Rationale and design of the phase 3a development programme (<scp>ONWARDS</scp> 1–6 trials) investigating once‐weekly insulin icodec in diabetes

Philis‐Tsimikas, Athena; Bajaj, Harpreet S.; Begtrup, Kamilla; Cailleteau, Roman; Gowda, Amoolya; Lingvay, Ildiko; Mathieu, Chantal; Russell‐Jones, David; Rosenstock, Julio

doi:10.1111/dom.14871

Cited by 47 publications

(62 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, prebreakfast SMBG values were similar between treatment groups, leading to comparable dose titration and total weekly insulin dose during the last 2 weeks of treatment. Further evaluation of continuous glucose monitoring data from other ONWARDS trials may clarify these findings …”

Section: Discussionmentioning

confidence: 97%

“…Description of the statistical analyses has been published previously. 7 Efficacy end points were analyzed using the full analysis set (all participants randomized) and the in-trial period. Safety end points were evaluated using the safety analysis set (all randomized participants who received ≥1 dose of trial treatment) and the treatment period, the time during which participants were exposed to treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Description of the statistical analyses has been published previously . Efficacy end points were analyzed using the full analysis set (all participants randomized) and the in-trial period.…”

Section: Methodsmentioning

confidence: 99%

“…Clinical trials have demonstrated that icodec has a long half-life of approximately 1 week, with phase 2 trials in people with type 2 diabetes demonstrating similar glycemic efficacy and safety profiles for icodec and once-daily insulin glargine U100 . ONWARDS is a phase 3a clinical trial program that comprises 6 trials investigating the efficacy and safety of icodec in various clinical scenarios . In the ONWARDS 4 and ONWARDS 2 trials, among participants with insulin-treated type 2 diabetes, hemoglobin A 1c (HbA 1c ) reductions were similar or better with icodec than once-daily insulin glargine U100 or insulin degludec, with no statistically significant differences in level 2 or 3 hypoglycemia rates …”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6] ONWARDS is a phase 3a clinical trial program that comprises 6 trials investigating the efficacy and safety of icodec in various clinical scenarios. 7 In the ONWARDS 4 and ONWARDS 2 trials, among participants with insulintreated type 2 diabetes, hemoglobin A 1c (HbA 1c ) reductions were similar or better with icodec than once-daily insulin glargine U100 or insulin degludec, with no statistically significant differences in level 2 or 3 hypoglycemia rates. 8,9 This study reports the results of the ONWARDS 3 trial, which assessed the efficacy and safety of once-weekly icodec vs oncedaily degludec in people with insulin-naive type 2 diabetes.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes

Lingvay

Asong

Desouza

et al. 2023

JAMA

Self Cite

View full text Add to dashboard Cite

ImportanceOnce-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes.ObjectiveTo evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes.Design, Setting, and ParticipantsRandomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol).InterventionsParticipants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n = 294) or once-daily degludec and once-weekly placebo (degludec group; n = 294).Main Outcomes and MeasuresThe primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level &lt;54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes.ResultsAmong 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], −0.2 [95% CI, −0.3 to −0.1] percentage points), confirming noninferiority (P &lt; .001) and superiority (P = .002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, −6 to 5] mg/dL; P = .90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, −0.19 to 1.10] kg; P = .17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P = .11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P = .01).Conclusions and RelevanceAmong people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups.Trial RegistrationClinicalTrials.gov Identifier: NCT04795531

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes

Lingvay

Asong

Desouza

et al. 2023

JAMA

Self Cite

View full text Add to dashboard Cite

show abstract

Once-weekly insulins: a promising approach to reduce the treatment burden in people with diabetes

Trevisan,

Conti,

Ciardullo

2024

Diabetologia

View full text Add to dashboard Cite

Despite the availability of new classes of glucose-lowering drugs that improve glycaemic levels and minimise long-term complications, at least 20–25% of people with type 2 diabetes require insulin therapy. Moreover, a substantial proportion of these individuals do not achieve adequate metabolic control following insulin initiation. This is due to several factors: therapeutic inertia, fear of hypoglycaemia and/or weight gain, poor communication, complexity of insulin titration, and the number of injections needed, with the associated reduced adherence to insulin therapy. Once-weekly insulins provide a unique opportunity to simplify basal insulin therapy and to allow good glycaemic control with a low risk of hypoglycaemia. Several approaches to developing a stable and effective once-weekly insulin have been proposed, but, to date, insulin icodec and basal insulin Fc (insulin efsitora alfa) are the only two formulations for which clinical studies have been reported. The results of Phase I and II studies emphasise both efficacy (in term of glucose levels) and potential risks and adverse events. Phase III studies involving insulin icodec are reassuring regarding the risk of hypoglycaemia compared with daily basal insulin analogues. Despite some concerns raised in ongoing clinical trials, the available data suggest that weekly insulins may also be an option for individuals with type 1 diabetes, especially when adherence is suboptimal. For the first time there is an opportunity to make an important breakthrough in basal insulin therapy, particularly in people with type 2 diabetes, and to improve not only the quality of life of people with diabetes, but also the practice of diabetologists. Graphical Abstract

show abstract

Counseling for Insulin Icodec: A Proposed Practitioner’s Guide

Kalra,

Bhattacharya,

Kapoor

2024

Diabetes Ther

View full text Add to dashboard Cite

Despite insulin being a lifesaving medication, insulin distress, insulin hesitancy, and insulin inertia remain oft-repeated themes in diabetes discourse. The current model lists three issues: temperament, troublesomeness, and technicality, which contribute to insulin perceptions. Therapeutic patienteducation (TPE), value-added therapy (VAT), and medication counseling are concepts that assist in optimizing insulin perceptions. Insulin icodec is a basal insulin with a half-life of 196 h and a once-weekly or circaseptan frequency of administration. Insulin icodec reduces the frequency of basal insulin administration to one-seventh, which along with the lower requirement of glucose monitoring, reduces the burden of plastic and ancillary supply disposal. Because of its unique frequency of injection, insulin icodec usage requires appropriate counseling and education. This reader-friendly counseling guide helps practitioners offer VAT, as well as TPE while prescribing icodec and other insulins.

show abstract

Rationale and design of the phase 3a development programme (ONWARDS 1–6 trials) investigating once‐weekly insulin icodec in diabetes

Cited by 47 publications

References 15 publications

Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes

Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes

Once-weekly insulins: a promising approach to reduce the treatment burden in people with diabetes

Counseling for Insulin Icodec: A Proposed Practitioner’s Guide

Contact Info

Product

Resources

About