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

Conditions
Diabetes Mellitus, Type 2
Interventions
Drug: GLP-1 receptor agonist
Registration Number
NCT04034524
Lead Sponsor
Brigham and Women's Hospital
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
20000
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%

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
New users of GLP1 receptor agonists (exposure)GLP-1 receptor agonist-
New users of basal insulin (reference)Insulin-
Primary Outcome Measures
NameTimeMethod
Time until first composite CV event (myocardial infarction, stroke)Through Study Completion, an estimated average of 1 year
Secondary Outcome Measures
NameTimeMethod
Time until first myocardial infarctionThrough Study Completion, an estimated average of 1 year
Time until first serious hypoglycemic eventThrough Study Completion, an estimated average of 1 year
Time until first strokeThrough Study Completion, an estimated average of 1 year
Time until first episode of acute pancreatitisThrough Study Completion, an estimated average of 1 year
Time until first episode of acute cholecystitisThrough Study Completion, an estimated average of 1 year

Trial Locations

Locations (1)

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

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