Randomized open-label trial of semaglutide and dapagliflozin in patients with type 2 diabetes of different pathophysiology.

Dwibedi C, Ekström O, Brandt J, Adiels M, Franzén S, Abrahamsson B, Rosengren AH

Nature metabolism4 Jan 2024Cited by 28 (Europe PMC)

PMID38177805PMCIDPMC10822775DOI10.1038/s42255-023-00943-3PepBankPUB-38177805

Summary

The limited understanding of the heterogeneity in the treatment response to antidiabetic drugs contributes to metabolic deterioration and cardiovascular complications^1,2, stressing the need for more personalized treatment¹. Although recent attempts have been made to classify diabetes into subgroups, the utility of such stratification in predicting treatment response is unknown³. We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD). Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium-glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label). The primary endpoint was the change in glycated haemoglobin (HbA1c). Semaglutide induced a larger reduction in HbA1c levels than dapagliflozin (mean difference, 8.2 mmol mol^-1; 95% confidence interval, -10.0 to -6.3 mmol mol^-1), with a pronounced effect in those with SIDD. No difference in adverse events was observed between participants with SIDD and those with SIRD. Analysis of secondary endpoints showed greater reductions in fasting and postprandial glucose concentrations in response to semaglutide in participants with SIDD than in those with SIRD and a more pronounced effect on postprandial glucose by dapagliflozin in participants with SIDD than in those with SIRD. However, no significant interaction was found between drug assignment and the SIDD or SIRD subgroup. In contrast, continuous measures of body mass index, blood pressure, insulin secretion and insulin resistance were useful in identifying those likely to have the largest improvements in glycaemic control and cardiovascular risk factors by adding semaglutide or dapagliflozin. Thus, systematic evaluation of continuous pathophysiological variables can guide the prediction of the treatment response to these drugs and provide more information than stratified subgroups ( NCT04451837 ).

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

Results from this study7

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

01HumanRandomized controlled trialEfficacy outcome
In adults with severe insulin-deficient or insulin-resistant type 2 diabetes, semaglutide reduced HbA1c more than dapagliflozin over 6 months (mean difference 8.2 mmol/mol).
In plain wordsIn adults with type 2 diabetes, semaglutide lowered HbA1c more than dapagliflozin over 6 months.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change
Study
n = 239
Comparator
Dapagliflozin
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Measurements
Mean difference in HbA1c
8.2 mmol/mol
semaglutide vs dapagliflozin
Source sentences
Summary
Semaglutide induced a larger reduction in HbA1c levels than dapagliflozin (mean difference, 8.2 mmol mol^-1; 95% confidence interval, -10.0 to -6.3 mmol mol^-1), with a pronounced effect in those with SIDD.
3 context sentences(design, population, supporting numbers)
Summary · context
The primary endpoint was the change in glycated haemoglobin (HbA1c).
Summary · context
We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD).
Summary · context
Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium-glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label).
Show in the study text Report a problemFND-3817780501
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, semaglutide reduced fasting glucose more in participants with SIDD than in those with SIRD.
In plain wordsIn adults with type 2 diabetes, semaglutide lowered fasting glucose more in people with severe insulin deficiency than in those with severe insulin resistance.
Peptide
Semaglutide
Outcome
DecreaseFasting glucose reduction, SIDD versus SIRD
Study
n: not reported in source
Comparator
SIRD subgroup
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Source sentences
Summary
greater reductions in fasting and postprandial glucose concentrations in response to semaglutide in participants with SIDD than in those with SIRD
2 context sentences(design, population, supporting numbers)
Summary · context
We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD).
Summary · context
Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium-glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label).
Show in the study text Report a problemFND-3817780503
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes, semaglutide reduced postprandial glucose more in participants with SIDD than in those with SIRD.
In plain wordsIn adults with type 2 diabetes, semaglutide lowered after-meal glucose more in people with severe insulin deficiency than in those with severe insulin resistance.
Peptide
Semaglutide
Outcome
DecreasePostprandial glucose reduction, SIDD versus SIRD
Study
n: not reported in source
Comparator
SIRD subgroup
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Source sentences
Summary
greater reductions in fasting and postprandial glucose concentrations in response to semaglutide in participants with SIDD than in those with SIRD
2 context sentences(design, population, supporting numbers)
Summary · context
We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD).
Summary · context
Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium-glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label).
Show in the study text Report a problemFND-3817780504
04HumanRandomized controlled trialEfficacy outcome
In adults with severe insulin-deficient diabetes, the HbA1c reduction with semaglutide was pronounced.
In plain wordsIn adults with severe insulin-deficient type 2 diabetes, semaglutide lowered HbA1c especially strongly.
Peptide
Semaglutide
Outcome
DecreaseHbA1c reduction in severe insulin-deficient diabetes
Study
n: not reported in source
Comparator
Dapagliflozin
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 6 monthsAs given in this study (human).
Source sentences
Summary
with a pronounced effect in those with SIDD.
2 context sentences(design, population, supporting numbers)
Summary · context
We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD).
Summary · context
Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium-glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label).
Show in the study text Report a problemFND-3817780502

Studies that did not test the peptide alone3

In this study, Semaglutide 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 Semaglutide.

05HumanNot a test of Semaglutide aloneRandomized controlled trialSafety outcome
In adults with type 2 diabetes treated with semaglutide or dapagliflozin, adverse events did not differ between the SIDD and SIRD subgroups.
In plain wordsIn adults with type 2 diabetes on semaglutide or dapagliflozin, side effects were no different between the two diabetes subgroups.
Peptide
Semaglutide
Outcome
No significant changeAdverse events, SIDD versus SIRD
Study
n = 239
Comparator
SIRD subgroup
Outcome group
Adverse events · Whole body
Source sentences
Summary
No difference in adverse events was observed between participants with SIDD and those with SIRD.
2 context sentences(design, population, supporting numbers)
Summary · context
We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD).
Summary · context
Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium-glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label).
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-3817780505
06HumanNot a test of Semaglutide aloneRandomized controlled trialOther
In adults with type 2 diabetes, no significant interaction was found between assignment to semaglutide or dapagliflozin and the SIDD or SIRD subgroup.
In plain wordsIn adults with type 2 diabetes, the diabetes subgroup did not significantly change which of the two drugs worked better.
Peptide
Semaglutide
Outcome
No significant changeInteraction between drug assignment and diabetes subgroup
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
However, no significant interaction was found between drug assignment and the SIDD or SIRD subgroup.
2 context sentences(design, population, supporting numbers)
Summary · context
We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD).
Summary · context
Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium-glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label).
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-3817780506
07HumanNot a test of Semaglutide aloneRandomized controlled trialOther
In adults with type 2 diabetes, BMI, blood pressure, insulin secretion and insulin resistance identified those with the largest improvement when semaglutide or dapagliflozin was added.
In plain wordsIn adults with type 2 diabetes, body mass index, blood pressure and insulin measures pointed to who gained most from semaglutide or dapagliflozin.
Peptide
Semaglutide
Outcome
Not applicableContinuous measures that identify larger glycaemic improvement
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
In contrast, continuous measures of body mass index, blood pressure, insulin secretion and insulin resistance were useful in identifying those likely to have the largest improvements in glycaemic control and cardiovascular risk factors by adding semaglutide or dapagliflozin.
2 context sentences(design, population, supporting numbers)
Summary · context
We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD).
Summary · context
Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium-glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label).
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-3817780507

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 ongoing · source ClinicalTrials.gov (opens in a new tab)

Active, not recruitingPhase 2NCT04451837

Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology

Region Skanen = 20010 Sept 2020 to est. 31 Dec 2026

Type2 Diabetes

Trial page ClinicalTrials.govUpdated 16 Jul 2025

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
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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