BACKGROUND Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden. OBJECTIVE To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice. DESIGN 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626). SETTING 176 sites in 7 countries. PARTICIPANTS 1085 insulin-naive adults with T2D. INTERVENTION Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300). MEASUREMENTS The primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score). RESULTS The estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P < 0.001) and superiority (P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments. LIMITATION Inability to differentiate the effects of icodec and the dosing guide app. CONCLUSION Compared with OD analogues, icodec with app showed superior HbA1c reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates. PRIMARY FUNDING SOURCE Novo Nordisk A/S.

Background: Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.Objective: To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice.Design: 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626)Setting: 176 sites in 7 countries.Participants: 1085 insulin-naive adults with T2D.Intervention: Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300).Measurements: The primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score).Results: The estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P < 0.001) and superiority (P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments.Limitation: Inability to differentiate the effects of icodec and the dosing guide app.Conclusion: Compared with OD analogues, icodec with app showed superior HbA1c reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates.Primary Funding Source: Novo Nordisk A/S.

Question Does PPG-focused titration of URLi demonstrate increase glycaemic control in patients with T1D?

To investigate whether an increased bolus: basal insulin ratio (BBR) with liver‐targeted bolus insulin (BoI) would increase BoI use and decrease hypoglycaemic events (HEv).

Importance:Diabetic retinopathy (DR) is a leading cause of blindness in adults worldwide. Early detection and intervention can prevent blindness; however, many patients do not receive their recommended annual diabetic eye examinations, primarily owing to limited access.Objective:To evaluate the safety and accuracy of an artificial intelligence (AI) system (the EyeArt Automated DR Detection System, version 2.1.0) in detecting both more-than-mild diabetic retinopathy (mtmDR) and vision-threatening diabetic retinopathy (vtDR).Design, Setting, and Participants:A prospective multicenter cross-sectional diagnostic study was preregistered (NCT03112005) and conducted from April 17, 2017, to May 30, 2018. A total of 942 individuals aged 18 years or older who had diabetes gave consent to participate at 15 primary care and eye care facilities. Data analysis was performed from February 14 to July 10, 2019.Interventions:Retinal imaging for the autonomous AI system and Early Treatment Diabetic Retinopathy Study (ETDRS) reference standard determination.Main Outcomes and Measures:Primary outcome measures included the sensitivity and specificity of the AI system in identifying participants' eyes with mtmDR and/or vtDR by 2-field undilated fundus photography vs a rigorous clinical reference standard comprising reading center grading of 4 wide-field dilated images using the ETDRS severity scale. Secondary outcome measures included the evaluation of imageability, dilated-if-needed analysis, enrichment correction analysis, worst-case imputation, and safety outcomes.Results:Of 942 consenting individuals, 893 patients (1786 eyes) met the inclusion criteria and completed the study protocol. The population included 449 men (50.3%). Mean (SD) participant age was 53.9 (15.2) years (median, 56; range, 18-88 years), 655 were White (73.3%), and 206 had type 1 diabetes (23.1%). Sensitivity and specificity of the AI system were high in detecting mtmDR (sensitivity: 95.5%; 95% CI, 92.4%-98.5% and specificity: 85.0%; 95% CI, 82.6%-87.4%) and vtDR (sensitivity: 95.1%; 95% CI, 90.1%-100% and specificity: 89.0%; 95% CI, 87.0%-91.1%) without dilation. Imageability was high without dilation, with the AI system able to grade 87.4% (95% CI, 85.2%-89.6%) of the eyes with reading center grades. When eyes with ungradable results were dilated per the protocol, the imageability improved to 97.4% (95% CI, 96.4%-98.5%), with the sensitivity and specificity being similar. After correcting for enrichment, the mtmDR specificity increased to 87.8% (95% CI, 86.3%-89.5%) and the sensitivity remained similar; for vtDR, both sensitivity (97.0%; 95% CI, 91.2%-100%) and specificity (90.1%; 95% CI, 89.4%-91.5%) improved.Conclusions and Relevance:This prospective multicenter cross-sectional diagnostic study noted safety and accuracy with use of the EyeArt Automated DR Detection System in detecting both mtmDR and, for the first time, vtDR, without physician assistance. These findings suggest that improved access to accurate, reliable diabetic eye examinations may increase adherence to recommended annual screenings and allow for accelerated referral of patients identified as having vtDR.