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Study · Randomized controlled trial · n = 24 · 2026

9 results

Dulaglutide versus empagliflozin as add-on therapy to metformin and sulfonylurea in type 2 diabetes: a randomized pilot study with exploratory metabolomic and microbiome analyses.

Jun JE, Oh DH, Jeong IK, Ryu HJ, Hwang YC, Ahn KJ, Chung HY, Kim KP

Frontiers in endocrinology17 Jun 2026

PMID42388875 (opens in a new tab)PMCIDPMC13318618 (opens in a new tab)DOI10.3389/fendo.2026.1843595 (opens in a new tab)PepBankPUB-42388875
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Summary

In patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and sulfonylurea, evidence directly comparing glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors as add-on therapy is limited; therefore, we compared dulaglutide and empagliflozin in this setting. This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension. Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day. Doses were uptitrated at week 4 if tolerated and maintained for 12 weeks, with follow-up until week 36. The primary endpoint was the change in HbA1c at week 12. Secondary endpoints included changes in glycemic and obesity-related parameters. Exploratory analyses were performed to assess plasma metabolite profiles using liquid chromatography-mass spectrometry, and gut microbiota using 16S rRNA gene sequencing. Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11). Both treatments significantly reduced HbA1c at week 12, with no significant between-group difference. Empagliflozin significantly reduced HOMA-IR, whereas dulaglutide significantly increased HOMA-β. At week 12, empagliflozin was associated with greater reductions in body weight and body fat compared with dulaglutide, whereas these differences were attenuated at week 36. Exploratory analyses suggested potential, modest treatment-related differences in plasma metabolite profiles and microbiome-metabolic associations, without marked alterations in overall microbial diversity. As add-on therapy to metformin and sulfonylurea, both dulaglutide and empagliflozin improved glycemic control, with no significant between-group difference observed in this exploratory pilot study. Empagliflozin induced earlier weight loss, whereas dulaglutide showed more gradual weight reduction over time, accompanied by exploratory findings suggesting possible differences in plasma and microbiome-related metabolic signatures.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

7 results from studies that gave the peptide. 7 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In T2DM on metformin and glimepiride, HbA1c reduction did not differ significantly between dulaglutide and empagliflozin at week 12.

    In plain wordsIn people with diabetes, dulaglutide and empagliflozin did not differ significantly in HbA1c reduction.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    No significant changeHbA1c between treatments
    Study

    n = 24

    Comparator
    empagliflozin
    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    0.75 mg/week (uptitrated at week 4 if tolerated) · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Both treatments significantly reduced HbA1c at week 12, with no significant between-group difference.
    3 context sentences
    Summary · context
    This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension.
    Summary · context
    Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day.
    Summary · context
    Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11).
  2. 02HumanRandomized controlled trialEfficacy outcome

    In T2DM, dulaglutide produced less body weight reduction than empagliflozin at week 12.

    In plain wordsIn people with diabetes, dulaglutide reduced weight less than empagliflozin at week 12.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    IncreaseBody weight at week 12
    Study

    n = 24

    Comparator
    empagliflozin
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    0.75 mg/week (uptitrated at week 4 if tolerated) · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    At week 12, empagliflozin was associated with greater reductions in body weight and body fat compared with dulaglutide, whereas these differences were attenuated at week 36.
    3 context sentences
    Summary · context
    This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension.
    Summary · context
    Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day.
    Summary · context
    Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11).
  3. 03HumanRandomized controlled trialEfficacy outcome

    In T2DM, dulaglutide produced less body fat reduction than empagliflozin at week 12.

    In plain wordsIn people with diabetes, dulaglutide reduced body fat less than empagliflozin at week 12.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    IncreaseBody fat at week 12
    Study

    n = 24

    Comparator
    empagliflozin
    Analysis
    Secondary
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    0.75 mg/week (uptitrated at week 4 if tolerated) · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    At week 12, empagliflozin was associated with greater reductions in body weight and body fat compared with dulaglutide, whereas these differences were attenuated at week 36.
    3 context sentences
    Summary · context
    This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension.
    Summary · context
    Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day.
    Summary · context
    Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11).
  4. 04HumanRandomized controlled trialEfficacy outcome

    In T2DM, exploratory analyses suggested potential modest differences between dulaglutide and empagliflozin in plasma metabolite profiles and microbiome-metabolic associations.

    In plain wordsIn people with diabetes, exploratory tests suggested modest metabolic profile differences between dulaglutide and empagliflozin.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    Direction not reportedPlasma metabolite profiles and microbiome associations
    Study

    n = 24

    Comparator
    empagliflozin
    Analysis
    Exploratory
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    0.75 mg/week (uptitrated at week 4 if tolerated) · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Exploratory analyses suggested potential, modest treatment-related differences in plasma metabolite profiles and microbiome-metabolic associations, without marked alterations in overall microbial diversity.
    3 context sentences
    Summary · context
    This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension.
    Summary · context
    Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day.
    Summary · context
    Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11).
  5. 05HumanRandomized controlled trialEfficacy outcome

    In T2DM on metformin and glimepiride, dulaglutide significantly increased HOMA-β.

    In plain wordsIn people with diabetes on metformin and glimepiride, dulaglutide increased the HOMA-β measure of insulin secretion.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    IncreaseHOMA-β
    Study

    n = 13

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    0.75 mg/week (uptitrated at week 4 if tolerated) · 12 weeksAs given in this study (human).

    Source sentences

    Summary
    Empagliflozin significantly reduced HOMA-IR, whereas dulaglutide significantly increased HOMA-β.
    3 context sentences
    Summary · context
    This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension.
    Summary · context
    Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day.
    Summary · context
    Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11).
  6. 06HumanObservational studyEfficacy outcome

    In the T2DM observational extension, the body weight reduction difference between dulaglutide and empagliflozin attenuated at week 36.

    In plain wordsIn the diabetes study extension, the weight reduction difference between dulaglutide and empagliflozin became smaller at week 36.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    Direction not reportedBody weight at week 36
    Study

    n: not reported in source

    Comparator
    empagliflozin
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    0.75 mg/week (uptitrated at week 4 if tolerated) · 12 weeks treatment, follow-up until week 36As given in this study (human).

    Source sentences

    Summary
    At week 12, empagliflozin was associated with greater reductions in body weight and body fat compared with dulaglutide, whereas these differences were attenuated at week 36.
    3 context sentences
    Summary · context
    This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension.
    Summary · context
    Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day.
    Summary · context
    Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11).
  7. 07HumanObservational studyEfficacy outcome

    In the T2DM observational extension, the body fat reduction difference between dulaglutide and empagliflozin attenuated at week 36.

    In plain wordsIn the diabetes study extension, the body fat reduction difference between dulaglutide and empagliflozin became smaller at week 36.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    Direction not reportedBody fat at week 36
    Study

    n: not reported in source

    Comparator
    empagliflozin
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    0.75 mg/week (uptitrated at week 4 if tolerated) · 12 weeks treatment, follow-up until week 36As given in this study (human).

    Source sentences

    Summary
    At week 12, empagliflozin was associated with greater reductions in body weight and body fat compared with dulaglutide, whereas these differences were attenuated at week 36.
    3 context sentences
    Summary · context
    This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension.
    Summary · context
    Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day.
    Summary · context
    Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11).

Studies that did not test the peptide alone2

In this study, Dulaglutide (Trulicity) 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 Dulaglutide (Trulicity).

  1. 08HumanNot a test of Dulaglutide (Trulicity) aloneRandomized controlled trialEfficacy outcome

    In T2DM on metformin and glimepiride, HbA1c decreased significantly from baseline with both dulaglutide and empagliflozin at week 12.

    In plain wordsIn people with diabetes, HbA1c decreased from baseline with both dulaglutide and empagliflozin.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    DecreaseHbA1c change
    Study

    n = 24

    Analysis
    Primary
    Outcome group
    Glycemic control · Metabolic and weight

    Source sentences

    Summary
    Both treatments significantly reduced HbA1c at week 12, with no significant between-group difference.
    3 context sentences
    Summary · context
    This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension.
    Summary · context
    Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day.
    Summary · context
    Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11).

    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).

  2. 09HumanNot a test of Dulaglutide (Trulicity) aloneRandomized controlled trialEfficacy outcome

    In the T2DM trial comparing dulaglutide and empagliflozin, exploratory analysis found no marked overall microbial diversity alterations.

    In plain wordsIn people with diabetes, exploratory analysis found no marked microbial diversity changes in the dulaglutide and empagliflozin trial.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    Direction not reportedOverall microbial diversity
    Study

    n = 24

    Analysis
    Exploratory
    Outcome group
    Receptor activity and mechanism · Metabolic and weight

    Source sentences

    Summary
    Exploratory analyses suggested potential, modest treatment-related differences in plasma metabolite profiles and microbiome-metabolic associations, without marked alterations in overall microbial diversity.
    3 context sentences
    Summary · context
    This 12-week, single-center, randomized, open-label, parallel-group pilot study included a 24-week observational extension.
    Summary · context
    Patients with HbA1c≥7.0% receiving stable doses of metformin and glimepiride were randomized to dulaglutide 0.75 mg/week or empagliflozin 10 mg/day.
    Summary · context
    Twenty-four patients completed the 12-week study (dulaglutide, n=13; empagliflozin, n=11).

    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).

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.

  1. Version 2Current

    22 Oct 2026, 02:25 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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