Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial

Mathieu, Chantal; Àsbjörnsdóttir, Björg; Bajaj, Harpreet S.; Lane, Wendy; Matos, Ana Laura de Souza Almeida; Sreenivasamurthy, L; Stachlewska, Karolina; Rosenstock, Julio

doi:10.1016/s0140-6736(23)00520-2

Cited by 49 publications

(64 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Concern over injection site reactions has not been raised in other icodec trials to date, and this finding remains unexplained. [3][4][5][6]8,9 Additionally, although the occurrence of diabetic retinopa-thy was higher with icodec than degludec, the absolute numerical difference was small. No difference in retinopathy events between groups has been observed in other icodec trials to date.…”

Section: Discussionmentioning

confidence: 96%

“…The number of injection site reactions was numerically higher with icodec than degludec. Concern over injection site reactions has not been raised in other icodec trials to date, and this finding remains unexplained . Additionally, although the occurrence of diabetic retinopathy was higher with icodec than degludec, the absolute numerical difference was small.…”

Section: Discussionmentioning

confidence: 97%

“…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%

“…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 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

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: 96%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 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

View full text Add to dashboard Cite

show abstract

“…Once-weekly insulin icodec was compared with oncedaily insulin glargine U100 with 2-4 daily bolus insulin aspart injections in 582 persons with type 2 diabetes treated for 26 weeks, finding similar 1.2% reductions in HbA1c from 8.3% baseline, 32 vs 29 mg/dL reduction in fasting glucose, 2.7 vs 2.2 kg increases in body weight, and similar 37% vs 45% rates of level 1 hypoglycemia and 19% vs 25% rates of level 2 or 3 hypoglycemia. 11 Reports of insulin icodec in type 1 diabetes 12 and in insulin-naïve type 2 diabetes 13 also show improvement in glycemia similar to that with once daily insulin degludec, suggesting that it may soon be possible to use once weekly gut hormone-based treatment and once weekly insulin, an approach likely to greatly improve the acceptability of such approaches to our patients.…”

Section: Insulin Treatmentmentioning

confidence: 99%

A diabetes update

Bloomgarden

2023

Journal of Diabetes

View full text Add to dashboard Cite

Clinical Outcomes With Once‐Weekly Insulin Icodec Versus Once‐Daily Insulin Glargine U100 in Insulin‐Naïve and Previously Insulin‐Treated Individuals With Type 2 Diabetes: A Meta‐Analysis of Randomised Controlled Trials

Ahmed,

Shafiq,

Javaid

et al. 2024

Endocrino Diabet & Metabol

View full text Add to dashboard Cite

AimsThe once‐weekly insulin icodec, a new basal insulin analog, may positively support a reduction in injection frequency and improve adherence to therapy in type 2 diabetes (T2D). This study aimed to evaluate the safety and efficacy of insulin icodec compared with those of once‐daily glargine U100.MethodsA comprehensive literature search was conducted using PubMed/MEDLINE, Embase and the Cochrane Library from inception till September 2023. Data about clinical outcomes in both groups were extracted. Forest plots were generated using the random‐effects model by pooling odds ratios (ORs) and mean differences (MDs).ResultsFive randomised controlled trials and 2019 individuals with T2DM were included. In the pooled analysis, time in range was significantly higher (MD = 4.35; 95% CI: 1.65 to 7.05; p = 0.002) in the icodec group than in the once‐daily glargine group. The HbA1c levels were significantly reduced (MD = −0.13; 95% CI: −0.24 to −0.03; p = 0.02) in the weekly icodec group compared with those in the once‐daily glargine group. The weight gain was significantly less in the glargine group than in the weekly icodec group (MD = 0.41; 95% CI: 0.04 to 0.78; p = 0.03); however, in the subgroup analysis, this change became statistically insignificant in both insulin‐naïve and previously insulin‐treated individuals. The results were comparable across two groups for fasting plasma glucose levels, hypoglycaemia alert (Level 1), clinically significant (Level 2) or severe hypoglycaemia (Level 3), and adverse events.ConclusionInsulin icodec was associated with a reduction in glycated haemoglobin levels and higher time in range, with a similar safety profile as compared to insulin glargine U100. However, further evidence is still needed to reach a definitive conclusion.

show abstract

Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial

Cited by 49 publications

References 21 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

A diabetes update

Clinical Outcomes With Once‐Weekly Insulin Icodec Versus Once‐Daily Insulin Glargine U100 in Insulin‐Naïve and Previously Insulin‐Treated Individuals With Type 2 Diabetes: A Meta‐Analysis of Randomised Controlled Trials

Contact Info

Product

Resources

About