Descriptive Analysis of Long- and Intermediate-Acting Insulin in Adult Diabetics

Over the past 40 years, new types of insulins have been marketed to mirror the effect of endogenous insulin. With the existing long-acting insulin product patents expiring and the FDA approval of new biosimilar and innovator insulins, adults with diabetes and their physicians will have additional therapeutic options. This observational study will describe the patient characteristics of new and existing users of long-acting or intermediate acting insulins with and without oral anti-diabetic agents (OAD) as well as acute hypoglycemic episodes, acute cardiac events, and A1C measures. The Biologic and Biosimilars Collective Intelligence Consortium (BBCIC) will use the findings from this descriptive analysis to design a comparative study evaluating the real-world effectiveness and safety of biosimilar and innovator insulins.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: Long- and intermediate- acting insulins

Detailed Description

Additional information:

This protocol was designed as a descriptive analysis, not to support a hypothesis. This information is being provided to the public in the interest of transparency and for demonstrating the BBCIC's Distributed Research Network's (DRN) ability to define exposures, outcomes, covariates and confounders. When published, the report will caution that the protocol does not support any ability to compare safety or effectiveness but instead is to be used only to explore the feasibility of future, more detailed comparative analyses and to better understand the capabilities of the BBCIC project. Further, the report will caution that information from this protocol should not affect use of the medical products described in any way and the fact that the BBCIC is performing this descriptive analysis in no way suggests there is a safety or effectiveness issue with any of the products described.

• Study Type: Observational
• Enrollment (Actual): 103951

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Study subjects are selected according to inclusion criteria from a source population within the Sentinel Common Data Mode v5.0.1 (SCDM). The SCDM includes over 100 million individuals with 358 million person-years of observation time who are covered by Aetna, Anthem, Group Health Cooperative, Harvard Pilgrim Health Care, and HealthPartners. The time period assessed will be 1/1/2011 - 9/30/2015.

Description

Inclusion Criteria:

• Individuals with baseline period of 183 days with continuous medical and pharmacy coverage preceding the first prescription fill

• new and current users of the following exposures

  • Long-acting insulin (insulin detemir, glargine) alone or with metformin (LAI)
  • Long-acting insulin (insulin detemir, glargine) plus rapid/short acting insulin (with or without metformin) (LAI+R)
  • Long-acting insulin (insulin detemir, glargine) plus second-generation sulfonylurea agent (Glimepiride, Glipizide, Glipizide/Metformin, Glyburide, Glyburide/Metformin) (with or without metformin) (LAI+sulfa)
  • NPH insulin (Humulin, Novolin) alone or with metformin (NPH)
  • NPH insulin (Humulin, Novolin) plus rapid/short acting insulin (with or without metformin) (NHP+R)
  • NPH insulin (Humulin, Novolin) plus second-generation sulfonylurea agent (Glimepiride, Glipizide, Glipizide/Metformin, Glyburide, Glyburide/Metformin (with or without metformin) (NPH + sulfa)

Exclusion Criteria:

• Adult patients with diabetes with health insurance evidence of insulin pumps and/ or insulin pump supplies, gestational diabetes, liver disorders, dialysis, end-stage renal disease (ESRD), amputations, hemoglobinopathy, hemolytic anemia, or sickle cell anemia or transfusion
• Emergency Department (ED) visit for hypoglycemia; hospitalization or ED visit for cardiovascular event (stroke, acute myocardial infarction, unstable angina or diagnosis consistent with unstable angina -- i.e., occlusion without infarction or coronary insufficiency).
• Adult patients with diabetes on any other insulins except cohort insulins (i.e., rapid/short unless in combinations above).*

• Adult patients with diabetes on first-generation sulfonylureas, Dipeptidyl peptidase-4 (DPP4), Glucagon-like Peptide (GLP), Sodium-glucose cotransporter-2 (SGLT-2) or Thiazolidinediones (TZD) agents, alone or in combination with cohort defining drugs*:

  • First generation sulfonylurea agents (chlorpropamide, tolazamide )
  • TZDs (pioglitazone, pioglitazone/metformin, rosiglitazone, rosiglitazone/metformin
  • DPP4s (sitagliptin, saxagliptin, linagliptin, alogliptin)
  • GLP1 (exenatide, liraglutide, dulaglutide)
  • SGLT-2 (empagliflozin, canagliflozin, dapagliflozin)

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
Diabetes Type 1; Individuals diagnosed with type 1 diabetes exposed to Long- and intermediate- acting insulins	Drug: Long- and intermediate- acting insulins; alone or in combination with metformin, short-acting insulin, or second-generation sulfonylurea; Other Names: NPH, Lantus, Levemir, Toujeo
Diabetes Type 2; Individuals diagnosed with type 2 diabetes exposed to Long- and intermediate- acting insulins	Drug: Long- and intermediate- acting insulins; alone or in combination with metformin, short-acting insulin, or second-generation sulfonylurea; Other Names: NPH, Lantus, Levemir, Toujeo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serious hypoglycemic events	Incidence of serious hypoglycemic events in adult patient with diabetes population who use long- or intermediate-acting insulin	Anticipated completion January 2017

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious cardiac events	Incidence of serious cardiac events in adult patient with diabetes population who use long- or intermediate-acting insulin	Anticipated completion January 2017

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
A1C control	A1C control in adult patient with diabetes population who use long- or intermediate-acting insulin	Anticipated completion January 2017

Collaborators and Investigators

• Sponsor: Biologics & Biosimilars Collective Intelligence Consortium
• Collaborators: Merck Sharp & Dohme LLC; Pfizer; AbbVie; University of Pittsburgh; Boehringer Ingelheim; Kaiser Permanente; Amgen; Aetna, Inc.; Harvard Pilgrim Health Care; HealthCore, Inc.; University of Alabama; Rheumatologist and Healthcare Research; Momenta Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Dan Kent, PharmD,CDE, Kaiser Permanente; Principal Investigator: Cheryl Walraven, PhD, Aetna, Inc.

Publications and helpful links

General Publications

• Kent DJ, McMahill-Walraven CN, Panozzo CA, Pawloski PA, Haynes K, Marshall J, Brown J, Eichelberger B, Lockhart CM. Descriptive Analysis of Long- and Intermediate-Acting Insulin and Key Safety Outcomes in Adults with Type 2 Diabetes Mellitus. J Manag Care Spec Pharm. 2019 Nov;25(11):1162-1171. doi: 10.18553/jmcp.2019.19042. Epub 2019 Aug 12.
• McMahill-Walraven CN, Kent DJ, Panozzo CA, Pawloski PA, Haynes K, Marshall J, Brown J, Eichelberger B, Lockhart CM. Harnessing the Biologics and Biosimilars Collective Intelligence Consortium to Evaluate Patterns of Care. J Manag Care Spec Pharm. 2019 Nov;25(11):1156-1161. doi: 10.18553/jmcp.2019.19041. Epub 2019 Aug 9.

Helpful Links

• The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) was established in 2015 to address anticipated needs for post-marketed evidence generation for novel biologics, their corresponding biosimilars and other related products.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): September 30, 2015
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: September 28, 2016
• First Submitted That Met QC Criteria: October 3, 2016
• First Posted (Estimate): October 4, 2016

Study Record Updates

• Last Update Posted (Actual): July 30, 2021
• Last Update Submitted That Met QC Criteria: July 24, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Biologic and Biosimilars Collective Intelligence Consortium; BBCIC; Descriptive analysis
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin Detemir
• Other Study ID Numbers: BBCIC Insulins

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: BBCIC Charter requires transparency and publication
• IPD Sharing Supporting Information Type: Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No