AUTONOMY: the first randomized trial comparing two patient-driven approaches to initiate and titrate prandial insulin lispro in type 2 diabetes

Diabetes Care. 2014 Aug;37(8):2132-40. doi: 10.2337/dc13-2664. Epub 2014 Apr 17.

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.

Research design and 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Insulin Glargine
  • Insulin Lispro / administration & dosage*
  • Insulin Lispro / adverse effects
  • Insulin, Long-Acting / administration & dosage*
  • Male
  • Middle Aged
  • Treatment Outcome
  • Young Adult

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin Lispro
  • Insulin, Long-Acting
  • Insulin Glargine