Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5)

TY - JOUR

T1 - Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5)

T2 - A Randomized Trial

AU - Bajaj, Harpreet S

AU - Aberle, Jens

AU - Davies, Melanie

AU - Donatsky, Anders Meller

AU - Frederiksen, Marie

AU - Yavuz, Dilek G

AU - Gowda, Amoolya

AU - Lingvay, Ildiko

AU - Bode, Bruce

PY - 2023/11

Y1 - 2023/11

N2 - 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.

AB - 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.

KW - Adult

KW - Humans

KW - Blood Glucose

KW - Diabetes Mellitus, Type 2/drug therapy

KW - Hypoglycemia/drug therapy

KW - Hypoglycemic Agents/therapeutic use

KW - Insulin/therapeutic use

KW - Insulin Glargine/therapeutic use

KW - Mobile Applications

U2 - 10.7326/M23-1288

DO - 10.7326/M23-1288

M3 - SCORING: Journal article

C2 - 37748181

VL - 176

SP - 1476

EP - 1485

JO - ANN INTERN MED

JF - ANN INTERN MED

SN - 0003-4819

IS - 11

ER -