight change after first year
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Thereafter, weight decreased in all groups.
2 context sentences(design, population, supporting numbers)
Summary · context
The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.
Summary · context
We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.
Report a problemFND-4026736502

Studies that did not test the peptide alone7

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.

03HumanNot a test of Liraglutide aloneObservational studyOther
In pooled metformin-treated GRADE T2D cohorts including liraglutide, weight gain within the first 6 months was associated with increased HbA1c-above 7.5% risk, with modest treatment differences and no reported coefficient; no native-drug effect or exact weight reference was stated.
In plain wordsIn pooled T2D cohorts including liraglutide, first 6-month weight gain was linked to higher risk of HbA1c above 7.5%; no association coefficient was reported.
Peptide
Liraglutide
Outcome
IncreaseHbA1c above7.5% associated with first6-month weight gain
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Weight gain within the first 6 months was associated with increased risk of HbA1c >7.5%, with modest differences by treatment, and with subsequent CVD (HR 1.03 [95% CI 1.005, 1.06]).
2 context sentences(design, population, supporting numbers)
Summary · context
The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.
Summary · context
We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.
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-4026736503
04HumanNot a test of Liraglutide aloneObservational studyOther
In pooled metformin-treated GRADE T2D cohorts including liraglutide, first 6-month weight gain was associated with subsequent CVD (HR 1.03,95% CI 1.005 to 1.06 per kilogram of weight change); no native-drug effect or exact weight reference was stated.
In plain wordsIn pooled T2D cohorts including liraglutide, first 6-month weight gain was linked to higher later cardiovascular-disease risk.
Peptide
Liraglutide
Outcome
IncreaseCardiovascular disease associated with first6-month weight gain
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Hazard ratio
1.03
CVD per kilogram of weight change
95% CI
1.005 to 1.06
CVD HR
Source sentences
Summary
Weight gain within the first 6 months was associated with increased risk of HbA1c >7.5%, with modest differences by treatment, and with subsequent CVD (HR 1.03 [95% CI 1.005, 1.06]).
2 context sentences(design, population, supporting numbers)
Summary · context
The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.
Summary · context
We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.
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-4026736504
05HumanNot a test of Liraglutide aloneObservational studyOther
In pooled metformin-treated GRADE T2D cohorts including liraglutide, weight gain at 1 year was associated with HbA1c-above 7.5% risk (HR 1.05, reported interval 1.04 to 1.07 per kilogram of weight change); no native-drug effect or exact weight reference was stated.
In plain wordsIn pooled T2D cohorts including liraglutide, first-year weight gain was linked to higher risk of HbA1c above 7.5%.
Peptide
Liraglutide
Outcome
IncreaseHbA1c above7.5% associated with first-year weight gain
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Measurements
Hazard ratio
1.05
HbA1c>7.5% per kilogram of weight change
Reported interval
1.04 to 1.07
HR; confidence level unstated in this sentence
Source sentences
Summary
Weight gain at 1 year was associated with increased risk of HbA1c >7.5% (HR 1.05 [1.04, 1.07]) and kidney disease (HR 1.03 [1.01, 1.06]).
2 context sentences(design, population, supporting numbers)
Summary · context
The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.
Summary · context
We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.
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-4026736505
06HumanNot a test of Liraglutide aloneObservational studyOther
In pooled metformin-treated GRADE T2D cohorts including liraglutide, weight gain at 1 year was associated with kidney disease (HR 1.03, reported interval 1.01 to 1.06 per kilogram of weight change); no native-drug effect or exact weight reference was stated.
In plain wordsIn pooled T2D cohorts including liraglutide, first-year weight gain was linked to higher kidney-disease risk.
Peptide
Liraglutide
Outcome
IncreaseKidney disease associated with first-year weight gain
Study
n: not reported in source
Outcome group
Kidney function · Kidney and urinary
Measurements
Hazard ratio
1.03
kidney disease per kilogram of weight change
Reported interval
1.01 to 1.06
HR; confidence level unstated in this sentence
Source sentences
Summary
Weight gain at 1 year was associated with increased risk of HbA1c >7.5% (HR 1.05 [1.04, 1.07]) and kidney disease (HR 1.03 [1.01, 1.06]).
2 context sentences(design, population, supporting numbers)
Summary · context
The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.
Summary · context
We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.
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-4026736506
07HumanNot a test of Liraglutide aloneObservational studyOther
In pooled metformin-treated GRADE T2D cohorts including liraglutide, baseline weight was associated with new-onset neuropathy; association direction and coefficient were unstated; no native-drug effect or exact weight reference was stated.
In plain wordsIn pooled T2D cohorts including liraglutide, baseline weight was linked to new neuropathy; the association direction was unstated.
Peptide
Liraglutide
Outcome
Direction not reportedNew-onset neuropathy association with baseline weight
Study
n: not reported in source
Outcome group
Adverse events · Nervous system and cognition
Source sentences
Summary
Baseline weight, but not weight gain, was associated with new-onset neuropathy.
2 context sentences(design, population, supporting numbers)
Summary · context
The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.
Summary · context
We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.
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-4026736507
08HumanNot a test of Liraglutide aloneObservational studyOther
In pooled metformin-treated GRADE T2D cohorts including liraglutide, weight gain was not associated with new-onset neuropathy; the association coefficient and statistical test were unstated; no native-drug effect or exact weight reference was stated.
In plain wordsIn pooled T2D cohorts including liraglutide, weight gain was not linked to new neuropathy; the statistical test was unstated.
Peptide
Liraglutide
Outcome
Not applicableNew-onset neuropathy association with weight gain
Study
n: not reported in source
Outcome group
Adverse events · Nervous system and cognition
Source sentences
Summary
Baseline weight, but not weight gain, was associated with new-onset neuropathy.
2 context sentences(design, population, supporting numbers)
Summary · context
The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.
Summary · context
We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.
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-4026736508
09HumanNot a test of Liraglutide aloneObservational studyOther
In pooled metformin-treated GRADE T2D cohorts including liraglutide, weight gain was associated with lower diabetes treatment satisfaction; the association coefficient was unstated; no native-drug effect or exact weight reference was stated.
In plain wordsIn pooled T2D cohorts including liraglutide, weight gain was linked to lower satisfaction with diabetes treatment.
Peptide
Liraglutide
Outcome
DecreaseDiabetes treatment satisfaction associated with weight gain
Study
n: not reported in source
Outcome group
Patient-reported outcomes · Whole body
Source sentences
Summary
Weight gain was associated with lower diabetes treatment satisfaction.
2 context sentences(design, population, supporting numbers)
Summary · context
The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D.
Summary · context
We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.
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-4026736509

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, 03:04 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

PepBank is a research reference. Talk to a doctor before you use any peptide.