Is Weight Loss the Main Driver for A1C Improvement by Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists? A 2.5-Year Analysis in Real-World Clinical Practice.

Al-Badri M, Dhaver S, Hamdy O

Journal of diabetes1 Jan 2025

PMID39853913PMCIDPMC11757277DOI10.1111/1753-0407.70054PepBankPUB-39853913

Summary

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, GLP-1 RAs also induce weight loss by suppressing appetite via hypothalamic pathways. However, it remains unclear whether weight reduction is the primary driver of glycemic improvement.MethodsWe retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice. Body weight and A1C were measured every 6 months. Baseline characteristics included an average age of 61.8 ± 11.9 years, 51.5% female, diabetes duration of 12.9 ± 8.3 years, weight of 103.1 ± 20.7 kg, BMI of 35.7 ± 7.5 kg/m², and A1C of 8.2% ± 1.5%. Patients were stratified into tertiles based on percentage weight change at 2.5 years within the overall cohort and for each GLP-1 RA group.ResultsThe first tertile experienced an average weight loss of -12.2% ± 5.7% (p < 0.0001), the second tertile lost -3.5% ± 1.4% (p < 0.0001), and the third tertile gained +2.8% ± 3.4% (p < 0.0001). The average changes in A1C were - 0.98 ± 1.8% (p < 0.0001), -0.56% ± 1.4% (p < 0.001), and -0.19% ± 1.9% (p = 0.4), respectively. A1C strongly correlated with weight change (p < 0.001). The same observations were reproducible in each medication group.ConclusionsThese findings suggest that the long-term improvement in glycemic control associated with GLP-1 RA therapy is primarily driven by weight loss rather than any other intrinsic effect of GLP-1 RA. This highlights the importance of weight reduction as a key therapeutic target for optimizing glycemic outcomes in patients with T2D receiving GLP-1 RAs.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study16

1 result from studies that gave the peptide. 1 result from people.

01HumanObservational studyOther
In patients with T2D receiving semaglutide, A1C correlated with weight change, reproducing the pooled observation.
In plain wordsIn patients with diabetes receiving semaglutide, A1C was linked to weight change.
Peptide
Semaglutide
Outcome
Not applicableA1C association with weight change
Study
n = 73
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 2.5 yearsAs given in this study (human).
Source sentences
Summary
A1C strongly correlated with weight change (p < 0.001). The same observations were reproducible in each medication group.
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
Show in the study text Report a problemFND-3985391314

Studies that did not test the peptide alone15

In this study, the peptide 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 the peptide.

02HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyOther
In the pooled T2D cohort receiving exenatide, dulaglutide or semaglutide, A1C strongly correlated with weight change.
In plain wordsIn patients receiving pooled drugs including dulaglutide and semaglutide, A1C was strongly linked to weight change.
Peptide
Dulaglutide (Trulicity)
Outcome
Not applicablePooled A1C association with weight change
Study
n = 256
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
A1C strongly correlated with weight change (p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).
Show in the study text Report a problemFND-3985391315
03HumanNot a test of Semaglutide aloneObservational studyOther
In the pooled T2D cohort receiving exenatide, dulaglutide or semaglutide, A1C strongly correlated with weight change.
In plain wordsIn patients receiving pooled drugs including dulaglutide and semaglutide, A1C was strongly linked to weight change.
Peptide
Semaglutide
Outcome
Not applicablePooled A1C association with weight change
Study
n = 256
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
A1C strongly correlated with weight change (p < 0.001).
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3985391316
04HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyOther
In patients with T2D receiving dulaglutide, A1C correlated with weight change, reproducing the pooled observation.
In plain wordsIn patients with diabetes receiving dulaglutide, A1C was linked to weight change.
Peptide
Dulaglutide (Trulicity)
Outcome
Not applicableA1C association with weight change
Study
n = 99
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
A1C strongly correlated with weight change (p < 0.001). The same observations were reproducible in each medication group.
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).
Show in the study text Report a problemFND-3985391313
05HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In patients with T2D, pooled GLP-1 RA use including dulaglutide was linked to weight loss in the first tertile.
In plain wordsIn patients with diabetes, pooled drugs including dulaglutide were linked to weight loss in the first tertile.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseWeight change, first tertile
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Weight change
−12.2%
first tertile of weight change, pooled GLP-1 RAs, 2.5 years
Source sentences
Summary
The first tertile experienced an average weight loss of -12.2% ± 5.7% (p < 0.0001), the second tertile lost -3.5% ± 1.4% (p < 0.0001), and the third tertile gained +2.8% ± 3.4% (p < 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).
Show in the study text Report a problemFND-3985391301
06HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In patients with T2D, pooled GLP-1 RA use including semaglutide was linked to weight loss in the first tertile.
In plain wordsIn patients with diabetes, pooled drugs including semaglutide were linked to weight loss in the first tertile.
Peptide
Semaglutide
Outcome
DecreaseWeight change, first tertile
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Weight change
−12.2%
first tertile of weight change, pooled GLP-1 RAs, 2.5 years
Source sentences
Summary
The first tertile experienced an average weight loss of -12.2% ± 5.7% (p < 0.0001), the second tertile lost -3.5% ± 1.4% (p < 0.0001), and the third tertile gained +2.8% ± 3.4% (p < 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3985391302
07HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In patients with T2D, pooled GLP-1 RAs including dulaglutide were linked to weight loss in the second tertile.
In plain wordsIn patients with diabetes, pooled drugs including dulaglutide were linked to weight loss in the second tertile.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseWeight change, second tertile
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Weight change
−3.5%
second tertile of weight change, pooled GLP-1 RAs, 2.5 years
Source sentences
Summary
The first tertile experienced an average weight loss of -12.2% ± 5.7% (p < 0.0001), the second tertile lost -3.5% ± 1.4% (p < 0.0001), and the third tertile gained +2.8% ± 3.4% (p < 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).
Show in the study text Report a problemFND-3985391303
08HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In patients with T2D, pooled GLP-1 RAs including semaglutide were linked to weight loss in the second tertile.
In plain wordsIn patients with diabetes, pooled drugs including semaglutide were linked to weight loss in the second tertile.
Peptide
Semaglutide
Outcome
DecreaseWeight change, second tertile
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Weight change
−3.5%
second tertile of weight change, pooled GLP-1 RAs, 2.5 years
Source sentences
Summary
The first tertile experienced an average weight loss of -12.2% ± 5.7% (p < 0.0001), the second tertile lost -3.5% ± 1.4% (p < 0.0001), and the third tertile gained +2.8% ± 3.4% (p < 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3985391304
09HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In patients with T2D on pooled GLP-1 RAs including dulaglutide, the third tertile of weight change gained a mean of 2.8% body weight at 2.5 years.
In plain wordsAmong patients with diabetes on pooled drugs including dulaglutide, the third who gained weight gained 2.8% on average.
Peptide
Dulaglutide (Trulicity)
Outcome
IncreaseWeight change, third tertile
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Weight change
2.8%
third tertile of weight change, pooled GLP-1 RAs, 2.5 years
Source sentences
Summary
The first tertile experienced an average weight loss of -12.2% ± 5.7% (p < 0.0001), the second tertile lost -3.5% ± 1.4% (p < 0.0001), and the third tertile gained +2.8% ± 3.4% (p < 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).
Show in the study text Report a problemFND-3985391305
10HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In patients with T2D on pooled GLP-1 RAs including semaglutide, the third tertile of weight change gained a mean of 2.8% body weight at 2.5 years.
In plain wordsAmong patients with diabetes on pooled drugs including semaglutide, the third who gained weight gained 2.8% on average.
Peptide
Semaglutide
Outcome
IncreaseWeight change, third tertile
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Measurements
Weight change
2.8%
third tertile of weight change, pooled GLP-1 RAs, 2.5 years
Source sentences
Summary
The first tertile experienced an average weight loss of -12.2% ± 5.7% (p < 0.0001), the second tertile lost -3.5% ± 1.4% (p < 0.0001), and the third tertile gained +2.8% ± 3.4% (p < 0.0001).
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3985391306
11HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In patients with T2D, pooled GLP-1 RAs including dulaglutide were linked to lower A1C in the first tertile.
In plain wordsIn patients with diabetes, pooled drugs including dulaglutide were linked to lower A1C in the first tertile.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseA1C change, first tertile
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Measurements
A1C change
−0.98%
first weight-change tertile, pooled GLP-1 RAs
Source sentences
Summary
The average changes in A1C were - 0.98 ± 1.8% (p < 0.0001), -0.56% ± 1.4% (p < 0.001), and -0.19% ± 1.9% (p = 0.4), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).
Show in the study text Report a problemFND-3985391307
12HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In patients with T2D, pooled GLP-1 RAs including semaglutide were linked to lower A1C in the first tertile.
In plain wordsIn patients with diabetes, pooled drugs including semaglutide were linked to lower A1C in the first tertile.
Peptide
Semaglutide
Outcome
DecreaseA1C change, first tertile
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Measurements
A1C change
−0.98%
first weight-change tertile, pooled GLP-1 RAs
Source sentences
Summary
The average changes in A1C were - 0.98 ± 1.8% (p < 0.0001), -0.56% ± 1.4% (p < 0.001), and -0.19% ± 1.9% (p = 0.4), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3985391308
13HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In patients with T2D, pooled GLP-1 RAs including dulaglutide were linked to lower A1C in the second tertile.
In plain wordsIn patients with diabetes, pooled drugs including dulaglutide were linked to lower A1C in the second tertile.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseA1C change, second tertile
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Measurements
A1C change
−0.56%
second weight-change tertile, pooled GLP-1 RAs
Source sentences
Summary
The average changes in A1C were - 0.98 ± 1.8% (p < 0.0001), -0.56% ± 1.4% (p < 0.001), and -0.19% ± 1.9% (p = 0.4), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).
Show in the study text Report a problemFND-3985391309
14HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In patients with T2D, pooled GLP-1 RAs including semaglutide were linked to lower A1C in the second tertile.
In plain wordsIn patients with diabetes, pooled drugs including semaglutide were linked to lower A1C in the second tertile.
Peptide
Semaglutide
Outcome
DecreaseA1C change, second tertile
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Measurements
A1C change
−0.56%
second weight-change tertile, pooled GLP-1 RAs
Source sentences
Summary
The average changes in A1C were - 0.98 ± 1.8% (p < 0.0001), -0.56% ± 1.4% (p < 0.001), and -0.19% ± 1.9% (p = 0.4), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3985391310
15HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In patients with T2D, A1C did not change significantly in the third tertile with pooled GLP-1 RAs including dulaglutide.
In plain wordsIn patients with diabetes, A1C did not change significantly in the third tertile with pooled drugs including dulaglutide.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeA1C change, third tertile
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Measurements
A1C change
−0.19%
third weight-change tertile, pooled GLP-1 RAs
Source sentences
Summary
The average changes in A1C were - 0.98 ± 1.8% (p < 0.0001), -0.56% ± 1.4% (p < 0.001), and -0.19% ± 1.9% (p = 0.4), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).
Show in the study text Report a problemFND-3985391311
16HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In patients with T2D, A1C did not change significantly in the third tertile with pooled GLP-1 RAs including semaglutide.
In plain wordsIn patients with diabetes, A1C did not change significantly in the third tertile with pooled drugs including semaglutide.
Peptide
Semaglutide
Outcome
No significant changeA1C change, third tertile
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Measurements
A1C change
−0.19%
third weight-change tertile, pooled GLP-1 RAs
Source sentences
Summary
The average changes in A1C were - 0.98 ± 1.8% (p < 0.0001), -0.56% ± 1.4% (p < 0.001), and -0.19% ± 1.9% (p = 0.4), respectively.
1 context sentence(design, population, supporting numbers)
Summary · context
We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3985391312

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

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 3Current
22 Oct 2026, 02:25 UTC
Study results updated
Version 2
21 Oct 2026, 18:59 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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Is Weight Loss the Main Driver for A1C Improvement by Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists? A 2.5-Year Analysis in Real-World Clinical Practice.

Summary

Results from this study16

Studies that did not test the peptide alone15

Version history

Subjects

Publication types

MeSH terms

Keywords