CLINICAL TRIALS PROFILE FOR DAPAGLIFLOZIN; METFORMIN HYDROCHLORIDE; SAXAGLIPTIN HYDROCHLORIDE

All Clinical Trials for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01606007 ↗	Safety and Efficacy of Combination Saxagliptin & Dapagliflozin Added to Metformin to Treat Subjects With Type 2 Diabetes	Completed	AstraZeneca	Phase 3	2012-07-01	The purpose of this study is to learn if a combination of BMS-477118 (Saxagliptin) and BMS -512148 (Dapagliflozin) added to Metformin can improve (decrease) Glycosylated Hemoglobin (Hemoglobin A1c) in patients with type 2 diabetes after 24 weeks of treatment. The safety of this treatment will also be studied.
NCT01619059 ↗	Safety and Efficacy of Saxagliptin in Triple Therapy to Treat Subjects With Type 2 Diabetes	Completed	AstraZeneca	Phase 3	2012-06-01	The purpose of this study is to learn if BMS-477118 (Saxagliptin) as part of a triple combination therapy can improve (decrease) hemoglobin A1c in patients with type 2 diabetes after 24 weeks of treatment compared to a 2 drug oral antidiabetic therapy. The safety of this treatment will also be studied.
NCT01646320 ↗	Safety and Efficacy of Dapagliflozin in Triple Therapy to Treat Subjects With Type 2 Diabetes	Completed	AstraZeneca	Phase 3	2012-09-01	The purpose of this study is to learn if BMS-512148 (Dapagliflozin) as part of a triple combination therapy can improve (decrease) hemoglobin A1c in patients with type 2 diabetes after 24 weeks of treatment compared to a 2 drug oral antidiabetic therapy. The safety of this treatment will also be studied.
NCT02284893 ↗	Study to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Sitagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Contr	Completed	AstraZeneca	Phase 3	2014-09-09	Study will evaluate if a combination of saxagliptin and dapagliflozin added concurrently to metformin in combination with diet and exercise is superior to sitagliptin added to metformin in combination with diet and exercise in reducing mean HbA1c over a treatment period of 26 weeks.

Clinical Trial Conditions for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride

Condition Name

Condition Name for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride
Intervention	Trials
Type 2 Diabetes Mellitus	7
Type 2 Diabetes	4
Type2 Diabetes Mellitus	4
Diabetes Mellitus, Type 2	4

Condition MeSH

Condition MeSH for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride
Intervention	Trials
Diabetes Mellitus, Type 2	18
Diabetes Mellitus	18
Prediabetic State	1
Glucose Intolerance	1

Clinical Trial Locations for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride

Trials by Country

Trials by Country for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride
Location	Trials
United States	130
Canada	18
Mexico	17
Romania	9
United Kingdom	8

Trials by US State

Trials by US State for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride
Location	Trials
Texas	10
Florida	8
California	8
Arizona	6
Tennessee	6

Clinical Trial Progress for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride
Clinical Trial Phase	Trials
Phase 4	4
Phase 3	10
Phase 2	1

Clinical Trial Status

Clinical Trial Status for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride
Clinical Trial Phase	Trials
Completed	12
Recruiting	4
Unknown status	2

Clinical Trial Sponsors for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride

Sponsor Name

Sponsor Name for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride
Sponsor	Trials
AstraZeneca	15
The University of Texas Health Science Center at San Antonio	2
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	1

Sponsor Type

Sponsor Type for Dapagliflozin; Metformin Hydrochloride; Saxagliptin Hydrochloride
Sponsor	Trials
Industry	17
Other	16
NIH	1

Dapagliflozin, Metformin Hydrochloride, and Saxagliptin Hydrochloride: Clinical Trials, Market Analysis, and Projections

Introduction

The combination of dapagliflozin, metformin hydrochloride, and saxagliptin hydrochloride is a significant advancement in the treatment of type 2 diabetes mellitus (T2DM). This article provides an update on the clinical trials, market analysis, and future projections for this triple therapy.

Clinical Trials Update

Phase III Trials

A key Phase III trial (D1683C00005) conducted by AstraZeneca aimed to evaluate the safety and efficacy of saxagliptin 5mg co-administered with dapagliflozin 5mg, compared to each drug alone, all as add-on therapy to metformin in patients with T2DM who had inadequate glycemic control on metformin alone. This multi-center, randomized, double-blind, active-controlled trial involved 905 patients and was verified in September 2018[1].

Efficacy and Safety

The trial assessed the combination's impact on hemoglobin A1c (HbA1c) levels, as well as its safety profile. The results indicated that the combination of dapagliflozin and saxagliptin with metformin was effective in reducing HbA1c levels compared to monotherapy with either dapagliflozin or saxagliptin[1].

Pediatric Studies

Another significant study focused on pediatric patients aged 10 to less than 18 years with T2DM. This Phase 3 trial evaluated the safety, efficacy, and pharmacokinetics of dapagliflozin and saxagliptin, with or without metformin and/or insulin. The study aimed to determine the efficacy of these drugs in achieving a glycemic target of HbA1c <7% and assessed their impact on growth, maturity, and bone health[4].

Mechanism of Action

Dapagliflozin

Dapagliflozin works by inhibiting the sodium-glucose cotransporter 2 (SGLT2) in the kidneys, preventing the reabsorption of glucose and thereby reducing blood sugar levels[3].

Saxagliptin

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that helps control blood sugar levels by increasing the release of insulin from the pancreas and decreasing the production of glucose by the liver[3].

Metformin Hydrochloride

Metformin reduces the absorption of sugar from the stomach, decreases the release of stored sugar from the liver, and enhances the body's use of insulin, making it more effective at lowering blood sugar levels[3].

Market Analysis

Cost-Effectiveness

A cost-utility analysis compared the long-term cost-effectiveness of dapagliflozin and saxagliptin, both separately and together, in patients with T2DM inadequately controlled by metformin. The study used the UKPDS OM2 model to project lifetime disease progression and therapy effectiveness. The results suggested that the combination therapy could offer better cost-effectiveness compared to monotherapy, particularly in reducing long-term complications associated with T2DM[2].

Market Demand

The demand for effective T2DM treatments is high and growing due to the increasing prevalence of diabetes worldwide. The combination of dapagliflozin, metformin, and saxagliptin addresses a significant need for therapies that can be used in various stages of the disease, making it a promising product in the diabetes market.

Regulatory Approvals

FDA Approval

AstraZeneca submitted a New Drug Application (NDA) for the triple combination product (dapagliflozin/saxagliptin/metformin) under the 505(b)(1) pathway. The FDA reviewed the clinical pharmacology data, including a Phase 1 comparative pharmacokinetic study, and evaluated the safety and efficacy of the combination in various dosages[5].

Pharmacokinetics

Combination Therapy

The pharmacokinetic study (D168AC00001) compared the systemic exposure of dapagliflozin, saxagliptin, and metformin when administered as a single oral dose of the triple combination product versus the monocomponents. The results showed that the combination product had similar pharmacokinetic parameters to the monocomponents, indicating that the combination does not significantly alter the absorption or metabolism of the individual drugs[5].

Future Projections

Market Growth

The diabetes market is expected to grow significantly due to the increasing prevalence of T2DM and the need for effective treatments. The combination of dapagliflozin, metformin, and saxagliptin is poised to capture a substantial share of this market due to its efficacy and safety profile.

Competitive Landscape

The competitive landscape in the T2DM treatment market is robust, with several other combination therapies available. However, the unique mechanism of action of dapagliflozin, combined with the established efficacy of saxagliptin and metformin, positions this triple therapy as a strong competitor.

Patient Compliance

The convenience of a single tablet containing all three active ingredients is expected to improve patient compliance, as it simplifies the treatment regimen and reduces the number of pills patients need to take daily.

Key Takeaways

• Clinical Efficacy: The combination of dapagliflozin, saxagliptin, and metformin has shown significant efficacy in reducing HbA1c levels and improving glycemic control.
• Cost-Effectiveness: Long-term cost-utility analyses suggest that this combination therapy can be more cost-effective than monotherapy.
• Regulatory Approval: The FDA has reviewed and approved the clinical pharmacology data for this triple combination product.
• Market Potential: The growing demand for effective T2DM treatments positions this combination therapy for significant market growth.
• Patient Compliance: The single-tablet formulation is expected to enhance patient compliance.

FAQs

Q: What is the primary mechanism of action of dapagliflozin in treating type 2 diabetes?

A: Dapagliflozin works by inhibiting the sodium-glucose cotransporter 2 (SGLT2) in the kidneys, preventing the reabsorption of glucose and thereby reducing blood sugar levels[3].

Q: How does saxagliptin contribute to blood sugar control?

A: Saxagliptin is a DPP-4 inhibitor that increases the release of insulin from the pancreas and decreases the production of glucose by the liver[3].

Q: What is the role of metformin in the combination therapy?

A: Metformin reduces the absorption of sugar from the stomach, decreases the release of stored sugar from the liver, and enhances the body's use of insulin[3].

Q: Has the FDA approved the combination of dapagliflozin, saxagliptin, and metformin?

A: Yes, the FDA has reviewed and approved the clinical pharmacology data for this triple combination product under the 505(b)(1) pathway[5].

Q: What are the potential benefits of using a single-tablet combination of these drugs?

A: The single-tablet formulation simplifies the treatment regimen, potentially improving patient compliance, and offers a convenient option for managing type 2 diabetes[5].

Sources

1. AstraZeneca Clinical Trials: "A Multi-Center, Randomized, Double-Blind, Phase III Trial to Evaluate the Safety and Efficacy of Saxagliptin 5mg Co-administered with Dapagliflozin 5mg compared to Saxagliptin 5mg or Dapagliflozin 5mg all given as Add-on Therapy to Metformin in Patients with Type 2 Diabetes who have Inadequate Glycaemic Control on Metformin Alone."
2. PubMed: "Cost-Utility Analysis of Dapagliflozin Versus Saxagliptin Treatment in Patients with Type 2 Diabetes Mellitus Inadequately Controlled by Metformin."
3. Mayo Clinic: "Dapagliflozin, Saxagliptin, and Metformin (oral route) - Description."
4. FDA: "dapagliflozin WR reissue - FDA."
5. FDA: "Clinical Pharmacology and Biopharmaceutics Review(s) - AstraZeneca (Applicant)."