Diabetes Mellitus, Type 2NCT06120556
Efficacy of Glucagon-like Peptide-1 Receptor Agonists According to Type 2 Diabetes Subtypes
An observational study of Diabetes Mellitus, Type 2, run by Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari at 1 site in Italy.
Trial summary
The goal of this observational retrospective study is to understand whether glucagon-like peptide-1 receptor agonists (GLP-1RA), which are a group of antidiabetes drugs, may act differently in different subtypes of patients with type 2 diabetes. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- GLP-1 receptor agonist
- How many people
- 130 participants
- Where
- 1 siteItaly
- Study dates
- 10 Jun 2023to 31 Oct 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All patients who attended the Day Service for diabetes of the Endocrinology Unit of the University Hospital A.O.U. Policlinico di Bari, Puglia, Italy from January 1st 2012 to October 1st 2023 will be consecutively evaluated for inclusion.
Who may be able to join
- Italian patients with type 2 diabetes
- Onset of diabetes at ≥ 50 years
- Diagnosis of type 2 diabetes ≤ 5 years from enrollment
- BMI ≥ 25 kg/m2
- Patients receiving a GLP-1RA prescription for the first time with at least one follow-up visit at 6-12 months from first prescription
Who cannot join
- Autoimmune diabetes, monogenic diabetes, secondary diabetes
- History of diabetic ketoacidosis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of Glucagon-like Peptide-1 Receptor Agonists According to Type 2 Diabetes Subtypes: an Italian Monocentric Retrospective Study
The goal of this observational retrospective study is to understand whether glucagon-like peptide-1 receptor agonists (GLP-1RA), which are a group of antidiabetes drugs, may act differently in different subtypes of patients with type 2 diabetes.
The main questions it aims to answer are:
Read more
- people with type 2 diabetes belonging to specific subtypes respond better (or worse) to GLP-1RA?
- the beneficial effect of GLP-1RA may last longer in people with type 2 diabetes belonging to specific subtypes?
- what are the clinical characteristics that better explain the efficacy and durability of GLP-1 receptor agonists in type 2 diabetes management?
Clinical data from records of patients attending the diabetes outpatient clinic of our facility will be retrieved to compare the outcomes of GLP-1 receptor agonists in patients belonging to four subtypes of type 2 diabetes.
Read the detailed description
Patients with type 2 diabetes are all characterized by hyperglycemia, however their probability to develop micro- and micro-vascular complications. A classification of adult-onset diabetes in 5 subtypes was recently proposed: severe autoimmune diabetes (SAID - including type 1 diabetes and latent autoimmune diabetes in adults LADA), severe insulin resistant diabetes (SIRD), severe insulin deficient diabetes (SIDD), mild age related diabetes (MARD), mild obesity-related diabetes (MOD). This classification has been validated in a multiple populations of patients with recent onset diabetes (within 5 years).
However, this classification requires the measurement of c-peptide/insulinemia or anti- glutamic acid decarboxylase (GAD) antibodies, limiting its applicability in everyday clinical practice. An alternative algorithm requiring easily available clinical characteristics, such as BMI, height, waist circumference, HbA1c, fasting blood glucose, lipid profile, age and age at diagnosis was recently introduced and validated.
In this retrospective observational study, the calculated sample size was of 128 patients, in 4 groups, with alpha 0.05, 1-beta 0.80, effect size 0.3.
The following data will be retrieved for eligible patients: age, sex, diabetes duration, age at diagnosis, antidiabetes therapy, body weight, height, waist circumference, fasting blood glucose, HbA1c, total and HDL and LDL cholesterol, triglycerides, creatinine, microalbuminuria. The algorithm available online (https://uiem.shinyapps.io/diabetes_clusters_app/), will be used to assign enrolled patients to the 4 subtypes of type 2 diabetes (SIDD, SIRD, MARD, MOD).
If available, information regarding micro- and macro-vascular complications of diabetes will be retrieved.
All data will be collected at baseline visit and every follow-up visit (the first follow-up visit should 6-12 months following prescription of a GLP-1 receptor agonist).
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- GLP-1 receptor agonist
- Keywords
- type 2 diabetes, GLP-1 receptor agonists, subtypes, phenotypes
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLP-1 receptor agonistDrug
Patients initiating a GLP-1 receptor agonist (i.e. liraglutide, dulaglutide, semaglutide) will be included in the study.
| Study group | Role | What they receive |
|---|---|---|
| Severe Insulin Resistant Diabetes (SIRD) | Patients with SIRD are characterized by high BMI and high insulin resistance and low HbA1c. These patients likely develop diabetic kidney disease.
Defined according to the simplified algorithm proposed by Bello-Chavolla et al. requiring the following data: age at diabetes diagnosis, age, BMI, height, waist circumference, HbA1c, fasting blood glucose, fasting triglycerides, HDL cholesterol Receives: Drug: GLP-1 receptor agonist | |
| Mild Age-Related Diabetes (MARD) | Patients with MARD are characterized by late onset diabetes without extreme features.
Defined according to the simplified algorithm proposed by Bello-Chavolla et al. requiring the following data: age at diabetes diagnosis, age, BMI, height, waist circumference, HbA1c, fasting blood glucose, fasting triglycerides, HDL cholesterol Receives: Drug: GLP-1 receptor agonist | |
| Mild Obesity-related Diabetes (MOD) | Patients with MOD are characterized by high BMI without insulin resistance. Defined according to the simplified algorithm proposed by Bello-Chavolla et al. requiring the following data: age at diabetes diagnosis, age, BMI, height, waist circumference, HbA1c, fasting blood glucose, fasting triglycerides, HDL cholesterol Receives: Drug: GLP-1 receptor agonist | |
| Severe Insulin Deficient Diabetes (SIDD) | Patients with SIDD are characterized by high HbA1c and rapid progression to insulin therapy. These patients likely develop retinopathy, even in the first years after diagnosis.
Defined according to the simplified algorithm proposed by Bello-Chavolla et al. requiring the following data: age at diabetes diagnosis, age, BMI, height, waist circumference, HbA1c, fasting blood glucose, fasting triglycerides, HDL cholesterol Receives: Drug: GLP-1 receptor agonist |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in HbA1c change from baseline (%) among SIDD, SIRD, MARD, MOD subtypes
Measured: Difference in HbA1c change from baseline will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Secondary outcomes (4)
Difference in time to failure among SIDD, SIRD, MARD, MOD subtypes
In patients reaching HbA1c <7% at first follow-up visit, the difference in time to failure (defined as HbA1c equal or above 7%)
Measured: Difference in time to failure will be assessed up to the last available visit (up to 36 months)
Difference in fasting blood glucose change from baseline (mg/dl) among SIDD, SIRD, MARD, MOD subtypes
mg/dl
Measured: Difference in fasting blood glucose change from baseline (mg/dl) will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Difference in body weight change from baseline (kg) among SIDD, SIRD, MARD, MOD subtypes
kg
Measured: Difference in body weight change from baseline (kg) will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Difference in percentage of patients reaching HbA1c below 7% among SIDD, SIRD, MARD, MOD subtypes
Measured: Difference in percentage of patients reaching HbA1c below 7% will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2023
- Study start10 Jun 2023
- Primary completion31 Oct 2023
- Study completion31 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Giorgino, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
- Investigators
- Francesco Giorgino, PhD, Principal investigator, University of Bari Aldo Moro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06120556
- Sponsor's protocol ID
- AOUConsorziale
- Status last verified
- Jan 2024
- First submitted
- 27 Oct 2023
- Last updated
- 30 Jan 2024
- Results posted
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
Publications
Ahlqvist E, Storm P, Karajamaki A, Martinell M, Dorkhan M, Carlsson A, Vikman P, Prasad RB, Aly DM, Almgren P, Wessman Y, Shaat N, Spegel P, Mulder H, Lindholm E, Melander O, Hansson O, Malmqvist U, Lernmark A, Lahti K, Forsen T, Tuomi T, Rosengren AH, Groop L. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018 May;6(5):361-369. doi: 10.1016/S2213-8587(18)30051-2. Epub 2018 Mar 5.
PubMed 29503172Bello-Chavolla OY, Bahena-Lopez JP, Vargas-Vazquez A, Antonio-Villa NE, Marquez-Salinas A, Fermin-Martinez CA, Rojas R, Mehta R, Cruz-Bautista I, Hernandez-Jimenez S, Garcia-Ulloa AC, Almeda-Valdes P, Aguilar-Salinas CA; Metabolic Syndrome Study Group; Group of Study CAIPaDi. Clinical characterization of data-driven diabetes subgroups in Mexicans using a reproducible machine learning approach. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001550. doi: 10.1136/bmjdrc-2020-001550.
PubMed 32699108Dennis JM, Shields BM, Henley WE, Jones AG, Hattersley AT. Disease progression and treatment response in data-driven subgroups of type 2 diabetes compared with models based on simple clinical features: an analysis using clinical trial data. Lancet Diabetes Endocrinol. 2019 Jun;7(6):442-451. doi: 10.1016/S2213-8587(19)30087-7. Epub 2019 Apr 29.
PubMed 31047901
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Glucagon-like Peptide-1 Receptor Agonists According to Type 2 Diabetes Subtypes: an Italian Monocentric Retrospective Study
- ClinicalTrials.gov ID
- NCT06120556
- Acronym / sponsor ID
- AOUConsorziale
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- type 2 diabetes, GLP-1 receptor agonists, subtypes, phenotypes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Azienda Ospedaliero-Universitaria Consorziale Policlinico di BariUniversity, hospital or other
- Study start
- 10 Jun 2023 (actual)
- Primary completion
- 31 Oct 2023 (actual)
- Study completion
- 31 Oct 2023 (actual)
- First posted
- 7 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this observational retrospective study is to understand whether glucagon-like peptide-1 receptor agonists (GLP-1RA), which are a group of antidiabetes drugs, may act differently in different subtypes of patients with type 2 diabetes.
The main questions it aims to answer are:
- people with type 2 diabetes belonging to specific subtypes respond better (or worse) to GLP-1RA?
- the beneficial effect of GLP-1RA may last longer in people with type 2 diabetes belonging to specific subtypes?
- what are the clinical characteristics that better explain the efficacy and durability of GLP-1 receptor agonists in type 2 diabetes management?
Clinical data from records of patients attending the diabetes outpatient clinic of our facility will be retrieved to compare the outcomes of GLP-1 receptor agonists in patients belonging to four subtypes of type 2 diabetes.
Detailed description
Patients with type 2 diabetes are all characterized by hyperglycemia, however their probability to develop micro- and micro-vascular complications. A classification of adult-onset diabetes in 5 subtypes was recently proposed: severe autoimmune diabetes (SAID - including type 1 diabetes and latent autoimmune diabetes in adults LADA), severe insulin resistant diabetes (SIRD), severe insulin deficient diabetes (SIDD), mild age related diabetes (MARD), mild obesity-related diabetes (MOD). This classification has been validated in a multiple populations of patients with recent onset diabetes (within 5 years).
However, this classification requires the measurement of c-peptide/insulinemia or anti- glutamic acid decarboxylase (GAD) antibodies, limiting its applicability in everyday clinical practice. An alternative algorithm requiring easily available clinical characteristics, such as BMI, height, waist circumference, HbA1c, fasting blood glucose, lipid profile, age and age at diagnosis was recently introduced and validated.
In this retrospective observational study, the calculated sample size was of 128 patients, in 4 groups, with alpha 0.05, 1-beta 0.80, effect size 0.3.
The following data will be retrieved for eligible patients: age, sex, diabetes duration, age at diagnosis, antidiabetes therapy, body weight, height, waist circumference, fasting blood glucose, HbA1c, total and HDL and LDL cholesterol, triglycerides, creatinine, microalbuminuria. The algorithm available online (https://uiem.shinyapps.io/diabetes_clusters_app/), will be used to assign enrolled patients to the 4 subtypes of type 2 diabetes (SIDD, SIRD, MARD, MOD).
If available, information regarding micro- and macro-vascular complications of diabetes will be retrieved.
All data will be collected at baseline visit and every follow-up visit (the first follow-up visit should 6-12 months following prescription of a GLP-1 receptor agonist).
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Severe Insulin Resistant Diabetes (SIRD) | – | Drug: GLP-1 receptor agonistPatients with SIRD are characterized by high BMI and high insulin resistance and low HbA1c. These patients likely develop diabetic kidney disease. Defined according to the simplified algorithm proposed by Bello-Chavolla et al. requiring the following data: age at diabetes diagnosis, age, BMI, height, waist circumference, HbA1c, fasting blood glucose, fasting triglycerides, HDL cholesterol |
| Mild Age-Related Diabetes (MARD) | – | Drug: GLP-1 receptor agonistPatients with MARD are characterized by late onset diabetes without extreme features. Defined according to the simplified algorithm proposed by Bello-Chavolla et al. requiring the following data: age at diabetes diagnosis, age, BMI, height, waist circumference, HbA1c, fasting blood glucose, fasting triglycerides, HDL cholesterol |
| Mild Obesity-related Diabetes (MOD) | – | Drug: GLP-1 receptor agonistPatients with MOD are characterized by high BMI without insulin resistance. Defined according to the simplified algorithm proposed by Bello-Chavolla et al. requiring the following data: age at diabetes diagnosis, age, BMI, height, waist circumference, HbA1c, fasting blood glucose, fasting triglycerides, HDL cholesterol |
| Severe Insulin Deficient Diabetes (SIDD) | – | Drug: GLP-1 receptor agonistPatients with SIDD are characterized by high HbA1c and rapid progression to insulin therapy. These patients likely develop retinopathy, even in the first years after diagnosis. Defined according to the simplified algorithm proposed by Bello-Chavolla et al. requiring the following data: age at diabetes diagnosis, age, BMI, height, waist circumference, HbA1c, fasting blood glucose, fasting triglycerides, HDL cholesterol |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients who attended the Day Service for diabetes of the Endocrinology Unit of the University Hospital A.O.U. Policlinico di Bari, Puglia, Italy from January 1st 2012 to October 1st 2023 will be consecutively evaluated for inclusion.
Key inclusion criteria (5 listed)
- Italian patients with type 2 diabetes
- Onset of diabetes at ≥ 50 years
- Diagnosis of type 2 diabetes ≤ 5 years from enrollment
- BMI ≥ 25 kg/m2
- Patients receiving a GLP-1RA prescription for the first time with at least one follow-up visit at 6-12 months from first prescription
Key exclusion criteria (2 listed)
- Autoimmune diabetes, monogenic diabetes, secondary diabetes
- History of diabetic ketoacidosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GLP-1 receptor agonistPatients initiating a GLP-1 receptor agonist (i.e. liraglutide, dulaglutide, semaglutide) will be included in the study. | Drug | Mild Age-Related Diabetes (MARD), Mild Obesity-related Diabetes (MOD), Severe Insulin Deficient Diabetes (SIDD), Severe Insulin Resistant Diabetes (SIRD) |
Primary outcome
Difference in HbA1c change from baseline (%) among SIDD, SIRD, MARD, MOD subtypes
Time frame: Difference in HbA1c change from baseline will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
4 secondary outcomes
Difference in time to failure among SIDD, SIRD, MARD, MOD subtypes
Time frame: Difference in time to failure will be assessed up to the last available visit (up to 36 months)
Difference in fasting blood glucose change from baseline (mg/dl) among SIDD, SIRD, MARD, MOD subtypes
Time frame: Difference in fasting blood glucose change from baseline (mg/dl) will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Difference in body weight change from baseline (kg) among SIDD, SIRD, MARD, MOD subtypes
Time frame: Difference in body weight change from baseline (kg) will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Difference in percentage of patients reaching HbA1c below 7% among SIDD, SIRD, MARD, MOD subtypes
Time frame: Difference in percentage of patients reaching HbA1c below 7% will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
- Background: PubMed 29503172Ahlqvist E, Storm P, Karajamaki A, Martinell M, Dorkhan M, Carlsson A, Vikman P, Prasad RB, Aly DM, Almgren P, Wessman Y, Shaat N, Spegel P, Mulder H, Lindholm E, Melander O, Hansson O, Malmqvist U, Lernmark A, Lahti K, Forsen T, Tuomi T, Rosengren AH, Groop L. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018 May;6(5):361-369. doi: 10.1016/S2213-8587(18)30051-2. Epub 2018 Mar 5.
- Background: PubMed 32699108Bello-Chavolla OY, Bahena-Lopez JP, Vargas-Vazquez A, Antonio-Villa NE, Marquez-Salinas A, Fermin-Martinez CA, Rojas R, Mehta R, Cruz-Bautista I, Hernandez-Jimenez S, Garcia-Ulloa AC, Almeda-Valdes P, Aguilar-Salinas CA; Metabolic Syndrome Study Group; Group of Study CAIPaDi. Clinical characterization of data-driven diabetes subgroups in Mexicans using a reproducible machine learning approach. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001550. doi: 10.1136/bmjdrc-2020-001550.
- Background: PubMed 31047901Dennis JM, Shields BM, Henley WE, Jones AG, Hattersley AT. Disease progression and treatment response in data-driven subgroups of type 2 diabetes compared with models based on simple clinical features: an analysis using clinical trial data. Lancet Diabetes Endocrinol. 2019 Jun;7(6):442-451. doi: 10.1016/S2213-8587(19)30087-7. Epub 2019 Apr 29.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francesco Giorgino, PhD principal investigator
University of Bari Aldo Moro
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diabetes Mellitus, Type 2, run by Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in HbA1c change from baseline (%) among SIDD, SIRD, MARD, MOD subtypes (time frame: Difference in HbA1c change from baseline will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06120556, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2024.