Comparative Effectiveness of Glucagon-like Peptide-1 Receptor Agonists Versus Oral Agents for Insulin Discontinuation in Type 2 Diabetes : A Target Trial Emulation.

Lipska KJ, Zawack K, Yan L, Mutalik P, Li J, Gulanski B, Ioannou GN, Aslan M

Annals of internal medicine14 Jul 2026

PMID42441965DOI10.7326/annals-25-05216PepBankPUB-42441965

Publisher page PubMedAsk about this study

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 study16

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone16

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.

01HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide showed no significant insulin-discontinuation difference versus SGLT-2i over three years (16.7% versus 17.9%; RR 0.93, 95% CI 0.86 to 1.01).
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide showed no significant insulin-discontinuation difference versus SGLT-2i over three years.
Peptide
Semaglutide
Outcome
No significant changeInsulin discontinuation over 3 years
Study
n: not reported in source
Comparator
SGLT-2i initiators
Outcome group
Glycemic control · Metabolic and weight
Measurements
Insulin discontinuation
16.7%
GLP-1RA initiators; ITT; three-year follow-up
Insulin discontinuation
17.9%
SGLT-2i initiators; ITT; three-year follow-up
Discontinuations
1480 patients
GLP-1RA initiators; ITT; three-year follow-up
Discontinuations
1585 patients
SGLT-2i initiators; ITT; three-year follow-up
Risk ratio
0.93
GLP-1RA versus SGLT-2i; ITT; 95% CI 0.86 to 1.01
Source sentences
Summary
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
6 context sentences(design, population, supporting numbers)
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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.
Report a problemFND-4244196501
02HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide showed no significant insulin-discontinuation difference versus DPP-4i over three years (16.7% versus 17.1%; RR 0.98, 95% CI 0.87 to 1.09).
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide showed no significant insulin-discontinuation difference versus DPP-4i over three years.
Peptide
Semaglutide
Outcome
No significant changeInsulin discontinuation over 3 years
Study
n: not reported in source
Comparator
DPP-4i initiators
Outcome group
Glycemic control · Metabolic and weight
Measurements
Insulin discontinuation
16.7%
GLP-1RA initiators; ITT; three-year follow-up
Insulin discontinuation
17.1%
DPP-4i initiators; ITT; three-year follow-up
Discontinuations
1480 patients
GLP-1RA initiators; ITT; three-year follow-up
Discontinuations
1517 patients
DPP-4i initiators; ITT; three-year follow-up
Risk ratio
0.98
GLP-1RA versus DPP-4i; ITT; 95% CI 0.87 to 1.09
Source sentences
Summary
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
6 context sentences(design, population, supporting numbers)
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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.
Report a problemFND-4244196502
03HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide showed no significant insulin-discontinuation difference versus SGLT-2i over three years (16.7% versus 17.9%; RR 0.93, 95% CI 0.86 to 1.01).
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide showed no significant insulin-discontinuation difference versus SGLT-2i over three years.
Peptide
Liraglutide
Outcome
No significant changeInsulin discontinuation over 3 years
Study
n: not reported in source
Comparator
SGLT-2i initiators
Outcome group
Glycemic control · Metabolic and weight
Measurements
Insulin discontinuation
16.7%
GLP-1RA initiators; ITT; three-year follow-up
Insulin discontinuation
17.9%
SGLT-2i initiators; ITT; three-year follow-up
Discontinuations
1480 patients
GLP-1RA initiators; ITT; three-year follow-up
Discontinuations
1585 patients
SGLT-2i initiators; ITT; three-year follow-up
Risk ratio
0.93
GLP-1RA versus SGLT-2i; ITT; 95% CI 0.86 to 1.01
Source sentences
Summary
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
6 context sentences(design, population, supporting numbers)
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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-4244196503
04HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide showed no significant insulin-discontinuation difference versus DPP-4i over three years (16.7% versus 17.1%; RR 0.98, 95% CI 0.87 to 1.09).
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide showed no significant insulin-discontinuation difference versus DPP-4i over three years.
Peptide
Liraglutide
Outcome
No significant changeInsulin discontinuation over 3 years
Study
n: not reported in source
Comparator
DPP-4i initiators
Outcome group
Glycemic control · Metabolic and weight
Measurements
Insulin discontinuation
16.7%
GLP-1RA initiators; ITT; three-year follow-up
Insulin discontinuation
17.1%
DPP-4i initiators; ITT; three-year follow-up
Discontinuations
1480 patients
GLP-1RA initiators; ITT; three-year follow-up
Discontinuations
1517 patients
DPP-4i initiators; ITT; three-year follow-up
Risk ratio
0.98
GLP-1RA versus DPP-4i; ITT; 95% CI 0.87 to 1.09
Source sentences
Summary
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
6 context sentences(design, population, supporting numbers)
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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-4244196504
05HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide versus SGLT-2i showed that the modified per-protocol insulin-discontinuation comparison was reported as not substantively different from the intention-to-treat comparison.
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide versus SGLT-2i showed similar findings in the per-protocol analysis.
Peptide
Semaglutide
Outcome
Not applicableInsulin discontinuation in modified per-protocol analysis
Study
n: not reported in source
Comparator
SGLT-2i initiators
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Results were not substantively different in a modified per protocol analysis.
7 context sentences(design, population, supporting numbers)
Summary · context
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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.
Report a problemFND-4244196505
06HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide versus SGLT-2i showed that the modified per-protocol insulin-discontinuation comparison was reported as not substantively different from the intention-to-treat comparison.
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide versus SGLT-2i showed similar findings in the per-protocol analysis.
Peptide
Liraglutide
Outcome
Not applicableInsulin discontinuation in modified per-protocol analysis
Study
n: not reported in source
Comparator
SGLT-2i initiators
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Results were not substantively different in a modified per protocol analysis.
7 context sentences(design, population, supporting numbers)
Summary · context
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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-4244196506
07HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide versus SGLT-2i showed that no subgroup showed an insulin-discontinuation advantage.
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide versus SGLT-2i showed no subgroup insulin-discontinuation advantage.
Peptide
Semaglutide
Outcome
Not applicableInsulin discontinuation in subgroup analyses
Study
n: not reported in source
Comparator
SGLT-2i initiators
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
None of the subgroups showed a comparative advantage of GLP-1RAs with respect to insulin discontinuation over SGLT-2is or DPP-4is.
7 context sentences(design, population, supporting numbers)
Summary · context
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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.
Report a problemFND-4244196507
08HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide versus SGLT-2i showed that no subgroup showed an insulin-discontinuation advantage.
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide versus SGLT-2i showed no subgroup insulin-discontinuation advantage.
Peptide
Liraglutide
Outcome
Not applicableInsulin discontinuation in subgroup analyses
Study
n: not reported in source
Comparator
SGLT-2i initiators
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
None of the subgroups showed a comparative advantage of GLP-1RAs with respect to insulin discontinuation over SGLT-2is or DPP-4is.
7 context sentences(design, population, supporting numbers)
Summary · context
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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-4244196508
09HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide versus DPP-4i showed that the modified per-protocol insulin-discontinuation comparison was reported as not substantively different from the intention-to-treat comparison.
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide versus DPP-4i showed similar findings in the per-protocol analysis.
Peptide
Semaglutide
Outcome
Not applicableInsulin discontinuation in modified per-protocol analysis
Study
n: not reported in source
Comparator
DPP-4i initiators
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Results were not substantively different in a modified per protocol analysis.
7 context sentences(design, population, supporting numbers)
Summary · context
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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.
Report a problemFND-4244196509
10HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide versus DPP-4i showed that the modified per-protocol insulin-discontinuation comparison was reported as not substantively different from the intention-to-treat comparison.
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide versus DPP-4i showed similar findings in the per-protocol analysis.
Peptide
Liraglutide
Outcome
Not applicableInsulin discontinuation in modified per-protocol analysis
Study
n: not reported in source
Comparator
DPP-4i initiators
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Results were not substantively different in a modified per protocol analysis.
7 context sentences(design, population, supporting numbers)
Summary · context
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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-4244196510
11HumanNot a test of Semaglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide versus DPP-4i showed that no subgroup showed an insulin-discontinuation advantage.
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including semaglutide versus DPP-4i showed no subgroup insulin-discontinuation advantage.
Peptide
Semaglutide
Outcome
Not applicableInsulin discontinuation in subgroup analysis
Study
n: not reported in source
Comparator
DPP-4i initiators
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
None of the subgroups showed a comparative advantage of GLP-1RAs with respect to insulin discontinuation over SGLT-2is or DPP-4is.
7 context sentences(design, population, supporting numbers)
Summary · context
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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.
Report a problemFND-4244196511
12HumanNot a test of Liraglutide aloneObservational studyEfficacy outcome
In veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide versus DPP-4i showed that no subgroup showed an insulin-discontinuation advantage.
In plain wordsIn veterans with T2D on basal insulin, pooled GLP-1RAs including liraglutide versus DPP-4i showed no subgroup insulin-discontinuation advantage.
Peptide
Liraglutide
Outcome
Not applicableInsulin discontinuation in subgroup analysis
Study
n: not reported in source
Comparator
DPP-4i initiators
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
None of the subgroups showed a comparative advantage of GLP-1RAs with respect to insulin discontinuation over SGLT-2is or DPP-4is.
7 context sentences(design, population, supporting numbers)
Summary · context
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
Summary · context
Target trial emulation.
Summary · context
U.S.
Summary · context
Veterans Health Administration electronic health record (EHR) data.
Summary · context
Veterans with T2D receiving basal insulin.
Summary · context
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
Summary · context
Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A_1c (HbA1c</su…
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-4244196512
13HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In veterans with type 2 diabetes, pooled GLP-1RA initiation showed similar insulin discontinuation to SGLT-2i initiation.
In plain wordsIn veterans with diabetes, pooled GLP-1 drugs showed similar insulin discontinuation to SGLT-2 inhibitors.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeInsulin discontinuation versus SGLT-2 inhibitors
Study
n: not reported in source
Comparator
SGLT-2 inhibitors
Outcome group
Glycemic control · Metabolic and weight
Measurements
Risk ratio, GLP-1RA versus SGLT-2i
0.93 ratio
insulin discontinuation, intention-to-treat
95% CI of risk ratio
0.86 to 1.01 ratio
GLP-1RA versus SGLT-2i
Insulin discontinuation
16.7%
GLP-1RA initiators (1480)
Insulin discontinuation
17.9%
SGLT-2i initiators (1585)
Source sentences
Summary
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
2 context sentences(design, population, supporting numbers)
Summary · context
Target trial emulation.
Summary · context
Veterans Health Administration electronic health record (EHR) data.ParticipantsVeterans with T2D receiving basal insulin.
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).
Report a problemFND-4244196513
14HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In veterans with type 2 diabetes, pooled GLP-1RA initiation showed similar insulin discontinuation to DPP-4i initiation.
In plain wordsIn veterans with diabetes, pooled GLP-1 drugs showed similar insulin discontinuation to DPP-4 inhibitors.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeInsulin discontinuation versus DPP-4 inhibitors
Study
n: not reported in source
Comparator
DPP-4 inhibitors
Outcome group
Glycemic control · Metabolic and weight
Measurements
Risk ratio, GLP-1RA versus DPP-4i
0.98 ratio
insulin discontinuation, intention-to-treat
95% CI of risk ratio
0.87 to 1.09 ratio
GLP-1RA versus DPP-4i
Insulin discontinuation
16.7%
GLP-1RA initiators (1480)
Insulin discontinuation
17.1%
DPP-4i initiators (1517)
Source sentences
Summary
Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compare…
2 context sentences(design, population, supporting numbers)
Summary · context
Target trial emulation.
Summary · context
Veterans Health Administration electronic health record (EHR) data.ParticipantsVeterans with T2D receiving basal insulin.
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).
Report a problemFND-4244196514
15HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In veterans with diabetes, modified per-protocol results for pooled GLP-1RAs versus SGLT-2 inhibitors and DPP-4 inhibitors were not substantively different from the intention-to-treat results.
In plain wordsIn veterans with diabetes, per-protocol comparisons of pooled GLP-1 drugs with SGLT-2 and DPP-4 inhibitors gave similar results to the main analysis.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changePer-protocol insulin discontinuation
Study
n: not reported in source
Comparator
SGLT-2 inhibitors and DPP-4 inhibitors
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
Results were not substantively different in a modified per protocol analysis.
2 context sentences(design, population, supporting numbers)
Summary · context
Target trial emulation.
Summary · context
Veterans Health Administration electronic health record (EHR) data.ParticipantsVeterans with T2D receiving basal insulin.
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).
Report a problemFND-4244196515
16HumanNot a test of Dulaglutide (Trulicity) aloneObservational studyEfficacy outcome
In veterans with diabetes, no subgroup showed an insulin discontinuation advantage for pooled GLP-1RAs over SGLT-2 inhibitors or DPP-4 inhibitors.
In plain wordsIn veterans with diabetes, no subgroup favored pooled GLP-1 drugs over SGLT-2 or DPP-4 inhibitors for stopping insulin.
Peptide
Dulaglutide (Trulicity)
Outcome
No significant changeSubgroup insulin discontinuation
Study
n: not reported in source
Comparator
SGLT-2 inhibitors and DPP-4 inhibitors
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
None of the subgroups showed a comparative advantage of GLP-1RAs with respect to insulin discontinuation over SGLT-2is or DPP-4is.
2 context sentences(design, population, supporting numbers)
Summary · context
Target trial emulation.
Summary · context
Veterans Health Administration electronic health record (EHR) data.ParticipantsVeterans with T2D receiving basal insulin.
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).
Report a problemFND-4244196517

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.

Versions 5 to 10Current
28 Oct 2026, 02:03 UTC
The same notice was added 6 times, first on 22 Oct 2026, 02:26 UTC. The status did not change between them.
Study results updated
Version 4
21 Oct 2026, 18:59 UTC
Study data updated · source update from Europe PMC
Version 3
12 Oct 2026, 11:11 UTC
Study results updated
Version 2
9 Oct 2026, 03:06 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

Comparative Effectiveness of Glucagon-like Peptide-1 Receptor Agonists Versus Oral Agents for Insulin Discontinuation in Type 2 Diabetes : A Target Trial Emulation.

Summary

Results from this study16

Studies that did not test the peptide alone16

Version history

Subjects

Publication types

MeSH terms