Real-world Evaluation of GLP-1 Receptor Agonists (GLP-1RA) on Efficacy and Persistence, Adherence and Therapeutic Inertia Among Type 2 Diabetes Adults With Obesity

Study Overview
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Brief Summary
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Type 2 diabetes (T2D) is a progressive chronic condition associated with a high morbi-mortality that has a considerable impact on healthcare resources. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are incretin mimetics that have been shown to improve glycemic control with a low associated risk of hypoglycemia. Additionally, previous studies have linked the use of GLP-1RA with a reduction in the risk of cardiovascular events and kidney disease progression. Despite these positive results, GLP1-RA´s prescription, following the failure of treatment with metformin monotherapy or dual therapy, remains low in Spain compared to other countries in our milieu. Furthermore, the use of this therapeutic class is not homogeneous across the different autonomous communities in Spain, and, no objective justification for these differences seems to exist. Consequently, there is a need to understand which are the benefits associated with the use of GLP-1RA, versus intensification with other oral agents, in real-life conditions. In this study, the impact of the use of GLP-1RA on clinical outcomes such as all-cause mortality, cardiovascular and renal outcomes as well as severe hypoglycemia will be evaluated based on the analysis of longitudinal databases that collect the variables of interest generated in a real-life scenario. In addition, both persistence and adherence to treatment in patients treated with GLP-1RA and its impact on the clinical outcomes of interest will be studied. Finally, therapeutic inertia will be analyzed. All these data will contribute to generating cost-effective strategies aimed at improving health outcomes among T2D patients in our setting, reinforcing persistence and adherence to the prescribed treatment, and reducing therapeutic inertia in this group of patients. Since the use of GLP-1RA versus intensification with other oral agents has been associated with better glycemic control, and, when compared to intensification with basal insulin, with a lower incidence of severe hypoglycemia, we hypothesized that T2D adults treated with GLP-1RA would present a lower incidence of cardiovascular and renal outcomes and fewer hospitalizations due to severe hypoglycemia events as well as a decreased all-cause mortality. On the other hand, patients on GLP-1RA who would present greater persistence and adherence to treatment should experience fewer cardiovascular and renal outcomes and lower mortality compared to those with less persistence and adherence. Finally, it is possible that the type of GLP-1RA and the mode of administration, weekly versus daily, may influence adherence, persistence and therapeutic inertia in this group of patients.

Official Title
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Real-world Evaluation of GLP-1 Receptor Agonists (GLP-1RA) on Efficacy and Persistence, Adherence and Therapeutic Inertia Among Type 2 Diabetes Adults With Obesity in the Department of Health of Valencia Clínico-Malvarrosa

Conditions
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Type 2 Diabetes, Obesity

Intervention / Treatment
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* Drug: GLP-1RA
* Drug: SGLT2i
* Drug: Insulin
* Drug: Miscellany


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with type 2 diabetes Individuals with at least a 6-month prescription Exclusion Criteria: Individuals below 18 Individuals with less than a 6-month prescription

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 125 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GLP-1RA<br>All GLP-1RA users: all T2D adults treated with GLP-1RA or initiating a GLP-1RA during the study period | Drug: GLP-1RA<br>* All T2D adults treated with Glucagon-like peptide-1 receptor agonists (GLP-1RA) or initiating a GLP-1RA during the study period<br>|
| SGLT2i<br>SGLT2 inhibitors users with no GLP-1RA prescription: all T2D adults treated with SGLT2i or initiating treatment with SGLT2i during the study period and who were not treated with a GLP-1RA | Drug: SGLT2i<br>* SGLT2 inhibitors users with no GLP-1RA prescription: all T2D adults treated with Sodium/glucose cotransporter-2 inhibitors (SGLT2i) or initiating treatment with SGLT2i during the study period and who were not treated with a GLP-1RA<br>|
| Insulin<br>Insulin users with no GLP-1RA and/or SGLT2i prescriptions: all T2D adults treated with insulin or initiating insulin treatment during the study period and who were not treated with GLP-1RA/SGLT2i | Drug: Insulin<br>* Insulin users with no GLP-1RA and/or SGLT2i prescriptions: all T2D adults treated with insulin or initiating insulin treatment during the study period and who were not treated with GLP-1RA/SGLT2i<br>|
| Miscellany<br>Other glucose-lowering agents users: all T2D adults who were not treated with GLP-1RA and/or SGLT2i and/or insulin during the study period. | Drug: Miscellany<br>* Other glucose-lowering agents users: all T2D adults who were not treated with GLP-1RA and/or SGLT2i and/or insulin during the study period and who were treated with other glucose-lowering agents during the study period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major acute cardiovascular events | In this work, this composite includes patients suffering from non-fatal acute myocardial infarction (AMI) and non-fatal stroke, transient ischemic attack (TIA), all-cause death, and, heart failure events occurring during the study period (from inclusion in the study until the event or the end of the study period, whichever came first). | From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major acute cardiovascular events without heart failure | In this work, this composite includes patients suffering from non-fatal acute myocardial infarction (AMI) and non-fatal stroke, transient ischemic attack (TIA) and all-cause death occurring during the study period (from inclusion in the study until the event or the end of the study period, whichever came first). | From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first. | 
| AMI | Acute myocardial infarction events occurring during the study follow-up (from inclusion in the study until the event or the end of the study period, whichever came first. | From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first. | 
| Stroke | Stroke events occurring during the study follow-up (from inclusion in the study until the event or the end of the study period, whichever came first. | From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first. | 
| Heart Failure | Heart failure hospitalization occurring during the study follow-up (from inclusion in the study until the event or the end of the study period, whichever came first. | Through study completion (from inclusion in the study until the event or the end of the study period, whichever came first) | 
| all-cause death | Death from all causes occurring during the study follow-up (from inclusion in the study until the event or the end of the study period, whichever came first. | From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first. | 
| Renal progression | Sustained 40% reduction in eGFR occurring during the study follow-up (from inclusion in the study until the event or the end of the study period, whichever came first. | From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first. | 
| atrial fibrillation | Events of atrial fibrillation episodes occurring during the study follow-up (from inclusion in the study until the event or the end of the study period, whichever came first. | From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first. | 
| Hypoglycemia | Severe hypoglycemia requiring hospitalization occurring during the study follow-up (from inclusion in the study until the event or the end of the study period, whichever came first. | From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first. | 
| Persistence | Persistence on treatment was defined as the percentage of patients continuing treatment from the start of the study period or since the first prescription during the study period until evidence of discontinuation or the end of the study period. | From inclusion in the study, starting from 01/01/2014, until the end of the study, on 31/12/2019. | 
| Adherence | Treatment adherence was defined as the proportion of days covered (days in which an individual had access to the medication) from the start of the study period or since the first prescription during the study period until treatment discontinuation | From inclusion in the study, starting from 01/01/2014, until the end of the study, on 31/12/2019. | 
| Therapeutic inertia | Therapeutic inertia was defined as non-intensification of treatment once started despite HbA1c ≥7.5% during follow-up. | From inclusion in the study, starting from 01/01/2014, until the end of the study, on 31/12/2019. |