Awiqli (insulin icodec) / Novo Nordisk - LARVOL DELTA

Where Are We With Weekly Insulin? The Pros and Cons (AACE 2026) - "Insulin icodec is approved for use in the European Union, Canada, Australia, Japan, and Switzerland, but not the US...One faculty member could have experience in the clinical trials with the weekly insulins, and another could give a view from the regulatory perspective. Learning Objectives: After participating in this session, attendees should be able to explain the pharmacokinetic and pharmacological properties of weekly insulins.After participating in this session, attendees should be able to identify three type of patients who might benefit from once weekly basal insulins.After participating in this session, attendees should be able to assess the safety and efficacy of weekly insulins in type 1 diabetes."

Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Once-weekly insulin icodec versus once-daily insulin degludec for type 2 diabetes in China: A cost-utility and budget impact analysis. (PubMed, Diabetes Obes Metab) - "Within the current reimbursement context in China, once-weekly icodec is a dominant strategy compared with degludec, offering greater health benefits at a lower cost for patients with type 2 diabetes and generating potential annual savings."

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

Efficacy and hypoglycaemia outcomes of once-weekly insulin icodec versus once-daily basal insulin comparators across baseline HbA1c, BMI and duration of type 2 diabetes subgroups: A post hoc analysis of ONWARDS 1-5. (PubMed, Diabetes Obes Metab) - "The efficacy and hypoglycaemia profile of icodec versus OD basal insulin comparators was overall consistent across trial populations irrespective of baseline HbA1c, BMI or T2D duration."

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

Once-weekly administration of insulin in the real-world management of type 2 diabetes. A Delphi-like consensus. (PubMed, Acta Diabetol) - "The advent of once-weekly insulin icodec therapy is an unprecedent breakthrough in diabetes care. Compared with once-daily insulin analogues, it offers a simplified, secure, enhanced, and sustained glycemic control, counteracting therapeutic inertia, expectedly improving adherence to insulin therapy. Insulin icodec can not only enable personalized treatment and positively impact the clinical outcome, but also improve patient satisfaction and overall quality of life."

Journal • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A Research Study to See How Insulin Icodec Helps People With Type 1 Diabetes Control Their Blood Sugar (clinicaltrials.gov) - P=N/A | N=245 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Real-world evidence • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

A Phase IIIb Clinical Study to Assess the Efficacy and Safety of GZR4 in Subjects With Type 2 Diabetes Mellitus Treated With Basal Insulin (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Gan & Lee Pharmaceuticals. | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

The safety of novel once-weekly insulins in the management of diabetes. (PubMed, Expert Opin Drug Saf) - "This narrative review summarizes the characteristics, advantages, and drawbacks of the two OWI products on the market and in development, namely insulin icodec and insulin efsitora...However, increased risks of hypoglycemia and weight gain were seen in some studies. The clinical concerns regarding hypoglycemia led the US regulatory agency to vote against recommending approval of icodec for use in patients with type 1 diabetes."

Journal • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

The Long-Term Cost-Effectiveness of Insulin Icodec vs. Once-Daily Basal Insulin Analogs in Italy (ISPOR-EU 2025) - "OBJECTIVES: Daily basal insulin injections remain a cornerstone of type 2 diabetes (T2D) management, yet their frequency can impose a considerable burden on patients' quality of life. Based on a willingness-to-pay range of EUR 25,000-40,000 per QALY gained, icodec was projected to be highly cost-effective for treating insulin-naïve people with T2D in Italy, resulting from a reduced injection burden and a lowered incidence of diabetes-related complications."

Cost effectiveness • HEOR • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Systematic Review of the Cost-Effectiveness of Insulin Therapies in the Treatment of Type 2 Diabetes (ISPOR-EU 2025) - "Insulin icodec showed both cost savings (USD 479.96-974.01) and improved outcomes (0.04-0.08 QALYs) versus insulin degludec. Insulin glargine 100 was cost-effective compared to NPH insulin (ICERs USD 423.85-21,589.82) and dominant over insulin detemir... SR highlights the cost-effectiveness of various insulin therapies and offers valuable data for future pharmacoeconomic research. However, studies from Southeast Asia, including Vietnam, remain limited, indicating a need for further regional research."

Cost effectiveness • HEOR • Review • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

An Adjusted Indirect Comparison of Once-Weekly Insulin Efsitora Alfa vs. Insulin Icodec for Adults With Type 2 Diabetes Mellitus Previously Treated With Basal Insulin (ISPOR-EU 2025) - "Efsitora showed comparable results to icodec for all efficacy, composite and key safety endpoints in individuals with T2DM previously treated with basal insulin."

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

An Adjusted Indirect Comparison of Once-Weekly Insulin Efsitora Alfa vs. Insulin Icodec for Adults With Type 2 Diabetes Mellitus Previously Treated With Basal-Bolus Insulin (ISPOR-EU 2025) - "Efsitora showed comparable results to icodec for key efficacy and safety endpoints in adults with T2DM previously treated with basal-bolus insulin."

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

Cost-Effectiveness of Once-Weekly Insulin Icodec versus Daily Basal Insulins in Chinese Adults with T2DM: A Treatment-Background Stratified Analysis. (PubMed, Clinicoecon Outcomes Res) - "Insulin icodec offers cost-saving potential versus degludec in insulin-naïve T2DM patients. For basal and basal-bolus-treated patients, the clinical use of icodec needs to be critically evaluated for cost burden, and it is recommended that it be used preferentially in patients who are sensitive to the frequency of injections."

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

A Case of Insulin Edema Syndrome Improved by Weekly Insulin. (PubMed, JCEM Case Rep) - "Weekly insulin icodec was introduced, which was well-tolerated by the patient and improved her adherence to therapy and her insulin edema without significant weight gain. Insulin edema is a diagnosis of exclusion, and clinicians should be aware of this clinical entity. The use of third-generation long-acting insulin analog may be helpful in some patients with this syndrome."

Journal • Diabetes • Immunology • Metabolic Disorders • Type 2 Diabetes Mellitus

Is once-weekly insulin a viable alternative for type 2 diabetes? A meta-analysis of randomized controlled trials. (PubMed, Diabetol Int) - "Once-weekly novel insulin preparations such as Icodec and basal insulin Fc (BIF)/insulin Efsitora Alfa have raised hope among clinicians and patients when they were developed and evaluated in a series of clinical trials...No significant differences were observed between once-weekly and once-daily insulin for other safety outcomes. Once-weekly insulin regimen was superior in reducing HbA1c level while maintaining a similar safety profile to the once-daily insulin regimen, thus suggesting that such regimen may potentially be an alternative to the currently established once-daily basal insulin regimen."

Journal • Retrospective data • Diabetes • Metabolic Disorders • 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. (PubMed, Diabetes Obes Metab) - "This meta-analysis is the first to evaluate the efficacy and safety of once-weekly basal insulin therapy exclusively in adults with type 1 diabetes and including all published RCTs. The analysis demonstrated a similar glucose-lowering effect compared to once-daily basal insulin but revealed an increased occurrence of severe hypoglycaemia."

Journal • Retrospective data • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Pharmacokinetic Characteristics of a Once-Weekly Combination Therapy of Insulin Icodec and Semaglutide Versus Its Separate Components in Chinese Individuals with Type 2 Diabetes. (PubMed, Diabetes Ther) - P1 | "In Chinese individuals with T2D, icodec pharmacokinetics and semaglutide total exposure are unaffected when combining icodec and semaglutide in IcoSema. However, maximum semaglutide concentration is higher and occurs earlier with IcoSema. This information may help to ensure suitable dose recommendations for IcoSema."

Clinical • Journal • PK/PD data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Once-Weekly Insulin Icodec in Indian Participants with Diabetes: Results from ONWARDS 1, 4, and 6 Studies. (PubMed, Diabetes Ther) - P3 | "Icodec demonstrated comparable efficacy and safety to once-daily basal insulins in Indian participants with T1D and T2D. These findings support icodec as a viable option for insulin initiation or intensification in Indian clinical practice."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Novo Nordisk today announced the resubmission of its Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for Awiqli (insulin icodec) injection, a once-weekly basal insulin treatment for adults living with type 2 diabetes. (Novo Nordisk Press Release) - "The resubmission is based on results from the ONWARDS type 2 diabetes phase 3a program for once-weekly Awiqli which is comprised of five randomized, active-controlled, treat-to-target clinical trials in approximately 4,000 adults with type 2 diabetes."

FDA filing • 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 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Emerging perspectives on once-weekly insulins in type 1 and type 2 diabetes: a mini-review. (PubMed, Front Endocrinol (Lausanne)) - "The development of once-weekly basal insulin analogues, such as insulin icodec and efsitora alfa, represents a promising strategy to reduce injection burden and improve adherence in diabetes management...In type 1 diabetes, available data remain limited; however, the ONWARDS 6 and QWINT-5 trials demonstrated that once-weekly icodec and efsitora, respectively, achieved comparable reductions in HbA1c to once-daily insulin degludec, when used in combination with prandial insulin...Recent findings from the COMBINE program demonstrated that the fixed-ratio combination of icodec and semaglutide (IcoSema) produced superior HbA1c reductions compared to either agent alone, though not superior to a basal-bolus regimen with glargine and aspart insulin. However, several important questions remain to be addressed regarding once-weekly insulins, including their long-term efficacy on cardiovascular outcomes and overall long-term safety."

Clinical • Journal • Review • Cardiovascular • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

A Phase IIIb Clinical Study to Assess the Efficacy and Safety of GZR4 in Subjects With Type 2 Diabetes Mellitus Treated With Basal Insulin (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: Gan & Lee Pharmaceuticals.

New P3 trial • Diabetes • Metabolic Disorders • 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

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

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

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