CLINICAL TRIALS PROFILE FOR INSULIN DEGLUDEC; LIRAGLUTIDE

All Clinical Trials for Insulin Degludec; Liraglutide

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01319240 ↗	Safety and Tolerability of Insulin Degludec/Liraglutide (A3) in Healthy Subjects	Completed	Novo Nordisk A/S	Phase 1	2011-03-01	This trial is conducted in Europe. The aim of this trial is to compare the bioavailability of insulin degludec and liraglutide, when administered either combined or as separate administrations.
NCT01336023 ↗	Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Subjects With Type 2 Diabetes	Completed	Novo Nordisk A/S	Phase 3	2011-05-23	This trial is conducted globally. The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin degludec (IDeg) and liraglutide (Lira) in subjects with type 2 diabetes. Subjects are to continue their pre-trial treatment with metformin or metformin + pioglitazone throughout the entire trial.
NCT01388361 ↗	Comparison of the Efficacy and Safety of Two Intensification Strategies in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin	Completed	Novo Nordisk A/S	Phase 3	2011-09-01	This trial is conducted in Europe and North America. The aim of this trial is to compare the efficacy and safety of adding liraglutide versus addition of insulin aspart with the largest meal to insulin degludec in subjects with type 2 diabetes. Eligible subjects with an HbA1c equal to or above 7% at end of treatment in NN1250-3643 (NCT01193309) trial will be randomised to receive treatment intensification while subjects with an HbA1c below 7% at end of treatment in NN1250-3643 (NCT01193309) may continue to receive insulin degludec treatment. Subjects are to continue their pre-trial metformin treatment.
NCT01392573 ↗	A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec in Subjects With Type 2 Diabetes	Completed	Novo Nordisk A/S	Phase 3	2011-11-28	This trial is conducted in Asia, Europe and the United States of America (USA). The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide (IDegLira) and insulin degludec (IDeg) in subjects with type 2 diabetes. Subjects continue their pre-trial treatment with metformin throughout the entire trial.
NCT01618162 ↗	The Efficacy of Insulin Degludec/Liraglutide as add-on Therapy in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on Sulphonylurea With or Without Metformin Therapy	Completed	Novo Nordisk A/S	Phase 3	2012-08-29	This trial is conducted in Asia, Europe and the United States of America (USA). The aim of this trial is to investigate the efficacy and safety of insulin degludec/liraglutide in insulin naïve subjects inadequately controlled with SU (sulphonylurea) alone or in combination with metformin. All subjects will continue their pre-trial SU treatment with or without metformin treatment without changing the frequency or dose throughout the trial.
NCT01664247 ↗	The Effect of Insulin Degludec in Combination With Liraglutide and Metformin in Subjects With Type 2 Diabetes Qualifying for Treatment Intensification	Completed	Novo Nordisk A/S	Phase 3	2012-10-01	This trial is conducted in Africa, Asia, Europe and North America. The purpose of the trial is to investigate the effect of insulin degludec (IDeg) in combination with liraglutide (Lira) and metformin (at least 1500 mg daily or maximum tolerated dose) in subjects with type 2 diabetes qualifying for treatment intensification.
NCT01676116 ↗	The Efficacy of Insulin Degludec/Liraglutide in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and OAD Therapy	Completed	Novo Nordisk A/S	Phase 3	2012-08-29	This trial is conducted in Europe, Oceania and the United States of America (USA). The aim of the trial is to investigate the efficacy of insulin degludec/liraglutide in controlling glycaemia in adults with type 2 diabetes inadequately controlled on glucagon-like peptide-1 (GLP-1) receptor agonist and OAD therapy.

Clinical Trial Conditions for Insulin Degludec; Liraglutide

Condition Name

Condition Name for Insulin Degludec; Liraglutide
Intervention	Trials
Diabetes	20
Diabetes Mellitus, Type 2	19
Healthy	2
Type 2 Diabetes	1

Condition MeSH

Condition MeSH for Insulin Degludec; Liraglutide
Intervention	Trials
Diabetes Mellitus, Type 2	23
Diabetes Mellitus	22
Hypoglycemia	1

Clinical Trial Locations for Insulin Degludec; Liraglutide

Trials by Country

Trials by Country for Insulin Degludec; Liraglutide
Location	Trials
United States	248
China	39
India	38
Canada	29
South Africa	22

Trials by US State

Trials by US State for Insulin Degludec; Liraglutide
Location	Trials
California	12
Florida	12
Texas	11
Tennessee	11
Pennsylvania	11

Clinical Trial Progress for Insulin Degludec; Liraglutide

Clinical Trial Phase

Clinical Trial Phase for Insulin Degludec; Liraglutide
Clinical Trial Phase	Trials
Phase 3	19
Phase 1	3
N/A	2

Clinical Trial Status

Clinical Trial Status for Insulin Degludec; Liraglutide
Clinical Trial Phase	Trials
Completed	21
Recruiting	4

Clinical Trial Sponsors for Insulin Degludec; Liraglutide

Sponsor Name

Sponsor Name for Insulin Degludec; Liraglutide
Sponsor	Trials
Novo Nordisk A/S	21
Emory University	1
Stefano Rizza	1

Sponsor Type

Sponsor Type for Insulin Degludec; Liraglutide
Sponsor	Trials
Industry	21
Other	5

Insulin Degludec and Liraglutide: Clinical Trials, Market Analysis, and Projections

Introduction

Insulin degludec and liraglutide, when combined as IDegLira, represent a significant advancement in the treatment of type 2 diabetes. This combination therapy brings together the benefits of long-acting basal insulin and a glucagon-like peptide-1 receptor agonist (GLP-1RA), offering improved glycemic control, reduced risk of hypoglycemia, and weight neutrality. Here, we delve into the recent clinical trials, market analysis, and future projections for this drug combination.

Clinical Trials Overview

Phase 3 Clinical Trials

The Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes (DUAL) phase III clinical trial program has been instrumental in establishing the efficacy and safety of IDegLira. These trials compared IDegLira with basal insulin, GLP-1RAs, and basal-bolus therapy, demonstrating superior glycated hemoglobin (HbA1c) reductions and lower rates of hypoglycemia and weight gain[2].

A notable trial compared IDegLira with insulin glargine in patients with uncontrolled type 2 diabetes. The results showed that IDegLira was not only noninferior but also statistically superior to glargine in reducing HbA1c levels, with a greater reduction of -1.81% versus -1.13% for glargine. Additionally, IDegLira resulted in less weight gain and fewer hypoglycemic episodes[4].

In-Silico Simulations

Recent studies have also utilized in-silico models to replicate clinical trial findings. The UVLab platform, using 6062 virtual subjects with type 2 diabetes, successfully replicated the outcomes of a 26-week phase 3 clinical trial, validating the predictive capability of these models for treatment planning and clinical trial enhancement[1].

Mechanism of Action

Insulin Degludec

Insulin degludec is an ultra-long-acting basal insulin analog with a plasma half-life of 13 hours. It forms soluble multi-hexamers upon subcutaneous injection, creating a depot that allows for continuous and slow absorption. This mechanism ensures a stable and prolonged insulin action, mimicking the natural insulin profile[3][5].

Liraglutide

Liraglutide is a GLP-1RA that activates the GLP-1 receptor, increasing intracellular cyclic AMP and leading to insulin release in the presence of elevated glucose concentrations. It also enhances insulin synthesis and secretion, delays gastric emptying, and reduces food intake, contributing to a slower rise in plasma glucose after meals[3].

Market Analysis

Physician Satisfaction and Patient Outcomes

Physicians' real-world experience with IDegLira has been highly positive. A multicountry European survey revealed that physicians are satisfied with IDegLira, citing its ability to help patients achieve HbA1c targets quickly, reduce the number of injections, and avoid weight gain. Approximately 76% of patients achieved their HbA1c targets within six months, and physicians reported higher patient motivation with IDegLira compared to basal-bolus therapy[2].

Market Penetration

IDegLira has been gaining traction in the diabetes treatment market due to its unique benefits. The combination therapy addresses clinical inertia by offering a pragmatic titration algorithm, low rates of hypoglycemia, and weight neutrality, making it an attractive option for both physicians and patients. The drug's once-daily administration and fixed-ratio combination simplify treatment regimens, which is a significant factor in patient compliance and market adoption[2].

Safety and Adverse Effects

Hypoglycemia and Weight Gain

Clinical trials have consistently shown that IDegLira results in lower rates of hypoglycemia compared to traditional basal insulin therapies. Additionally, IDegLira is associated with weight neutrality or even weight loss, which is a significant advantage over many other insulin therapies that often lead to weight gain[2][4].

Gastrointestinal Side Effects

Liraglutide, as a GLP-1RA, can cause gastrointestinal side effects such as nausea, which was reported by between 14% and 40% of patients in clinical trials. However, these side effects are generally transient and manageable[4].

Pregnancy and Lactation

The use of IDegLira in pregnancy and lactation requires careful consideration. Animal studies have shown potential teratogenic effects with liraglutide, although human data are limited. Both insulin degludec and liraglutide have been found in the milk of lactating rats, but the clinical significance of this is not fully understood[3].

Market Projections

Growing Demand

The global diabetes market is expected to grow significantly due to the increasing prevalence of type 2 diabetes. IDegLira, with its unique combination of benefits, is poised to capture a substantial share of this market. The simplicity of its once-daily administration and the favorable safety profile are likely to drive adoption among both patients and healthcare providers.

Competitive Landscape

IDegLira competes in a crowded market with other basal insulins and GLP-1RAs. However, its fixed-ratio combination and the comprehensive data from the DUAL trial program position it as a strong contender. As more physicians and patients become aware of its benefits, IDegLira is expected to gain further market traction.

Regulatory Environment

Regulatory approvals and ongoing monitoring by health authorities will continue to play a crucial role in the market success of IDegLira. The drug has already received approvals in several countries, and ongoing pharmacovigilance will help in addressing any emerging safety concerns and reinforcing its market position[3][5].

Key Takeaways

• Clinical Efficacy: IDegLira has demonstrated superior glycemic control, reduced hypoglycemia, and weight neutrality in clinical trials.
• Physician Satisfaction: Physicians report high satisfaction with IDegLira due to its ease of use, effectiveness, and patient compliance.
• Market Growth: The growing demand for diabetes treatments and the unique benefits of IDegLira position it for significant market growth.
• Safety Profile: IDegLira has a favorable safety profile with lower rates of hypoglycemia and weight gain, though gastrointestinal side effects and pregnancy/lactation considerations need to be monitored.

FAQs

What is IDegLira, and how does it work?

IDegLira is a fixed-ratio combination of insulin degludec (a long-acting basal insulin) and liraglutide (a GLP-1RA). It works by providing a stable insulin action and enhancing insulin release and secretion in response to elevated glucose levels.

What are the key benefits of IDegLira over other diabetes treatments?

IDegLira offers improved glycemic control, reduced risk of hypoglycemia, weight neutrality, and a simplified once-daily administration regimen.

How does IDegLira compare to basal-bolus therapy?

IDegLira has been shown to be more effective in achieving HbA1c targets, reducing the number of injections, and avoiding weight gain compared to basal-bolus therapy.

What are the common side effects of IDegLira?

Common side effects include gastrointestinal issues such as nausea, though these are generally transient. Hypoglycemia is less common compared to other insulin therapies.

Is IDegLira safe for use during pregnancy and lactation?

The use of IDegLira in pregnancy and lactation requires careful consideration due to potential teratogenic effects and the presence of the drugs in breast milk, although human data are limited.

Sources

1. In-Silico Replay of Insulin Degludec and Liraglutide Clinical Trials. Diabetes, 73(Supplement 1), 75-OR.
2. Physicians' real-world experience with IDegLira: results of a multicountry, European online survey. BMJ Open Diabetes Research & Care, 6(1), e000531.
3. Human Factors Study Protocol Review for Insulin Degludec and Liraglutide Injection. FDA, CDER, OSE, DMEPA.
4. Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin in Patients With Uncontrolled Type 2 Diabetes. JAMA, 315(9), 898-907.
5. Australian Public Assessment Report for insulin degludec/liraglutide. TGA.