Cardiovascular Outcomes and HbA1c Among Patients With Type 2 Diabetes Newly Initiating GLP1RAs vs Basal Insulin

Study Overview
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Brief Summary
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This study will compare hemoglobin a1c (HbA1c) and cardiovascular (CV) outcomes among patients with type 2 diabetes newly initiating a GLP1-receptor agonist or basal insulin.

Detailed Description
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The 2019 ADA-EASD clinical treatment guidelines recommend a GLP-1RA over basal insulin for patients with type 2 diabetes with suboptimal glycemic control despite metformin and a second-line glucose lowering agent. The basis of this recommendation is due to the side effect profiles of these two medications (i.e. reduced risk of hypoglycemia, some weight loss with GLP-1RA), convenience (once weekly injection) and the fact that the price of insulin has skyrocketed in recent years. Prior head-to-head randomized trials (EAGLE, LEAD 5) comparing select GLP-1RA and basal insulin have found mixed results. In EAGLE, adding either insulin glargine or liraglutide to patients with poorly controlled type 2 diabetes found no differences in the primary outcome (percentage of people reaching HbA1c < 7%). In LEAD 5, liraglutide was associated with a slightly greater HbA1c reduction than glargine, however the dose of insulin was approximately 50% less than the dose used in EAGLE. The objective of this observational study is to describe the comparative effectiveness and safety of newly initiating a GLP1RA versus basal insulin in patients with type 2 diabetes using metformin and another oral glucose lowering medicine.

Official Title
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An Observational Study of Glycemic Control and Cardiovascular Outcomes Among Patients With Type 2 Diabetes Newly Initiating Glucagon-like Peptide-1 Receptor Agonists (GLP1) Versus Basal Insulin in Routine Care Settings

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: GLP-1 receptor agonist
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age>=18 years at least 180 days of continuous enrollment prior to index date at least 1 Type 2 diabetes diagnosis code prior to index date (for cohort #1) at least 2 metformin dispensings prior to index date AND days supply overlap on cohort entry date (with 14 days of grace period before) Exclusion Criteria: any type 1 diabetes diagnosis code prior to index date medullary thyroid carcinoma, multiple endocrine neoplasia type 2 (both black box warnings) prior to index date h/o pancreatitis h/o recurrent hypoglycemia (i.e. more than 1 hospitalization / emergency department encounter in primary diagnosis position for hypoglycemia) index injectable is a combination of GLP1-RA plus insulin index GLP1-RA is Saxenda (indicated for weight loss) or liraglutide at 3.0mg dose index insulin regimen includes both basal and prandial insulin, or premixed insulin Any prior GLP1-RA use (Applied washout for 180 days) Any prior insulin use; Sometimes insulin is transiently used at diagnosis (Applied washout for 180 days) Secondary diabetes Gestational diabetes Nursing home admission (because we don't have pharmacy claims) Age <18 years Chronic kidney disease stage 4-6 Advanced cancer End stage renal disease For A1c cohort only: -HbA1c >12%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| New users of GLP1 receptor agonists (exposure)<br> | Drug: GLP-1 receptor agonist<br>* any GLP-1 receptor agonist (other than Saxenda or liraglutide 3.0mg)<br>|
| New users of basal insulin (reference)<br> | Drug: Insulin<br>* glargine, detemir, neutral protamine Hagedorn (NPH), degludec<br>* Other names: Basal Insulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time until first composite CV event (myocardial infarction, stroke) |  | Through Study Completion, an estimated average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time until first myocardial infarction |  | Through Study Completion, an estimated average of 1 year | 
| Time until first stroke |  | Through Study Completion, an estimated average of 1 year | 
| Time until first serious hypoglycemic event |  | Through Study Completion, an estimated average of 1 year | 
| Time until first episode of acute pancreatitis |  | Through Study Completion, an estimated average of 1 year | 
| Time until first episode of acute cholecystitis |  | Through Study Completion, an estimated average of 1 year |