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

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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: GLP-1 receptor agonist; Drug: 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 Type: Observational
• Enrollment (Anticipated): 20000

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02138
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with HbA1c post-index < 7% (EAGLE)		24 weeks
Proportion of patients with HbA1c post-index < 8% (EAGLE)		24 weeks
Change from baseline HbA1c	Weighted mean	24 weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Study Chair: Jessica M Franklin, PHD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: July 24, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 26, 2019

Study Record Updates

• Last Update Posted (Actual): July 9, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 2011P002580-118

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No