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

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

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

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

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

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

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

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

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

IcoSema and the evolution of fixed-ratio insulin-GLP-1 receptor agonist therapies. (PubMed, Lancet Diabetes Endocrinol) - No abstract available

Journal

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

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

Glucose-Lowering Agents Developed in the Last Two Decades and Their Perioperative Implications. (PubMed, Pharmaceuticals (Basel)) - "There have been other developments as well. For instance, Imeglimin, a variant of metformin available in Japan and India, Icodec, a once-weekly basal insulin formulation, and IcoSema, a once-weekly combination of Icodec plus semaglutide, are all being explored, although in their early stages or facing approval challenges."

Journal • Review • Anesthesia • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Metabolic Disorders • Obesity

Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial. (PubMed, Diabetologia) - P3 | "In people living with type 2 diabetes inadequately managed with GLP-1 RA therapy, with or without additional oral glucose-lowering medications, switching to once-weekly IcoSema in comparison with once-weekly semaglutide 1.0 mg demonstrated superiority in HbA1c reduction, similar rates of clinically significant or severe hypoglycaemia, and similar frequency of gastrointestinal adverse events. However, weight change from baseline to week 52 was statistically significantly in favour of semaglutide 1.0 mg."

Journal • Alzheimer's Disease • Cognitive Disorders • Diabetes • Gastrointestinal Disorder • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Evaluating semaglutide + LAI-287 (IcoSema) for the treatment of diabetes mellitus type II. (PubMed, Expert Opin Pharmacother) - "The key trials from the clinical development process of insulin icodec, semaglutide, and IcoSema are reviewed with important endpoints highlighted. Once-weekly IcoSema offers glycemic efficacy that is non-inferior to glargine+aspart, similar risk of hypoglycemia, significant reduction in body weight, the convenience of use, and favorable safety profile with most adverse events being gastrointestinal."

Journal • Review • Diabetes • Gastrointestinal Disorder • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus. (PubMed, Clin Drug Investig) - P1 | "The combination of icodec and semaglutide in IcoSema leads to a higher and earlier maximum semaglutide concentration, which will guide the dose recommendations for IcoSema."

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

IcoSema's leap forward: new data from COMBINE 3 paves the way. (PubMed, J Basic Clin Physiol Pharmacol) - No abstract available

Journal

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=474 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

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