title: Cardiovascular outcomes associated with a new once-weekly GLP-1 receptor agonist vs. traditional therapies for type 2 diabetes: a simulation analysis.
abstract: OBJECTIVE
  The effect of glucose-lowering agents on diabetes-related complications including cardiovascular (CV) events is of major importance. In the absence of a long-term study, we simulated such a trial using a mathematical model where subjects were given exenatide once-weekly (EQW), which has been shown to improve glycaemic control and reduce weight, systolic blood pressure (SBP) and lipids in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Using the Archimedes Model, we followed a simulated population derived from individuals with T2DM in NHANES who were drug-naïve or on oral agents only. We modelled the effects of four treatment strategies including standard care (SC, maintaining levels of control seen in NHANES), intensive glycaemic control (IGC, target HbA1c < 7% with conventional antidiabetic agents) and two versions of EQW added to SC: one with glycaemic and weight reduction only (EQW-1) and one with additional improvements in SBP and lipids (EQW-2). EQW strategies were derived from 52-week clinical trial data. Endpoints included macrovascular and microvascular outcomes.
  
  
  RESULTS
  Simulated EQW treatment resulted in earlier benefit and 2-3 times greater relative reductions in major adverse CV events than IGC when compared to SC (6% relative reduction by year 20 for IGC vs. 12 and 17% for the EQW strategies). For microvascular complications, EQW showed comparable benefit to IGC for neuropathy but significantly greater impact on renal complications.
  
  
  CONCLUSIONS
  This analysis shows that the novel drug EQW has the potential to greatly reduce CV events through its combined effects on glycaemia, weight and other CV risk factors.
authors.affiliation: Archimedes Inc., San Francisco, CA, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Peskin
authors.forename: A V
authors.initials: AV
authors.lastname: Shcheprov
authors.forename: K S
authors.initials: KS
authors.lastname: Boye
authors.forename: S
authors.initials: S
authors.lastname: Bruce
authors.forename: D G
authors.initials: DG
authors.lastname: Maggs
authors.forename: J A
authors.initials: JA
authors.lastname: Gaebler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000517:prevention & control; D004334:Drug Administration Schedule; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D018027:Receptors, Glucagon / Q000819:agonists*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D018027:Receptors, Glucagon; C000593833:GLP1R protein, human