Awiqli (insulin icodec) / Novo Nordisk - LARVOL DELTA

General Use-results Surveillance With Awiqli in Patients With Diabetes Mellitus (clinicaltrials.gov) - P=N/A | N=630 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

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

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

A1C and Hypoglycemia Outcomes with Once-Weekly IcoSema vs. Comparators in T2D by Kidney Function (ADA 2025) - "For IcoSema vs comparators, A1C reductions, combined clinically significant or severe hypoglycemia rates, and achievement of A1C <7% without weight gain and combined clinically significant or severe hypoglycemia were generally consistent across kidney function subgroups."

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

CGM-Derived Model-Based Postprandial Glucose with IcoSema vs. Other Insulin Regimens—A Post Hoc Analysis of COMBINE 1 and 3 (ADA 2025) - "Introduction and Objective: This post hoc analysis investigated whether IcoSema, a once-weekly (OW) combination therapy of basal insulin icodec and the GLP-1 analog semaglutide currently in development, offers a postprandial glucose (PPG) control benefit vs other insulin-based regimens. 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 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 • Metabolic Disorders

Efficacy and Hypoglycemia Outcomes with Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin in T2D by Baseline A1C—ONWARDS 1–5 (ADA 2025) - "Efficacy and hypoglycemia outcomes for icodec vs OD comparators were overall similar across baseline A1C subgroups."

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

Efficacy and Hypoglycemia Outcomes with Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin in T2D by Baseline BMI—ONWARDS 1–5 (ADA 2025) - "Efficacy and hypoglycemia outcomes for icodec vs OD comparators were overall similar across baseline BMI subgroups."

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

Efficacy and Hypoglycemia Outcomes with Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin in T2D by Diabetes Duration—ONWARDS 1–5 (ADA 2025) - "Efficacy and hypoglycemia outcomes for icodec vs OD comparators were overall similar across T2D duration subgroups."

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

Novo Nordisk to present array of new portfolio data including studies with semaglutide and CagriSema, expanding evidence in obesity and diabetes care at ADA 2025 (PRNewswire) - "Novo Nordisk today announced that new data from its industry-leading cardiometabolic portfolio will be showcased at the upcoming American Diabetes Association (ADA) 85th Scientific Sessions taking place in Chicago, June 20 – 23, 2025. A total of 29 abstracts will be presented, including trials investigating the efficacy and safety of CagriSema in people with overweight/obesity (REDEFINE 1) and those with overweight/obesity and type 2 diabetes (REDEFINE 2). Further, new data will complement the extensive body of cardiometabolic and kidney evidence for semaglutide in people with type 2 diabetes through analyses of the SOUL, STRIDE and FLOW trials, as well as insights from additional real-world studies in adults with obesity."

Clinical data • Obesity • Peripheral Arterial Disease • Type 2 Diabetes Mellitus

Once-weekly IcoSema versus multiple daily insulin injections in type 2 diabetes management (COMBINE 3): an open-label, multicentre, treat-to-target, non-inferiority, randomised, phase 3a trial. (PubMed, Lancet Diabetes Endocrinol) - P3 | "Once-weekly IcoSema achieved non-inferior HbA1c reduction and superiority in change in bodyweight, weekly total insulin dose, and hypoglycaemia rates versus daily BBT, suggesting that there is a potentially beneficial treatment intensification option for adults with type 2 diabetes."

Head-to-Head • Journal • P3 data • Alzheimer's Disease • Cognitive Disorders • Diabetes • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Once‑weekly IcoSema versus once‑weekly insulin icodec in type 2 diabetes management (COMBINE 1): an open‑label, multicentre, treat‑to‑target, randomised, phase 3a trial. (PubMed, Lancet Diabetes Endocrinol) - P3 | "In adults with inadequately controlled type 2 diabetes on daily basal insulin therapy, once‑weekly IcoSema showed superiority to once-weekly icodec alone in changes in HbA1c and in overall lower rate of combined clinically significant or severe hypoglycaemia. IcoSema might provide an option for insulin therapy intensification in adults with type 2 diabetes."

Journal • P3 data • Diabetes • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Metabolic Disorders • Severe Hypoglycemia • 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

Insights on Hospitalisations from the Phase 3a ONWARDS 1-6 Trials of Once-Weekly Insulin Icodec. (PubMed, Diabetes Ther) - P3 | "Similar numbers of hospitalisations were reported in both treatment arms. Icodec treatment was continued during hospitalisation in most participants and did not appear to have an impact on glycaemic management or hypoglycaemia. This analysis suggests that once-weekly icodec could be managed in a similar way to once-daily basal insulin analogues during hospitalisation."

Journal • P3 data • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

COMBINE 2 is better than one: shaping the future of therapeutics in inadequately controlled type 2 diabetes. (PubMed, Expert Rev Clin Pharmacol) - "The recently published COMBINE 2 trial reported that switching to weekly combination therapy of basal insulin icodec and semaglutide (IcoSema), compared with semaglutide, results in greater HbA1c reduction, similar risk of clinically significant or severe hypoglycemia, and comparable gastrointestinal tolerability, but unfavorable weight change among individuals with T2DM inadequately controlled with GLP-1 RA therapy, with or without additional oral glucose-lowering drugs. IcoSema represents an effective, safe, and convenient therapeutic choice for treatment intensification in individuals with T2DM inadequately controlled with GLP-1 RA therapy."

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

No Evidence of Increased Physical Activity-Related Hypoglycemia with Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin In Type 2 Diabetes-Onwards 1–5 (DDG 2025) - "The Incidence of Pa-Related Level 2 Or Level 3 Hypoglycemia in T2D Was Low in THE TRIAS OF Basal Insulins and was not worsted by Treatment with icodec VS OD Basal Insulin Comparators. Despite some uncertainty due to low incidences, thesis data are RESSURING."

Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin In individuals with type 2 diabetes by Kidney Function-Onwards 1–5 (DDG 2025) - "Overall, the Efficacy and Safety for Once-Weekly Icodec vs Od Comparators was consistent, with no trend across kidney function subgroups."

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

Impact of Age on the Efficacy and Safety of Once-Weekly Insulin Icodec vs. Once-Daily Insulin in Type 2 Diabetes (Onwards 1–5) (DDG 2025) - "Overall, Efficacy and Hypoglycemia Outcomes Were Consistent for Icodec VS OD Comparators Irespective of Age."

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

A Study to Test How a New Long-acting Insulin Works in the Body of Patients With Type 2 Diabetes During Exercise and Prolonged Fasting (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

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

Long-Term Cost-Effectiveness Analysis of Once-Weekly Insulin Icodec Versus Once-Daily Basal Insulin Analogues in Patients With Type 2 Diabetes in China (ISPOR 2025) - "Model inputs of baseline characteristics and treatment effects were derived from the ONWARDS 5 clinical trial, which compared icodec used with dosing guide app with once-daily basal insulins (glargine U100, glargine U300, and degludec). Once-weekly insulin icodec is a cost-effective treatment option compared to once-daily basal insulin analogues in China."

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

Long-Term Cost-Effectiveness of Once-Weekly Insulin Icodec Versus Degludec for the Treatment of Patients With Type 2 Diabetes Mellitus in China (ISPOR 2025) - "Compared with insulin degludec, insulin icodec represents a dominant treatment option for patients with T2DM in China."

Clinical • Cost effectiveness • HEOR • Cardiovascular • Diabetes • Diabetic Nephropathy • Macular Edema • Metabolic Disorders • Nephrology • Ophthalmology • Pain • Renal Disease • Retinal Disorders • Type 2 Diabetes Mellitus

Novo Nordisk expands in Korea with once-weekly insulin as obesity and hormone rivals circle (Korea Biomedical Review) - "Novo Nordisk’s once-weekly insulin, Awiqli (insulin icodec), is now officially available in Korea, marking a huge shift for diabetes patients long reliant on daily injections. But the Danish drugmaker isn’t just betting on convenience...For type 1 diabetes, it's used alongside bolus insulin—short-acting insulin taken at mealtimes—in Korea; for type 2, it can be administered solo or alongside oral antidiabetics, GLP-1 agonists (which help lower blood sugar and support weight loss), and/or bolus insulin."

Launch non-US • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

The effect of once-weekly insulin icodec vs once-daily basal insulin on physical activity-attributed hypoglycaemia in type 2 diabetes: a post hoc analysis of ONWARDS 1-5. (PubMed, Diabetologia) - P3 | "These findings do not suggest that there is an additional increase in hypoglycaemia risk attributed to physical activity with once-weekly basal icodec vs once-daily basal insulins in adults with type 2 diabetes."

Journal • Retrospective data • Alzheimer's Disease • Cognitive Disorders • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety Analysis of Practice Management Support Strategies of Once-weekly Insulin Icodec under the "in-person remote" Diabetes Self-Management Support Model: A Pragmatic Randomized Controlled Trial (ChiCTR) - P=N/A | N=160 | Not yet recruiting | Sponsor: Peking University First Hospital; Peking University First Hospital

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

Insulin icodec: A novel once-weekly formulation for the treatment of type 1 and type 2 diabetes mellitus. (PubMed, Rev Endocr Metab Disord) - "Hypoglycemia was similar or slightly increased with insulin icodec when compared to other long acting insulins. Overall, icodec is a useful, new formulation of basal insulin that allows for less injections, improved compliance, and potentially improved glycemic control providing a new tool to practitioners managing patients with diabetes who need to be on insulin."

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

Glucagon-like Peptide-1 Receptor Agonists: Exciting Avenues Beyond Weight Loss. (PubMed, J Clin Med) - "Leading the list are glucagon-like peptide-1 receptor agonists (GLP1RAs), the first of which, exenatide, was approved by the FDA in 2005...Additionally, on the horizon, the once-weekly basal insulin analog insulin icodec and the once-weekly combination of insulin icodec and semaglutide are expected to be available in the future...It is important that clinicians are familiar with current research in order to provide optimal evidence-based care to patients. In the not-too-distant future, there may be a case to prescribe these drugs for benefits outside diabetes."

Journal • Review • Alzheimer's Disease • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Diabetes • Dyslipidemia • Genetic Disorders • Hepatology • Hypertension • Infertility • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Movement Disorders • Oncology • Parkinson's Disease • Renal Disease • Sexual Disorders • Type 2 Diabetes Mellitus

A Study to Test How a New Long-acting Insulin Works in the Body of Patients With Type 2 Diabetes During Exercise and Prolonged Fasting (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2024 ➔ Apr 2025 | Trial primary completion date: Nov 2024 ➔ Mar 2025

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