CLINICAL TRIALS PROFILE FOR LINAGLIPTIN AND METFORMIN HYDROCHLORIDE

All Clinical Trials for Linagliptin And Metformin Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00309608 ↗	Efficacy and Safety of BI 1356 BS (Linagliptin) in Combination With Metformin in Patients With type2 Diabetes	Completed	Boehringer Ingelheim	Phase 2	2006-04-01	The objective of the study is to test the efficacy, safety and tolerability of several doses of BI 1356 BS (1, 5, or 10 mg taken once daily) compared to placebo given for 12 weeks together with metformin in patients with type 2 diabetes mellitus who are not at goal with their HbA1c levels. In addition, there will be an unblinded treatment arm with glimepiride as add-on therapy to metformin for comparison. The influence of several factors (gender, age, weight, race, etc.) on the bioavailability and efficacy of BI 1356 BS will also be tested in this study.
NCT00601250 ↗	Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes	Completed	Boehringer Ingelheim	Phase 3	2008-01-01	The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (5 mg once daily) compared to placebo given for 24 weeks as add-on therapy to metformin in patients with type 2 diabetes mellitus with insufficient glycaemic control
NCT00602472 ↗	BI 1356 (Linagliptin) in Combination With Metformin and a Sulphonylurea in Type 2 Diabetes	Completed	Boehringer Ingelheim	Phase 3	2008-02-01	The objective of the current study is to investigate the efficacy, safety and tolerability of BI 1356 (5 mg once daily) compared to placebo given for 24 weeks as add-on therapy to metformin in combination with a sulphonylurea in patients with type 2 diabetes mellitus with insufficient glycaemic control.
NCT00798161 ↗	Safety and Efficacy of Linagliptin (BI 1356) Plus Metformin in Type 2 Diabetes, Factorial Design	Completed	Boehringer Ingelheim	Phase 3	2008-12-01	The objective of the randomised part of the study is to investigate the efficacy and safety of BI 1356 plus metformin compared to BI 1356 or metformin alone given for 24 weeks to drug naive or previously treated (4 weeks wash-out, 2 weeks placebo run-in) type 2 diabetic patients with insufficient glycaemic control. For the open-label part of the study the objective is to estimate the efficacy and safety of BI 1356 and metformin in type 2 diabetic patients with very poor glycaemic control for 24 weeks
NCT00915772 ↗	Treatment of Type 2 Diabetes With Linagliptin 2.5 mg Bid + Metformin 500 or 1000 mg Bid and Metformin 1000 mg Bid	Completed	Boehringer Ingelheim	Phase 3	2009-06-01	A phase III randomised, double-blind parallel group extension study to investigate the efficacy and safety of twice daily administration of the free combination of linagliptin 2.5 mg + metformin 500 mg or of linagliptin 2.5 mg + metformin 1000 mg versus monotherapy with metformin 1000 mg twice daily over 54 weeks in type 2 diabetic patients previously completing the double-blind part of study 1218.46
NCT00996658 ↗	Linagliptin Versus Placebo in Type 2 Diabetic Patients With Inadequate Glycaemic Control on Metformin in Combination With Pioglitazone	Completed	Eli Lilly and Company	Phase 3	2009-10-01	The objective of the current study is to investigate the efficacy, safety and tolerability of Linagliptin (5 mg once daily) compared to placebo given for 24 weeks as add on therapy to metformin in combination with pioglitazone in patients with type 2 diabetes mellitus with insufficient glycaemic control.

Clinical Trial Conditions for Linagliptin And Metformin Hydrochloride

Condition Name

Condition Name for Linagliptin And Metformin Hydrochloride
Intervention	Trials
Diabetes Mellitus, Type 2	22
Healthy	16
Prediabetic State	4
Insulin Resistance	4

Condition MeSH

Condition MeSH for Linagliptin And Metformin Hydrochloride
Intervention	Trials
Diabetes Mellitus	34
Diabetes Mellitus, Type 2	31
Insulin Resistance	6
Prediabetic State	5

Clinical Trial Locations for Linagliptin And Metformin Hydrochloride

Trials by Country

Trials by Country for Linagliptin And Metformin Hydrochloride
Location	Trials
United States	146
Canada	47
Germany	19
Australia	16
Mexico	12

Trials by US State

Trials by US State for Linagliptin And Metformin Hydrochloride
Location	Trials
Texas	9
Florida	8
California	8
Georgia	8
Ohio	7

Clinical Trial Progress for Linagliptin And Metformin Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Linagliptin And Metformin Hydrochloride
Clinical Trial Phase	Trials
Phase 4	15
Phase 3	18
Phase 2	3

Clinical Trial Status

Clinical Trial Status for Linagliptin And Metformin Hydrochloride
Clinical Trial Phase	Trials
Completed	43
Recruiting	10
Unknown status	7

Clinical Trial Sponsors for Linagliptin And Metformin Hydrochloride

Sponsor Name

Sponsor Name for Linagliptin And Metformin Hydrochloride
Sponsor	Trials
Boehringer Ingelheim	38
Eli Lilly and Company	19
Hospital Regional de Alta Especialidad del Bajio	4

Sponsor Type

Sponsor Type for Linagliptin And Metformin Hydrochloride
Sponsor	Trials
Industry	67
Other	45

Linagliptin and Metformin Hydrochloride: A Comprehensive Review of Clinical Trials, Market Analysis, and Projections

Introduction

Linagliptin and metformin hydrochloride, combined in a single tablet, represent a significant advancement in the management of Type 2 Diabetes Mellitus (T2D). This combination therapy leverages the complementary mechanisms of action of linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin, a biguanide, to enhance glycemic control. Here, we delve into the clinical trials, market analysis, and future projections for this drug combination.

Mechanism of Action

Linagliptin works by increasing the levels of incretin hormones, which in turn enhance insulin secretion and reduce glucagon levels, thereby regulating blood glucose levels. Metformin, on the other hand, decreases hepatic glucose production and increases insulin sensitivity, further contributing to improved glycemic control[2].

Clinical Trials

Efficacy and Safety

Several clinical trials have demonstrated the efficacy and safety of the combination of linagliptin and metformin. A 24-week, randomized, double-blind study showed that the combination of linagliptin (5 mg/day) and metformin (1500-2000 mg/day) significantly reduced A1C levels by 2.9% compared to linagliptin alone, which reduced A1C by 2.0%. This combination also led to a greater reduction in fasting plasma glucose (FPG) levels and a higher percentage of patients achieving an A1C less than 7%[1].

In another study, the combination of linagliptin 2.5 mg twice daily and metformin 500 or 1000 mg twice daily resulted in A1C reductions of 1.3% and 1.7%, respectively, which were greater than the reductions seen with monotherapy. This combination was also well-tolerated with low rates of hypoglycemia and adverse events comparable to placebo[5].

Bioequivalence and Dose-Response

Clinical trials have established the bioequivalence of the combination tablet to the separate administration of linagliptin and metformin. A 12-week trial demonstrated no additional reduction in HbA1c with an increase in linagliptin dose from 5 mg to 10 mg when co-administered with metformin, indicating that the 5 mg dose is sufficient for optimal efficacy[3].

Triple Combination Therapy

Studies have also explored the efficacy of adding empagliflozin, an SGLT2 inhibitor, to the combination of linagliptin and metformin. These trials showed that the triple fixed-dose combination (FDC) of empagliflozin, linagliptin, and metformin significantly reduced mean HbA1c levels and was well-tolerated, with no new safety concerns raised[4].

Market Analysis

Market Drivers

The market for linagliptin and metformin hydrochloride tablets is driven by several key factors:

• Rising Prevalence of Diabetes: The increasing global incidence of T2D creates a growing demand for effective diabetes management solutions.
• Healthcare Sector Advancements: Improvements in healthcare infrastructure and access to medications contribute to market growth.
• Preference for Combination Therapies: Combination therapies like linagliptin and metformin enhance patient compliance and glycemic control, making them more appealing to both patients and healthcare providers[2].

Market Restraints

Despite the positive drivers, the market faces several challenges:

• Potential Side Effects: Anticipated side effects and safety concerns associated with the combination therapy can impede market expansion.
• Regulatory Hurdles: Stringent approval processes and regulatory requirements can slow down the introduction of new products.
• Price Sensitivity: In emerging economies, price sensitivity and the availability of alternative treatments can pose significant challenges[2].

Competitive Landscape

The competitive landscape for linagliptin and metformin hydrochloride tablets is characterized by:

• Market Penetration: Detailed data from key industry players indicate a strong presence in the market.
• Market Development: Opportunities for growth exist in both emerging and mature segments, with potential for expansion into untapped geographic regions.
• Product Development & Innovation: Ongoing research and development efforts focus on improving product innovation and manufacturing capabilities[2].

Market Projections

Growth Prospects

The market for linagliptin and metformin hydrochloride tablets is expected to grow significantly due to the increasing demand for effective diabetes management solutions. The global diabetes market is projected to expand, driven by the rising prevalence of T2D and advancements in healthcare.

Emerging Markets

Emerging markets offer substantial growth opportunities, although they also present challenges such as price sensitivity and regulatory hurdles. Strategic investments and partnerships can help navigate these challenges and capitalize on the growing demand in these regions[2].

Geriatric Populations

The potential for linagliptin and metformin in geriatric populations is significant, given the higher prevalence of T2D in older adults. Combination therapies are particularly beneficial for this demographic due to their simplicity and enhanced compliance[2].

Key Takeaways

• Clinical Efficacy: The combination of linagliptin and metformin has been shown to significantly improve glycemic control in patients with T2D.
• Market Growth: The market is driven by the rising prevalence of diabetes, healthcare advancements, and a preference for combination therapies.
• Challenges: Potential side effects, regulatory hurdles, and price sensitivity in emerging economies are key challenges.
• Future Prospects: The market is expected to grow, with opportunities in emerging markets and geriatric populations.

FAQs

Q: What is the mechanism of action of linagliptin and metformin hydrochloride?

A: Linagliptin increases incretin levels, enhancing insulin secretion and reducing glucagon levels, while metformin decreases hepatic glucose production and increases insulin sensitivity.

Q: What are the key findings from clinical trials of linagliptin and metformin?

A: Clinical trials have shown that the combination significantly reduces A1C levels, FPG levels, and results in a higher percentage of patients achieving an A1C less than 7%.

Q: What are the market drivers for linagliptin and metformin hydrochloride tablets?

A: The market is driven by the rising prevalence of diabetes, healthcare sector advancements, and a preference for combination therapies.

Q: What are the main challenges facing the market for linagliptin and metformin hydrochloride tablets?

A: The main challenges include potential side effects, regulatory hurdles, and price sensitivity in emerging economies.

Q: What are the future growth prospects for linagliptin and metformin hydrochloride tablets?

A: The market is expected to grow, with significant opportunities in emerging markets and geriatric populations.

Sources

1. Eli Lilly and Company. Type 2 diabetes: Jentadueto® (linagliptin and metformin).
2. 360iResearch. Linagliptin & Metformin Hydrochloride Tablets Market.
3. FDA. 201280Orig1s000 ClinPharmR.pdf.
4. Tandfonline. Triple fixed-dose combination empagliflozin, linagliptin, and metformin XR FDC tablets.
5. Eli Lilly and Company. New Phase III Data and Pooled Analysis for Linagliptin Show Improved Glycemic Control.