Kyinsu (insulin icodec/semaglutide) / Novo Nordisk - LARVOL DELTA

Pharmacokinetic and pharmacodynamic profiles of GZR102, a novel once-weekly fixed-ratio combination of insulin GZR4 and GLP-1 receptor agonist bofanglutide (EASD 2026) - "This contrasts with the PK profile of IcoSema, which exhibited significant drug-drug interactions on C max and T max . The combination of GZR4 and GZR18 in GZR102 did not affect the PK of the individual components compared with mono- component treatments. GZR102 demonstrated greater improvements in glycemic control, body weight reduction, and lipid metabolism compared with mono-component treatments. These findings support the further clinical development of GZR102 as a once-weekly FRC targeting both insulin and GLP-1 receptor pathways simultaneously."

PK/PD data • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Efficacy and hypoglycaemia outcomes with once-weekly IcoSema vs glargine U100 in type 2 diabetes by baseline BMI: COMBINE 4 (EASD 2026) - P3 | "Supported by: Novo Nordisk A/S Clinical Trial Registration Number: NCT06269107 Background and aims: In COMBINE 4, IcoSema (a once-weekly combination of basal insulin icodec and the GLP-1 analogue semaglutide) showed superior glycaemic control and change in body weight, with lower rates of combined clinically significant or severe hypoglycaemia versus insulin glargine U100 in insulin-naive individuals with type 2 diabetes (T2D). In insulin-naïve individuals with T2D, efficacy and hypoglycaemic outcomes with IcoSema versus glargine U100 were overall consistent regardless of baseline BMI."

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

Efficacy and hypoglycaemia outcomes with once-weekly IcoSema vs glargine U100 in type 2 diabetes by baseline HbA1c: COMBINE 4 (EASD 2026) - P3 | "Supported by: Novo Nordisk A/S Clinical Trial Registration Number: NCT06269107 Background and aims: In COMBINE 4, IcoSema (a once-weekly combination of basal insulin icodec and the GLP-1 analogue semaglutide) showed superior glycaemic control and change in body weight, with lower rates of combined clinically significant or severe hypoglycaemia versus insulin glargine U100 in insulin-naive individuals with type 2 diabetes (T2D). In insulin-naïve individuals with T2D, efficacy and hypoglycaemic outcomes with IcoSema versus glargine U100 were overall consistent regardless of baseline HbA 1c ."

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

Cardiometabolic outcomes of once-weekly IcoSema in adults with type 2 diabetes: systematic review and meta-analysis of the COMBINE trials. (PubMed, Cardiovasc Diabetol Endocrinol Rep) - "Once-weekly IcoSema delivers meaningful improvements in weight, blood pressure, and atherogenic lipids, all key modifiable drivers of ASCVD in adults with type 2 diabetes. These surrogate benefits, combined with reduced injection burden and low risk of hypoglycemia, suggest potential for enhanced ASCVD prevention and improved long-term adherence. Results should be interpreted as hypothesis-generating only because only two trials met the inclusion criteria. Dedicated cardiovascular outcome trials are essential to validate these surrogate-marker benefits and to confirm whether they translate into a reduction in cardiovascular events."

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

Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial. (PubMed, Lancet Diabetes Endocrinol) - P3 | "Once-weekly IcoSema demonstrated superior HbA1c reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that IcoSema might be an effective once-weekly treatment option for insulin-naive individuals with type 2 diabetes inadequately controlled on oral glucose-lowering medications."

Journal • P3 data • Cognitive Disorders • Diabetes • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials. (PubMed, Diabetes Obes Metab) - P3 | "Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function."

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

Fangzhou Launches Novo Nordisk’s Once-Weekly Basal Insulin/GLP-1 Therapy in China (GlobeNewswire) - "China is the first market globally to commercialize Kyinsu, making Fangzhou one of the product's key launch partners....The once-weekly therapy combines insulin icodec, the world's first once-weekly basal insulin, with semaglutide, a widely used GLP-1 receptor agonist, to address multiple pathophysiological mechanisms of type 2 diabetes."

Launch non-US • Type 2 Diabetes Mellitus

CGM-derived postprandial glucose with IcoSema versus other insulin regimens: a post hoc analysis of COMBINE 1 and 3. (PubMed, EClinicalMedicine) - P3 | "In the randomised, phase 3a COMBINE 1 and 3 trials, IcoSema (a once-weekly combination therapy of basal insulin icodec [icodec] and semaglutide) was investigated versus icodec (COMBINE 1) or daily BBT (insulin glargine U100 + insulin aspart; COMBINE 3). Future studies that prospectively evaluate CGM-derived PPG outcomes and their clinical relevance across different meal compositions in real-world treatment settings would be beneficial. Novo Nordisk A/S."

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

Improved Treatment Satisfaction with Once-Weekly IcoSema vs. Once-Daily Glargine U100 in Insulin-Naive Adults with Type 2 Diabetes (COMBINE 4) (ADA 2026) - "Introduction and Objective: COMBINE 4 compared the efficacy and safety of IcoSema, a once-weekly combination of insulin icodec + semaglutide, vs once-daily glargine U100 in insulin-naïve adults with T2D. The statistically significantly greater change in DTSQs TTSS in favor of IcoSema vs glargine U100 was driven by improvements in all contributing items."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Hypoglycemia Outcomes with Once-Weekly IcoSema vs. Comparators in T2D by Baseline BMI: COMBINE 1–3 (ADA 2026) - "Introduction and Objective: This post hoc analysis assessed efficacy and hypoglycemia outcomes of IcoSema (a once-weekly combination of insulin icodec + semaglutide) vs comparators (COMBINE 1 [C1]: icodec; COMBINE 2 [C2]: semaglutide 1.0 mg; COMBINE 3 [C3]: basal-bolus therapy) in insulin-experienced (C1+3) or GLP-1 RA experienced (C2) adults with T2D by baseline BMI subgroups. Treatment outcomes were analyzed across baseline BMI subgroups (0.05). Efficacy and hypoglycemia outcomes for IcoSema vs comparators were generally consistent across BMI subgroups."

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

Efficacy and Hypoglycemia Outcomes with Once-Weekly IcoSema vs. Comparators in T2D by Baseline A1C: COMBINE 1–3 (ADA 2026) - "Introduction and Objective: This post hoc analysis assessed efficacy and hypoglycemia outcomes of IcoSema (a once-weekly combination of insulin icodec + semaglutide) vs comparators (COMBINE 1 [C1]: icodec; COMBINE 2 [C2]: semaglutide 1.0 mg; COMBINE 3 [C3]: basal-bolus therapy) in insulin-experienced (C1+3) or GLP-1 RA-experienced (C2) adults with T2D by baseline A1C subgroups. Treatment outcomes were analyzed across baseline A1C subgroups (<8.5% and ≥8.5%) by trial. In C1, a greater treatment difference for change in A1C in favor of IcoSema was seen in the subgroup with baseline A1C ≥8.5% (p value for treatment by subgroup interaction 0.0018). Efficacy and hypoglycemia outcomes for IcoSema vs comparators were generally consistent across A1C subgroups."

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

CGM-Based Metrics in Insulin-Naive Adults with T2D Receiving IcoSema vs. Glargine U100: Post Hoc Analysis of COMBINE 4. (ADA 2026) - "Introduction and Objective: IcoSema is a once-weekly combination therapy of insulin icodec + semaglutide. Compared with glargine U100, IcoSema was associated with improved glycemic control. These findings support IcoSema as a potential once-weekly alternative to daily basal insulin for treatment intensification in insulin-naive adults with T2D."

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

Value and benefit of basic insulin/GLP-1RA weekly preparation in clinical treatment of type 2 diabetes in adults (PubMed, Zhonghua Yi Xue Za Zhi) - "Insulin icodec/semaglutide fixed-ratio combination (IcoSema), the first once-weekly dual-component preparation combining a basal insulin and a GLP-1RA, utilizes advanced formulation technology to achieve stable co-formulation of the ultra-long-acting once-weekly basal insulin and the once-weekly GLP-1RA, with the two components acting in a complementary and synergistic manner. Once-weekly administration helps to simplify the treatment regimen and improve treatment adherence. The clinical application of IcoSema is expected to alleviate the dilemma in Chinese type 2 diabetes management of balancing effective glycemic control with safety and simplicity, offering a new therapeutic option for patients requiring insulin intensification that combines efficacy, safety, and convenience."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • 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

NN1535-8377: A research study to see how weekly IcoSema controls blood sugar levels when compared with daily insulin degludec/insulin aspart (IDegAsp) in people with poorly controlled type 2 diabetes (COMBINE 5) (clinicaltrialsregister.eu) - P2/3 | N=72 | Completed | Sponsor: Novo Nordisk A/S

New P2/3 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Once-Weekly IcoSema Versus Once-Daily IDegLira in People with Type 2 Diabetes: Systematic Literature Review and Network Meta-analysis. (PubMed, Diabetes Ther) - "These results indicate that once-weekly IcoSema is an efficacious treatment option for adults with T2D requiring insulin intensification. IcoSema was associated with improved glycaemic control, weight reduction, and lower hypoglycaemia risk compared with once-daily IDegLira, as well as a reduction in insulin and injection requirements. Weekly IcoSema offers the potential to reduce treatment burden and increase adherence, thereby improving long-term disease control and patient outcomes."

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

Efficacy and safety of once-weekly insulins in type 2 diabetes: A systematic review and meta-analysis. (PubMed, Diabetes Obes Metab) - "OW insulins modestly improve glycaemic control without increasing hypoglycaemia risk, though slight weight gain may occur."

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

A Systematic Literature Review and Network Meta-Analysis of Once-Weekly Icosema With Daily Fixed-Dose Combinations of Basal Insulin and GLP-1 RA in Patients With Type 2 Diabetes After 52 Weeks of Treatment (ISPOR-EU 2025) - "Once-weekly IcoSema was associated with a significantly greater change in HbA1c and body weight after 52 weeks of treatment compared with daily IDegLira, while also demonstrating significantly lower basal insulin dose and level 2 and level 2 or 3 hypoglycaemia rates, in patients with inadequately controlled T2D."

Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • 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 IcoSema in Adults With Type 2 Diabetes: A Systematic Review and Meta-Analysis. (PubMed, AACE Endocrinol Diabetes) - "IcoSema offers better glycemic control and less hypoglycemia risk than controls, with comparable safety for serious AEs. More RCTs involving diverse populations are needed to improve clinical decision-making."

Journal • Retrospective data • Cardiovascular • Diabetes • Hypoglycemia • Infectious Disease • Metabolic Disorders • Pain • Retinal Disorders • Severe Hypoglycemia • 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

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

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

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