Automated insulin dosing guidance to optimise insulin management in patients with type 2 diabetes: a multicentre, randomised controlled trial

Background Insulin therapy is most effective if dosage titrations are done regularly and frequently, which is seldom practical for most clinicians, resulting in an insulin titration gap. The d-Nav Insulin Guidance System (Hygieia, Livonia, MI, USA) is a handheld device that is used to measure glucose, determine glucose patterns, and automatically determine the appropriate next insulin dose. We aimed to determine whether the combination of the d-Nav device and health-care professional support is superior to health-care professional support alone. Methods In this multicentre, randomised, controlled study, we recruited patients from three diabetes centres in the USA (in Detroit MI; Minneapolis, MN; and Des Moines IA). Patients were eligible if they were aged 21-70 years, diagnosed with type 2 diabetes with a glycated haemoglobin (HbA(1c)) concentration of 7.5% or higher (>= 58 mmol/mol) and 11% or lower (<= 97 mmol/mol), and had been using the same insulin regimen for the previous 3 months. Exclusion criteria included body-mass index of 45 kg/m (2) or higher; severe cardiac, hepatic, or renal impairment; and more than two severe hypoglycaemic events in the past year. Eligible participants were randomly assigned (1: 1), with randomisation blocked within each site, to either d-Nav and health-care professional support (intervention group) or health-care professional support alone (control group). Both groups were contacted seven times (three face-to-face and four phone visits) during 6 months of follow-up. The primary objective was to compare average change in HbA(1c) from baseline to 6 months. Safety was assessed by the frequency of hypoglycaemic events. The primary objective and safety were assessed in the intention-to-treat population. We used Student's t test to assess the primary outcome for statistical significance. This study was registered with ClinicalTrials. gov, number NCT02424500. Findings Between Feb 2, 2015, and March 17, 2017, 236 patients were screened for eligibility, of whom 181 (77%) were enrolled and randomly assigned to the intervention (n= 93) and control (n= 88) groups. At baseline, mean HbA(1c) was 8.7% (SD 0.8; 72 mmol/mol [SD 8.8]) in the intervention group and 8.5% (SD 0.8; 69 mmol/mol [SD 8.8]) in the control group. The mean decrease in HbA(1c) from baseline to 6 months was 1.0% (SD 1.0; 11 mmol/mol [SD 11]) in the intervention group, and 0.3% (SD 0.9; 3.3 mmol/mol [9.9]) in the control group (p< 0.0001). The frequency of hypoglycaemic events per month was similar between the groups (0.29 events per month [SD 0.48] in the intervention group vs 0.29 [SD 1.12] in the control group; p= 0.96). Interpretation The combination of automated insulin titration guidance with support from health-care professionals offers superior glycaemic control compared with support from health-care professionals alone. Such a solution facilitated safe and effective insulin titration in a large group of patients with type 2 diabetes, and now needs to be evaluated across large health-care systems to confirm these findings and study cost-effectiveness. Funding US National Institutes of Health, National Institute of Digestive and Kidney Diseases. Copyright (c) 2019 Elsevier Ltd. All rights reserved.