Awiqli (insulin icodec) / Novo Nordisk - LARVOL DELTA

Once-weekly insulin icodec vs. daily insulin glargine in type 2 diabetes: a meta-analysis with longitudinal insights. (PubMed, Ann Med Surg (Lond)) - "Insulin icodec provides a safe and effective alternative to once-daily insulin glargine for T2DM management, offering similar glycemic control with a once-weekly dosing regimen. The reduced injection burden may enhance adherence and treatment satisfaction, potentially improving long-term disease outcomes."

Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison Study of Insulin GZR4 With Insulin Degludec (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: Gan and Lee Pharmaceuticals, USA

New P1 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Awiqli® - erstes Wocheninsulin. (PubMed, MMW Fortschr Med) - No abstract available

Journal

Cost-effectiveness of insulin icodec for the treatment of type 2 diabetes in Canada. (PubMed, J Med Econ) - "Outcomes were expressed as quality-adjusted life-years (QALYs) and cost-effectiveness as incremental cost utility ratios (ICUR [cost/QALY]).ResultsIn all analyses, insulin icodec dominated insulin degludec and insulin detemir. Compared to insulin glargine U100 and U300, insulin icodec was associated with ICURs of $17,876, $20,844, and $73,253; and $6,439, $8,623, and $45,433 in the IN, BIE, and BBIE populations, respectively.LimitationsLimitations of this economic evaluation include the lack of data for some treatments in certain NMAs, uncertainty regarding the use of the NMA results for a 40-year time horizon, heterogeneous sources of disutilities, and uncertainty regarding the HRQoL benefits of reduced injection frequency.ConclusionsInsulin icodec is a cost-effective treatment option for adult patients with T2D versus once daily basal insulin-analogues publicly reimbursed in Canada."

HEOR • Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Continuous glucose monitoring-derived model-based postprandial glucose with IcoSema vs other insulin regimens: a post hoc analysis of COMBINE 1 and 3 (EASD 2025) - P3 | "Supported by Study funded by Novo Nordisk A/S Clinical Trial Registration Number: COMBINE 1 (NCT05352815); COMBINE 3 (NCT05013229) Background and aims: This post hoc analysis investigated whether IcoSema, a once-weekly (OW) combination therapy of basal insulin icodec and the GLP-1 analogue semaglutide currently in development, offers a postprandial glucose (PPG) control benefit vs other insulin-based regimens.Materials and COMBINE 1 and 3, two 52-week, phase 3a trials, investigated IcoSema vs OW basal insulin (icodec; COMBINE 1) or basal-bolus therapy (glargine U100 + aspart; COMBINE 3) in adults with type 2 diabetes (T2D) who were inadequately controlled on daily basal insulin. Based on post hoc modelling using CGM data, IcoSema showed statistically significantly better PPG control vs OW basal insulin and similar PPG control vs basal-bolus therapy."

Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and hypoglycaemia outcomes with once-weekly insulin icodec vs once-daily basal insulin in type 2 diabetes by diabetes duration: ONWARDS 1-5 (EASD 2025) - P3 | "Efficacy and hypoglycaemia outcomes for icodec vs OD comparators were overall similar across T2D duration subgroups."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

A Research Study to See How Well New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Levels in People With Type 2 Diabetes (T2D), Compared to Daily Insulin Glargine (COMBINE 4) (clinicaltrials.gov) - P3 | N=485 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Clinical Use of Once-Weekly Insulin Icodec: Translating Clinical Trial Data into Practical Guidance for Diabetes Management. (PubMed, Drugs) - P3 | "Finally, we also briefly summarize the available evidence on icodec use in individuals with T1D, although the primary focus of this review is on its use in T2D. This review provides a comprehensive information resource for HCPs regarding the use of icodec in clinical practice."

Clinical • Journal • Review • Diabetes • Metabolic Disorders • Pediatrics • Renal Disease • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Efficacy and safety of once-weekly basal insulin therapy in people with type 1 diabetes: a systematic review and meta-analysis (EASD 2025) - "We included randomized controlled trials (RCTs) comparing insulin icodec and efsitora against once-daily basal insulins in people with type 1 diabetes... This meta-analysis for the first time evaluated efficacy and safety of once-weekly basal insulins in the treatment of adults with type 1 diabetes, showing similar glucose-lowering effect with increased hypoglycemia occurrence and divergent findings on treatment satisfaction compared to once-daily compounds."

Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

A Research Study to See How a New Weekly Insulin, Insulin Icodec When Given Along With Semaglutide Helps in Reducing the Blood Sugar Level in Patients With Type 2 Diabetes (clinicaltrials.gov) - P3 | N=148 | Completed | Sponsor: Novo Nordisk A/S | Recruiting ➔ Completed | Trial primary completion date: Sep 2024 ➔ Apr 2025

Trial completion • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A Research Study to See How Well Weekly Insulin Icodec Maintains Blood Sugar Levels Compared to Daily Basal Insulins in Adults With Type 2 Diabetes (clinicaltrials.gov) - P4 | N=586 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P4 trial • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Gastrointestinal adverse events with once-weekly IcoSema: a post hoc analysis of COMBINE 1-3 (EASD 2025) - P3 | "Supported by Medical writing support was provided by Oxford PharmaGenesis, funded by Novo Nordisk A/S Clinical Trial Registration Number: NCT05352815 (COMBINE 1); NCT05259033 (COMBINE 2); NCT05013229 (COMBINE 3) Background and aims: The efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a glucagon-like peptide-1 [GLP-1] analogue), were assessed in three 52-week, phase 3a trials (COMBINE 1-3). In participants receiving IcoSema, regardless of experiencing GIAEs, changes in HbA1c, body weight and actual weekly insulin dose over the treatment period, were broadly consistent with the overall findings reported for the COMBINE trials."

Adverse events • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Continuous glucose monitoring-based outcomes in adults with type 2 diabetes receiving IcoSema vs comparators: post hoc analysis of COMBINE 1 and 3 (EASD 2025) - P3 | "Supported by Medical writing support was provided by Oxford PharmaGenesis, funded by Novo Nordisk A/S Clinical Trial Registration Number: COMBINE 1 (NCT05352815); COMBINE 3 (NCT05013229) Background and aims: IcoSema is a once-weekly combination therapy of basal insulin icodec (icodec) and the glucagon-like peptide-1 analogue semaglutide. Between weeks 48-52, TiTR was significantly higher with IcoSema vs icodec and similar vs BBT. More participants on IcoSema vs comparators achieved the CGM composite outcome, CV% was <36% and median overall hypoglycaemia duration was similar between arms."

Clinical • Retrospective data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

ONWARDS 11: A Research Study to See How a Weekly Insulin, Insulin Icodec, Helps in Reducing the Blood Sugar Compared to Daily Insulin Glargine, Both in Combination With Insulin Aspart, in Adults With Type 1 Diabetes (clinicaltrials.gov) - P3 | N=877 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Improved treatment satisfaction with once-weekly IcoSema vs daily basal-bolus therapy in adults with type 2 diabetes inadequately controlled on daily basal insulin: COMBINE 3 (EASD 2025) - P3 | "Supported by Medical writing support was provided by Oxford PharmaGenesis, funded by Novo Nordisk A/S Clinical Trial Registration Number: NCT05013229 (COMBINE 3) Background and aims: COMBINE 3 evaluated the efficacy and safety of IcoSema, a once-weekly combination of basal insulin icodec and the glucagon-like peptide-1 analogue semaglutide, vs daily basal-bolus therapy (BBT) in adults with type 2 diabetes (T2D). The statistically significant estimated improvement in the total treatment satisfaction score with once-weekly IcoSema vs daily BBT appeared to be driven by satisfaction with current treatment, convenience, flexibility, willingness to recommend treatment to others and satisfaction to continue trial treatment."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Adherence to app-based dose guidance for once-weekly insulin icodec in insulin-naive individuals with type 2 diabetes: Post hoc analysis of ONWARDS 5. (PubMed, Diabetes Obes Metab) - P3 | "Greater adherence to app-based dose guidance was associated with greater estimated improvements in pre-breakfast SMBG and higher weekly insulin dose. Trends indicated HbA1c improvements in all adherence subgroups. Findings support app use for real-world insulin titration."

Journal • Retrospective data • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Efficacy and hypoglycaemia outcomes with once-weekly insulin icodec vs once-daily basal insulin in type 2 diabetes by baseline HbA1c: ONWARDS 1-5 (EASD 2025) - P3 | "Efficacy and hypoglycaemia outcomes for icodec vs OD comparators were overall similar across baseline HbA1c subgroups."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Efficacy and hypoglycaemia outcomes of once-weekly IcoSema in type 2 diabetes according to pre-trial sodium-glucose cotransporter-2 inhibitor use: a post hoc analysis of COMBINE 1-3 (EASD 2025) - P3 | "Clinical Trial Registration Number: COMBINE 1 (NCT05352815); COMBINE 2 (NCT05259033); COMBINE 3 (NCT05013229) Background and aims: IcoSema (a once-weekly combination therapy of insulin icodec [icodec] and semaglutide, a glucagon-like peptide-1 analogue) has been investigated in three 52-week, phase 3a trials (COMBINE 1-3). Overall, efficacy and hypoglycaemia outcomes were generally consistent with IcoSema vs comparators among adults with T2D, irrespective of pre-trial SGLT2i use."

Clinical • Retrospective data • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Continuous Glucose Monitoring Metrics and Continuous Glucose Monitoring-Based Hypoglycemia, Including Duration, in Individuals with Type 1 Diabetes Switching to Once-Weekly Insulin Icodec: A Post Hoc Evaluation of ONWARDS 6. (PubMed, Diabetes Technol Ther) - "Background: Post hoc evaluation of ONWARDS 6 assessed continuous glucose monitoring (CGM) metrics and CGM-based hypoglycemia with once-weekly insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes. In adults with type 1 diabetes, estimated rate ratios for CGM-based clinically significant hypoglycemia were lower than those estimated from SMBG data, although still favoring degludec with estimated rate ratios of 1.28-1.38. CGM metrics varied by treatment day after icodec injection, but median duration of CGM-based hypoglycemia was comparable between treatment arms."

Journal • Retrospective data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Ten-fold Insulin Icodec Overdose: A Case Report. (PubMed, Can J Diabetes) - No abstract available

Journal

An overview of randomized clinical trials of fixed-ratio combinations of basal insulin plus GLP-1RA (injectable therapy): Lessons for advancing therapy in people with type 2 diabetes. (PubMed, Diabetes Obes Metab) - "BI and GLP-1RAs can be administered separately or as fixed-ratio combinations (FRCs) for daily use (degludec+liraglutide, IDegLira, glargine-100 + lixisenatide iGlarLixi) or weekly use (icodec+semaglutide, IcoSema)...The weekly FRC IcoSema is superior to weekly insulin icodec (COMBINE 1), to semaglutide (COMBINE 2), and non-inferior to basal-bolus insulin therapy (COMBINE 3)...However, all FRCs are limited by the low GLP-1RA dose relative to the insulin delivered. Whenever higher GLP-1RA doses are required (i.e., in obese people), the option of separate dosing of BI and GLP-1RA with independent titration of each component should be considered."

Clinical • Journal • Atherosclerosis • Cardiovascular • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Once-Weekly versus Daily Basal Insulin in Type 2 Diabetes: A Systematic Review and Meta-Analysis (ENDO 2025) - "To improve patient adherence and convenience, once-weekly basal insulin analogs such as insulin icodec and insulin Fc have been developed... This meta-analysis demonstrates significant improvements in HbA1c and TIR with once-weekly basal insulin in T2DM at the cost of more hypoglycemic events. There was no difference in the benefit of weekly insulin on HbA1c reduction, in regards to insulin naivety status."

Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

A Research Study to See How Switching From a Daily Basal Insulin to a New Weekly Insulin, Insulin Icodec, Helps in Reducing the Blood Sugar Compared to Daily Insulin Glargine in Adults With Type 2 Diabetes (clinicaltrials.gov) - P3 | N=429 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Once-weekly basal insulin therapy in type 1 diabetes: A paradigm shift or a work in progress? (PubMed, Am J Health Syst Pharm) - "Once-weekly basal insulin represents a potential paradigm shift in T1DM management, offering convenience but presenting challenges related to hypoglycemia risk, patient acceptance, and regulatory hurdles. Further research is needed to refine titration protocols, identify optimal patient populations, and address safety concerns before these therapies can become standard of care."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • IR

CGM-Based Outcomes in Adults with T2D Receiving IcoSema vs. Comparators—Post Hoc Analysis of COMBINE 1 and 3 (ADA 2025) - "Introduction and Objective: IcoSema is a once-weekly combination therapy of insulin icodec (icodec) + semaglutide... Between weeks 48-52, TiTR was significantly higher with IcoSema vs icodec and similar vs BBT. More participants on IcoSema vs comparators achieved the CGM composite outcome, CV% was <36% and median overall hypoglycemia duration was similar between arms."

Clinical • Retrospective data • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus