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
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Brigham and Women's Hospital
- Enrollment
- 20,000
- Locations
- 1
- Primary Endpoint
- Time until first composite CV event (myocardial infarction, stroke)
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Retrospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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%
Arms & Interventions
New users of GLP1 receptor agonists (exposure)
Intervention: GLP-1 receptor agonist (Drug)
New users of basal insulin (reference)
Intervention: Insulin (Drug)
Outcomes
Primary Outcomes
Time until first composite CV event (myocardial infarction, stroke)
Time Frame: Through Study Completion, an estimated average of 1 year
Secondary Outcomes
- Time until first myocardial infarction(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 stroke(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)
Investigators
Jing Luo
Instructor of Medicine
Brigham and Women's Hospital