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

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT04034524
• Collaborator: (none)
• Enrollment: 20,000
• Location: 1
• Anticipated Duration (Months): 20
• Patients Per Site Per Month: 998

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	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 Design

• Study Type: Observational
• Anticipated Enrollment: 20000 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• 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
• Actual Study Start Date: May 1, 2019
• Anticipated Primary Completion Date: Dec 31, 2020
• Anticipated Study Completion Date: Dec 31, 2020

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. Time until first composite CV event (myocardial infarction, stroke) [Through Study Completion, an estimated average of 1 year]

Secondary Outcome Measures

1. Time until first myocardial infarction [Through Study Completion, an estimated average of 1 year]

2. Time until first stroke [Through Study Completion, an estimated average of 1 year]

3. Time until first serious hypoglycemic event [Through Study Completion, an estimated average of 1 year]

4. Time until first episode of acute pancreatitis [Through Study Completion, an estimated average of 1 year]

5. Time until first episode of acute cholecystitis [Through Study Completion, an estimated average of 1 year]

Other Outcome Measures

1. Proportion of patients with HbA1c post-index < 7% (EAGLE) [24 weeks]

2. Proportion of patients with HbA1c post-index < 8% (EAGLE) [24 weeks]

3. Change from baseline HbA1c [24 weeks]

   Weighted mean

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All

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%

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02138

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jing Luo, Instructor of Medicine, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT04034524
• Other Study ID Numbers: 2011P002580-118
• First Posted: Jul 26, 2019
• Last Update Posted: Jul 9, 2020
• Last Verified: Jul 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc

Study Results

No Results Posted as of Jul 9, 2020