LAI287/semaglutide (NN1535) / Novo Nordisk - LARVOL DELTA

CGM-Based Outcomes in Adults with T2D Receiving IcoSema vs. Comparators—Post Hoc Analysis of COMBINE 1 and 3 (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

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

A1C and Hypoglycemia Outcomes with Once-Weekly IcoSema vs. Comparators in T2D by Kidney Function (ADA 2025) - "Available on Friday, June 13, 2025 at 08:00am CDT."

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) - "Available on Friday, June 13, 2025 at 08:00am CDT."

Retrospective data • Metabolic Disorders

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

IcoSema as an alternative to basal bolus treatment (COMBINE 3) (EASD 2024) - "There is no abstract associated with this presentation."

Metabolic Disorders

Intensification with IcoSema in a GLP-1RA experienced population (COMBINE 2) (EASD 2024) - "There is no abstract associated with this presentation."

Clinical • Metabolic Disorders

Basal insulin intensification by switching to once weekly IcoSema (COMBINE 1) (EASD 2024) - "There is no abstract associated with this presentation."

Metabolic Disorders

IcoSema: unveiling the future of diabetes management from a clinical pharmacology perspective. (PubMed, J Basic Clin Physiol Pharmacol) - "IcoSema, a groundbreaking approach to diabetes management, combines insulin icodec and semaglutide to offer a transformative treatment option...This comprehensive article evaluates the potential of IcoSema from a clinical pharmacology perspective, examining the pharmacokinetics, efficacy, safety, compliance and cost-effectiveness of its individual components, as well as considering comparable combination therapies like iGlarLixi and IDegLira...Ongoing trials investigating IcoSema are expected to provide valuable insights into its efficacy, safety and comparative effectiveness. By addressing concerns such as potential side effects, individual patient response and drug interactions, healthcare providers can optimize treatment outcomes and enhance the management of type 2 diabetes."

Journal • Review • Diabetes • Infectious Disease • Metabolic Disorders • Type 2 Diabetes Mellitus

COMBINE 1: A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Weekly Insulin Icodec (clinicaltrials.gov) - P3 | N=1291 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion • Diabetes • Metabolic Disorders • 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=474 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • 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=474 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Weekly Semaglutide (COMBINE 2) (clinicaltrials.gov) - P3 | N=683 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

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

COMBINE 3 phase 3a trial successfully completed with once-weekly IcoSema demonstrating non-inferior reduction in HbA1c versus daily basal-bolus treatment (insulin glargine U100 and insulin aspart) in people with type 2 diabetes (Novo Nordisk Press Release) - P3a | N=679 | COMBINE 3 (NCT05013229) | Sponsor: Novo Nordisk A/S | "Novo Nordisk today announced topline results from the COMBINE 3 phase 3a trial of once-weekly IcoSema, a fixed-ratio combination of basal insulin icodec and semaglutide....The trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 52 with once-weekly IcoSema compared with insulin glargine U100 and insulin aspart....From an overall baseline HbA1c of 8.30%, once-weekly IcoSema achieved an estimated reduction in HbA1c of -1.47 percentage points compared with -1.40 percentage points for insulin glargine U100 and insulin aspart (estimated treatment difference: –0.06 percentage points)....COMBINE 3 is the first trial to readout in the phase 3a COMBINE programme, and results from COMBINE 1 and COMBINE 2 will be shared later this year."

P3 data • P3 data: top line • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Novel Alzheimer’s Trials Evaluate Senolytics, Semaglutide, CRISPR, and More (MedPageToday) - "'In 2023, the Alzheimer's drug development pipeline had 187 trials, the highest number on record, according to Jeffrey Cummings...Metformin and semaglutide [Ozempic], effective drugs against type 2 diabetes, are ideal candidates for repurposing to address the metabolic dysfunction in [Alzheimer's disease],' Fillit and co-authors wrote....'We envision a future where multiple treatments address every aspect of this most complex disease,' Carrillo noted. 'And that, once proven, the treatments can be combined in ways that complement and enhance each other to reduce risk, treat effectively, stop the progression, and eventually cure Alzheimer's disease and all other dementia.'"

Media quote

A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3) (clinicaltrials.gov) - P3 | N=679 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

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

A Research Study to Look at How Insulin Icodec and Semaglutide Work in the Body of People From China With Type 2 Diabetes When Given Alone or Together (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Novo Nordisk A/S | Recruiting ➔ Completed | Trial completion date: Jul 2023 ➔ Apr 2023 | Trial primary completion date: Jul 2023 ➔ Apr 2023

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

Understanding the Impact of Weight Loss Drugs on the Brain: Ozempic and the Changing Landscape of Obesity Treatment - "New drugs have upended some long-held assumptions about weight and health. 'What these drugs have proven is that patients are right: it’s not their fault,' said Dr. Louis Aronne..."

Media quote

A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Weekly Semaglutide (COMBINE 2) (clinicaltrials.gov) - P3 | N=680 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

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

COMBINE 1: A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Weekly Insulin Icodec (clinicaltrials.gov) - P3 | N=1290 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

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

A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3) (clinicaltrials.gov) - P3 | N=680 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting

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