title: AUTONOMY: the first randomized trial comparing two patient-driven approaches to initiate and titrate prandial insulin lispro in type 2 diabetes.
abstract: OBJECTIVE
  To compare two self-titration algorithms for initiating and escalating prandial insulin lispro in patients with type 2 diabetes inadequately controlled on basal insulin.
  
  
  METHODS
  The trial was designed as two independent, multinational, parallel, open-label studies (A and B), identical in design, to provide substantial evidence of efficacy and safety in endocrine and generalist settings. Subjects were 18-85 years old (study A: N = 528; study B: N = 578), on basal insulin plus oral antidiabetic drugs for ≥3 months, and had an HbA1c 7.0% to ≤12.0% (>53.0 to ≤107.7 mmol/mol). Once optimized on insulin glargine, subjects were randomized to one of two self-titration algorithm groups adjusting lispro either every day (Q1D) or every 3 days (Q3D) for 24 weeks. The primary outcome was the change in HbA1c from baseline. The primary and secondary objectives were evaluated for the overall population and subjects ≥65 years old.
  
  
  RESULTS
  Baseline HbA1c was similar (study A: Q1D 8.3% [67.2 mmol/mol] vs. Q3D 8.4% [68.3 mmol/mol], P = 0.453; study B: Q1D 8.3% [67.2 mmol/mol] vs. Q3D 8.4% [68.3 mmol/mol], P = 0.162). Both algorithms had significant and equivalent reductions in HbA1c from baseline (study A: Q3D -0.96% [-10.49 mmol/mol], Q1D -1.00% [-10.93 mmol/mol], Q3D-Q1D 0.04% [0.44 mmol/mol] [95% CI -0.15 to 0.22 (-1.64 to 2.40)]; study B: Q3D -0.92% [-10.06 mmol/mol], Q1D -0.98% [-10.71 mmol/mol], Q3D-Q1D 0.06% [0.66 mmol/mol] [95% CI -0.12 to 0.24 (-1.31 to 2.62)]). The incidence and rate of hypoglycemia were similar for Q3D and Q1D in both studies. In general, no clinically relevant differences were found between the two algorithms in subjects ≥65 years old in either study.
  
  
  CONCLUSIONS
  Prandial insulin lispro can effectively and safely be initiated, by either of two self-titrated algorithms, in a variety of practice settings.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA sedelman@ucsd.edu.
authors.forename: Steve V
authors.initials: SV
authors.lastname: Edelman
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Jennal
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Eli Lilly and Company, Indianapolis, IN.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Glass
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000069036:Insulin Glargine; D061268:Insulin Lispro / Q000008:administration & dosage* / Q000009:adverse effects; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D061268:Insulin Lispro; D049528:Insulin, Long-Acting