Clinical trial NCT04034524: Cardiovascular Outcomes and HbA1c Among Patients With Type 2 Diabetes Newly Initiating GLP1RAs vs Basal Insulin
Official title: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2019-07-26
Enrollment: 20000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with type 2 diabetes with prior and concomitant use of metformin and other oral anti diabetic agents

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.

Eligibility criteria: 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%

Primary outcomes:
measure: Time until first composite CV event (myocardial infarction, stroke)
timeFrame: Through Study Completion, an estimated average of 1 year
Secondary outcomes:
measure: Time until first myocardial infarction
timeFrame: Through Study Completion, an estimated average of 1 year
measure: Time until first stroke
timeFrame: Through Study Completion, an estimated average of 1 year
measure: Time until first serious hypoglycemic event
timeFrame: Through Study Completion, an estimated average of 1 year
measure: Time until first episode of acute pancreatitis
timeFrame: Through Study Completion, an estimated average of 1 year
measure: Time until first episode of acute cholecystitis
timeFrame: Through Study Completion, an estimated average of 1 year
Other outcomes:
measure: Proportion of patients with HbA1c post-index < 7% (EAGLE)
timeFrame: 24 weeks
measure: Proportion of patients with HbA1c post-index < 8% (EAGLE)
timeFrame: 24 weeks
measure: Change from baseline HbA1c
timeFrame: 24 weeks
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Jessica M Franklin, PHD
role: STUDY_CHAIR
References: