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Efficacy of Glucagon-like Peptide-1 Receptor Agonists According to Type 2 Diabetes Subtypes

Completed
Conditions
Diabetes Mellitus, Type 2
Interventions
Drug: GLP-1 receptor agonist
Registration Number
NCT06120556
Lead Sponsor
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
Brief 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.

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
130
Inclusion Criteria
  • 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
Exclusion Criteria
  • Autoimmune diabetes, monogenic diabetes, secondary diabetes
  • History of diabetic ketoacidosis

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Severe Insulin Resistant Diabetes (SIRD)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)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)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)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
Primary Outcome Measures
NameTimeMethod
Difference in HbA1c change from baseline (%) among SIDD, SIRD, MARD, MOD subtypesDifference in HbA1c change from baseline will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Secondary Outcome Measures
NameTimeMethod
Difference in body weight change from baseline (kg) among SIDD, SIRD, MARD, MOD subtypesDifference in body weight change from baseline (kg) will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)

kg

Difference in percentage of patients reaching HbA1c below 7% among SIDD, SIRD, MARD, MOD subtypesDifference in percentage of patients reaching HbA1c below 7% will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Difference in time to failure among SIDD, SIRD, MARD, MOD subtypesDifference in time to failure will be assessed up to the last available visit (up to 36 months)

In patients reaching HbA1c \<7% at first follow-up visit, the difference in time to failure (defined as HbA1c equal or above 7%)

Difference in fasting blood glucose change from baseline (mg/dl) among SIDD, SIRD, MARD, MOD subtypesDifference 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)

mg/dl

Trial Locations

Locations (1)

Azienda Ospedaliero-Universitaria Policlinico Bari

🇮🇹

Bari, Italy

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