IDegLira (insulin degludec/liraglutide) / Novo Nordisk - LARVOL DELTA

A Novel Approach to Managing "Double Diabetes" in a Pediatric Patient on Insulin Pump Therapy: An Off-Label Use of a Fixed-Ratio Insulin Degludec/Liraglutide Combination. (PubMed, Cureus) - "It addressed insulin resistance, improved glycemic control, and mitigated the burdensome cycle of weight gain and escalating insulin doses. This report underscores the need for further research into tailored, multifaceted therapeutic strategies for this growing patient population."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Pediatrics • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Comparative analysis of IDegLira versus insulin glargine in short-term intensive therapy for overweight or obese patients with type 2 diabetes mellitus. (PubMed, Endocrine) - "IDegLira combined with insulin aspart provides superior short-term glycemic control compared with insulin glargine plus insulin aspart in overweight or obese patients with T2DM, with improved glycemic stability, reduced insulin requirements, faster target attainment, and favorable short-term metabolic changes."

Clinical • Journal • Diabetes • Genetic Disorders • Hypoglycemia • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

CER-4-T2D: Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study (clinicaltrials.gov) - P=N/A | N=781430 | Active, not recruiting | Sponsor: Brigham and Women's Hospital | Trial completion date: Jul 2026 ➔ Sep 2027 | Trial primary completion date: Jan 2026 ➔ May 2026

HEOR • Trial completion date • Trial primary completion date • Cardiovascular • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 23-26 October 2023 (European Medicines Agency) - "EMA’s safety committee (PRAC) has concluded that the available evidence does not support a causal association between the Glucagon-Like Peptide-1 Receptor Agonists (GLP-1) - exenatide, liraglutide, dulaglutide, semaglutide, and lixisenatide - and cancer of the thyroid (a small gland in the front and lower part of the neck which makes and releases hormones)....The MAHs for liraglutide- (including Victoza, Saxenda, Xultophy), semaglutide- (including Ozempic, Rybelsus, Wegovy), exenatide- (including Bydureon, Byetta), dulaglutide- (i.e.Trulicity) and lixisenatide- (including Lyxumia, Suliqua) containing products should continue to monitor these events closely, including any new publications, as part of their pharmacovigilance activities and report any new evidence on this issue in their Periodic Safety Update Reports (PSURs)."

European regulatory • Diabetes • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Novo Nordisk’s sales increased by 25% in Danish kroner and by 26% at constant exchange rates to DKK 290.4 billion in 2024 (GlobeNewswire) - "Ozempic sales increased by 26% in both Danish kroner and at CER to DKK 120,342 million...Rybelsus sales increased by 24% measured in Danish kroner and by 26% at CER to DKK 23,301 million...Victoza sales decreased by 37% measured in Danish kroner and by 36% at CER to DKK 5,482 million...Sales of GLP-1 Diabetes care products in the US increased by 24% at CER. The sales increase was mainly driven by continued uptake of Ozempic...Sales of GLP-1 Diabetes care products in EMEA increased by 18% in both Danish kroner and at CER. The sales growth reflects the uptake of Rybelsus and Ozempic, partially offset by lower sales of Victoza...Sales of GLP-1 Diabetes care products in Region China increased by 17% measured in Danish kroner and by 19% at CER. The sales growth mainly reflects the uptake of Ozempic, partially countered by lower sales of Victoza."

Sales • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Transition from Continuous Subcutaneous Insulin Infusion to IDeg-Based Regimens in Hospitalized T2DM Patients: A Single-Center Retrospective Analysis. (PubMed, Diabetes Metab Syndr Obes) - "To evaluate the efficacy, safety, and patient satisfaction of transitioning from CSII to three treatment regimens: insulin degludec (IDeg), insulin degludec/insulin aspart (IDegAsp), or insulin degludec and liraglutide (IDegLira). All three regimens enabled a smooth transition after CSII therapy. IDegAsp and IDegLira demonstrated superior glycemic control and reduced variability compared to IDeg. IDegLira was more convenient and associated with higher patient satisfaction."

Journal • Retrospective data • Diabetes • Fatigue • Hypoglycemia • Metabolic Disorders • Mood Disorders • Psychiatry • Type 2 Diabetes Mellitus

Comparative efficacy and safety of three fixed-ratio combination products in type 2 diabetes: A network meta-analysis. (PubMed, J Diabetes Investig) - "Among the three fixed-ratio combination products, IDegLira appears most effective for glycemic control (in terms of HbA1c and FPG reduction), whereas IDegAsp demonstrates the best safety profile regarding incidence of TEAEs."

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

Improved Glycaemic Control with IDegLira in Chinese Adults with Type 2 Diabetes in Real-World Settings: A Retrospective, Database Cohort Study. (PubMed, Diabetes Ther) - "IDegLira statistically improved glycaemic control by reducing HbA1c, FPG, and PPG levels in the Chinese population with T2D, with a favourable safety profile."

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

IDEGLIRA OR IGLARLIXI GIVEN AFTER SHORT-TERM INTENSIVE INSULIN TREATMENT COMPARED TO BASAL-BOLUS FOR INSULIN-NAIVE TYPE 2 DIABETES PATIENTS WITH SEVERE HYPERGLYCEMIA (ATTD 2026) - "In insulin-naive T2D patients with severe hyperglycemia, FRCs initiated after STII provide similar glucose control as BBT but with less hypoglycemia and a more favorable effect on body weight."

Clinical • Diabetes • Hypoglycemia • 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

Effect of Beta-Cell Function on Glucose Variability When Switching From Insulin Degludec Plus a Dipeptidyl Peptidase-4 Inhibitor to Insulin Degludec/Liraglutide: Preliminary Results From a Pilot Study. (PubMed, Int J Endocrinol) - "Thus, this preliminary result implies that a treatment strategy that includes a glucagon-like peptide-1 receptor agonist might be beneficial for patients being treated with a DPP-4 inhibitor plus basal insulin who show high GV but have preserved beta-cell function. University Hospital Medical Information Network (UMIN) Center Clinical Trials Registry: UMIN 000039460."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

CER-4-T2D: Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study (clinicaltrials.gov) - P=N/A | N=781430 | Active, not recruiting | Sponsor: Brigham and Women's Hospital | Trial completion date: Jul 2024 ➔ Jul 2026 | Trial primary completion date: Jul 2024 ➔ Jan 2026

HEOR • Trial completion date • Trial primary completion date • Cardiovascular • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Switch from premixed insulin analogue to degludec-liraglutide combination: a CGM study. (PubMed, Front Endocrinol (Lausanne)) - "Basal insulin with glucagon-like peptide-1 receptor agonist could be preferred over premixed insulin for intensification in type 2 diabetes due to better glycemic control, lower hypoglycemia risk, and favorable effects on body weight. While numerical reductions in hypoglycemia did not reach statistical significance, treatment was not associated with an increased risk of hypoglycemia. iDegLira can be an efficient and safe treatment option, providing simplified treatment with improved glycemic control."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • 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

Efficacy of IDegLira Combined with Oral Antidiabetic Drugs in Short-Term Intensive Intervention for Remission of Type 2 Diabetes (ChiCTR) - P4 | N=196 | Not yet recruiting | Sponsor: Southern Medical University Southern Hospital; Southern Medical University Southern Hospital

Head-to-Head • New P4 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

IDeglira vs insulin degludec for type 2 diabetes: a systematic review and meta-analysis. (PubMed, Front Endocrinol (Lausanne)) - "Notably, the risk of severe or blood glucose-confirmed symptomatic hypoglycemia, adverse events, and severe adverse events was comparable between IDegLira and insulin degludec. This meta-analysis provides compelling evidence that IDegLira offers superior glycemic control and more favorable effects on body weight compared to insulin degludec, while maintaining a comparable safety profile."

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

Efficacy and Safety of IDegLira in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials. (PubMed, Curr Diabetes Rev) - "IDegLira exhibits a favorable glycemic control effect and acceptable adverse effects in Type 2 Diabetes Mellitus (T2DM). Superior performance in the target glycemic control, particularly suitable for T2DM patients who do not reach the target hemoglobin A1c and have comorbid CVD or obesity."

Clinical • Journal • Retrospective data • Diabetes • Genetic Disorders • Hypoglycemia • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Improved glycaemic control with IDegLira in Chinese adults with type 2 diabetes in a real-world setting: a retrospective cohort study (EASD 2025) - "Supported by Novo Nordisk A/S Clinical Trial Registration Number: N/A Background and aims: IDegLira, a fixed-ratio combination of insulin degludec and liraglutide, is indicated for type 2 diabetes (T2D) treatment. In real-world clinical practice in China, T2D patients on IDegLira showed significant improvements in glycemic control. Reductions in HbA1c were observed across subgroups, with greater reductions in patients who had higher baseline HbA1c levels."

Real-world • Real-world evidence • Retrospective data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Insulin DEgludec/LIraglutide versus multiple daily insulin injections in the transition from hospital to outpatient management assessed by continuous glucose monitoring: the DELI transition trial. (PubMed, Diabetologia) - P3 | "IDegLira proved to be safer and more effective than MDI for individuals with type 2 diabetes who had suboptimal glycaemic control, aiding in their transition from hospital to outpatient care."

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

Practical limitations of complex insulin therapies in type 2 diabetes: Focus on therapy simplification using fixed-ratio combinations of basal insulin and a glucagon-like peptide-1 receptor agonist. (PubMed, Diabetes Obes Metab) - "Current evidence suggests that this approach is equally efficient in terms of glycaemic control with the additional benefit of the reduction of body weight, total daily dose of insulin, and the number of insulin injections administered per day with no increase or reduction of hypoglycaemia. The primary aim of this review is to present the current evidence supporting the simplification of complex insulin regimens in PwT2DM with the two currently available FRCs on the market (insulin glargine 100 U/mL and GLP-1 RA lixisenatide [iGlarLixi] or insulin degludec and GLP-1 RA liraglutide [IDegLira]) and to provide a simple clinical practice-oriented algorithm for clinicians based on the currently available evidence."

Journal • Cardiovascular • Diabetes • Hypoglycemia • 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

What is the 'real-world' experience with fixed-ratio combination therapy (insulin + GLP-1 receptor agonist) in routine clinical practice? Take-home messages for clinicians regarding key outcomes. (PubMed, Diabetes Obes Metab) - "Collectively, these real-world studies confirm that FRCs are effective, safe and patient-centred treatment options for adults with T2D. Their simplified dosing, metabolic benefits and favourable safety profiles support their use for both therapy intensification and de-intensification across a broad spectrum of clinical scenarios. These findings reinforce results from randomized controlled trials, providing further confidence in the role of FRCs in contemporary diabetes care."

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

Switching from insulin injections to degludec/liraglutide in older frail persons: 6-month body composition remodelling. (PubMed, Eur Geriatr Med) - "Switching frail older adults with T2DM to IDegLira improved body composition, metabolic parameters, and reduced insulin needs, filling a critical gap in BIA-based evidence for this population and supporting its use as a safer, simplified alternative to complex insulin regimens."

Journal • Diabetes • Geriatric Disorders • Metabolic Disorders • Sarcopenia • Type 2 Diabetes Mellitus

Choice of Insulin Coformulations: Biphasic Insulin Versus Insulin-GlP1RA. (PubMed, J Pak Med Assoc) - "A comprehensive evaluation,including severity and style of glycaemia, clinical presentation, comorbidities, complications, and culinary preference, allows efficient choice of insulin formulation. This framework helps in initiation,intensification and interchange of injectable therapy,in an apt, and ept, manner."

Journal

Home Medication in the US Based on the Assignment of NDC to ATC Codes (ERA 2025) - "Drug combinations were excluded if a separate ATC code exists in the ATC/DDD Index (e.g., A10AE: insulin degludec/liraglutide)...The mapping provides an initial insight into the use of home medication in the US based on ATC codes. The ATC/DDD Index provides a meaningful combination of drug classes with regard to the area of application. Figure 1 demonstrates the possibility of applying the concept to data based on NDC level."