title: Delays in treatment intensification with oral antidiabetic drugs and risk of microvascular and macrovascular events in patients with poor glycaemic control: An individual patient simulation study.
abstract: To use the Archimedes model to estimate the consequences of delays in oral antidiabetic drug (OAD) treatment intensification on glycaemic control and long-term outcomes at 5 and 20 years.
  
  
  
  Using real-world data, we modelled a cohort of hypothetical patients with glycated haemoglobin (HbA1c) ≥8%, on metformin, with no history of insulin use. The cohort included 3 strata based on the number of OADs taken at baseline. The first add-on in the intensification sequence was a sulphonylurea, next was a dipeptidyl peptidase-4 inhibitor, and last, a thiazolidinedione. The scenarios included either no delay or delay, based on observed and extrapolated times to intensification.
  
  
  
  At 1 year, HbA1c was 6.8% for patients intensifying without delay, and 8.2% for those delaying intensification. For no delay vs delay, risks of major adverse cardiac events, myocardial infarction, heart failure and amputations were reduced by 18.0%, 25.0%, 13.7%, and 20.4%, respectively, at 5 years; severe hypoglycaemia risk, however, increased to 19% for the no delay scenario vs 12.5% for delay. At 20 years, the results showed similar trends to those at 5 years.
  
  
  
  Timing of intensification of OAD therapy according to guideline recommendations led to greater reductions in HbA1c and lower risks of complications, but higher risks of hypoglycaemia than delaying intensification. These results highlight the potential impact of timely treatment intensification on long-term outcomes.
authors.affiliation: Evidera, San Francisco, California.
authors.forename: Henry J
authors.identifier: 0000-0001-6077-492X
authors.initials: HJ
authors.lastname: Folse
authors.affiliation: Bristol-Myers Squibb, Wallingford, Connecticut.
authors.forename: Jayanti
authors.initials: J
authors.lastname: Mukherjee
authors.affiliation: AstraZeneca Pharmaceuticals, Fort Washington, Pennsylvania.
authors.forename: John J
authors.initials: JJ
authors.lastname: Sheehan
authors.affiliation: Evidera, Lexington, Massachusetts.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Ward
authors.affiliation: Evidera, San Francisco, California.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Pelkey
authors.affiliation: Evidera, San Francisco, California.
authors.forename: Tuan A
authors.initials: TA
authors.lastname: Dinh
authors.affiliation: AstraZeneca, One MedImmune Way, Gaithersburg, Maryland.
authors.forename: Lei
authors.initials: L
authors.lastname: Qin
authors.affiliation: AstraZeneca, One MedImmune Way, Gaithersburg, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D016903:Drug Monitoring; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D016544:Patient Simulation; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D061665:Time-to-Treatment
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C517652:hemoglobin A1c protein, human
keywords: DPP-4 inhibitor; antidiabetic drug; macrovascular disease; sulphonylureas; thiazolidinediones