title: Real-World Glycemic Control from GLP-1RA Therapy with and Without Concurrent Insulin in Patients with Type 2 Diabetes.
abstract: BACKGROUND
  Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are recommended as add-on therapy in patients with uncontrolled type 2 diabetes (T2D), with no specific guidance as to timing versus insulin. Furthermore, real-world data assessing GLP-1RA outcomes with or without concurrent insulin therapy are lacking.
  
  
  OBJECTIVE
  To identify glycemic response with GLP-1RAs by insulin use in patients with T2D at 1-year follow-up to inform decisions regarding GLP-1RA use with or without insulin.
  
  
  METHODS
  This uncontrolled retrospective cohort study included adults with T2D in the Quintiles Electronic Medical Records Database who were newly prescribed GLP-1RA therapy with exenatide once weekly or liraglutide once daily between February 1, 2012, and March 31, 2013 (index period). Primary outcomes were change in hemoglobin A1c (A1c) at 1 year and attainment of A1c < 7%, < 8%, and < 9%. Results were stratified by baseline insulin use, which was defined as no insulin use at baseline, insulin initiated with a GLP-1RA on index date, and insulin prescribed before starting GLP-1RA therapy. Secondary outcomes included 1-year weight, low-density lipoprotein cholesterol (LDL-C), and blood pressure outcomes for the study population. Adjusted mean (marginal) change in A1c at 1 year was estimated using multivariate linear regression, and multivariate logistic regression was used to estimate the likelihood of patients attaining A1c < 7% at follow-up, controlling for potential confounders.
  
  
  RESULTS
  This study included 5,141 patients with a mean (SD) age of 57.0 (10.9) years, 53.5% of whom were females, and with a mean baseline A1c of 8.4% (1.6). Overall, 35.4% had no baseline insulin use, 42.9% were prescribed insulin before starting GLP-1RA therapy, and 21.7% were started on insulin with a GLP-1RA. The adjusted mean A1c reduction at 1 year was 0.75% (95% CI = -0.86 to -0.63) for patients initiating insulin on index date, 0.61% (95% CI = -0.70 to -0.51) for patients with no baseline insulin use, and 0.23% (95% CI = -0.33 to -0.13) for patients prescribed insulin before GLP-1RA therapy. Patients with no baseline insulin or who coinitiated insulin and a GLP-1RA were more likely to attain A1c < 7% at follow-up versus patients prescribed insulin before initiating GLP-1RA therapy (OR = 1.50, 95% CI = 1.08 to 2.09 and OR = 1.85, 95% CI = 1.30 to 2.62, respectively). At 1-year follow-up, significant improvements in weight, LDL-C, and blood pressures were also observed.
  
  
  CONCLUSIONS
  GLP-1RA therapy was associated with significant improvements in glycemic control when used with or without insulin, as well as reductions in weight and LDL-C overall. However, greater A1c reductions and a higher likelihood of attaining A1c goal levels were observed when a GLP-1RA was initiated alone or with insulin than when a GLP-1RA was added to a regimen that included insulin. GLP-1RA therapy is an effective treatment option when used with or without insulin and may be considered in patients with uncontrolled glycemia.
  
  
  BACKGROUND
  The study was funded by a collaborative research grant from AstraZeneca. Employees of AstraZeneca participated in most aspects of the study and in manuscript preparation. Nguyen and Hurd are employed by, and hold stock in, AstraZeneca. McAdam-Marx reports participation in the AMCP Diabetes Partnership and has stock ownership in GlaxoSmithKline. Study concept and design were contributed by Nguyen, McAdam-Marx, and Singhal, along with Unni and Schauerhamer. Singhal, Unni, Nguyen, and McAdam-Marx collected the data, with assistance from Schauerhamer and Hurd, and data interpretation was performed by Unni, Hurd, McAdam-Marx, Singhal, Nguyen, and Schauerhamer. The manuscript was written by Singhal, Schauerhamer, Unni, and McAdam-Marx, along with Nguyen and Hurd, and revised by McAdam-Marx, Singhal, Unni, and Nguyen, along with Schauerhamer and Hurd.
authors.affiliation: 1 Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, University of Utah, Salt Lake City.
authors.forename: Mukul
authors.initials: M
authors.lastname: Singhal
authors.affiliation: 2 Pharmacotherapy Outcomes Research Center, University of Utah, Salt Lake City.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Unni
authors.affiliation: 1 Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, University of Utah, Salt Lake City.
authors.forename: Marisa
authors.initials: M
authors.lastname: Schauerhamer
authors.affiliation: 3 AstraZeneca, Fort Washington, Pennsylvania.
authors.forename: Hiep
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: 3 AstraZeneca, Fort Washington, Pennsylvania.
authors.forename: Jeff
authors.initials: J
authors.lastname: Hurd
authors.affiliation: 1 Department of Pharmacotherapy and Pharmacotherapy Outcomes Research Center, University of Utah, Salt Lake City.
authors.forename: Carrie
authors.initials: C
authors.lastname: McAdam-Marx
mesh_terms: D001786:Blood Glucose / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000378:metabolism; D000069450:Liraglutide / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000627:therapeutic use; D012189:Retrospective Studies; D014688:Venoms / Q000627:therapeutic use; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008077:Lipoproteins, LDL; D000069450:Liraglutide; D010455:Peptides; D014688:Venoms; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C000593833:GLP1R protein, human