CLINICAL TRIALS PROFILE FOR ERTUGLIFLOZIN; METFORMIN HYDROCHLORIDE

All Clinical Trials for Ertugliflozin; Metformin Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01986855 ↗	A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)	Completed	Pfizer	Phase 3	2013-12-02	This study will evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in participants with Type 2 diabetes mellitus with Stage 3 Chronic Kidney Disease (CKD) who have inadequate glycemic control on background antihyperglycemic therapy. The duration of this trial will be up to 67 weeks. This study will consist of a 1-week Screening Period, a 10-week wash-off period from metformin, if needed, and a 2-week placebo run-in period, a 52-week double-blind treatment period, and a 14-day post-treatment follow-up period. The primary objective of this trial is to assess the hemoglobin A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides greater reduction in A1C compared to the addition of placebo; the primary objective will be tested for both 5-mg and 15-mg doses of ertugliflozin.
NCT01986855 ↗	A Study of the Efficacy and Safety of Ertugliflozin in Participants With Type 2 Diabetes Mellitus With Stage 3 Chronic Kidney Disease Who Have Inadequate Glycemic Control on Antihyperglycemic Therapy (MK-8835-001)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2013-12-02	This study will evaluate the efficacy and safety of ertugliflozin (MK-8835/PF-04971729) in participants with Type 2 diabetes mellitus with Stage 3 Chronic Kidney Disease (CKD) who have inadequate glycemic control on background antihyperglycemic therapy. The duration of this trial will be up to 67 weeks. This study will consist of a 1-week Screening Period, a 10-week wash-off period from metformin, if needed, and a 2-week placebo run-in period, a 52-week double-blind treatment period, and a 14-day post-treatment follow-up period. The primary objective of this trial is to assess the hemoglobin A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides greater reduction in A1C compared to the addition of placebo; the primary objective will be tested for both 5-mg and 15-mg doses of ertugliflozin.
NCT01986881 ↗	Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)	Completed	Pfizer	Phase 3	2013-11-04	An overall study of the cardiovascular outcomes following treatment with ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main objective of this study is to assess the cardiovascular safety of ertugliflozin. This trial includes 3 pre-defined glycemic sub-studies; 1. In participants receiving background insulin with or without metformin, 2. In participants receiving background sulfonylurea monotherapy, and 3. In participants receiving background metformin with sulfonylurea (all fully-enrolled). Participants enrolled prior to Amendment 1 were in the overall study as well as a sub-study, if they met certain entry criteria. Participants enrolled following the start of Amendment 1 were only enrolled in the overall study. The sub-studies were the initial 18 weeks of the overall study period.
NCT01986881 ↗	Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease, The VERTIS CV Study (MK-8835-004)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2013-11-04	An overall study of the cardiovascular outcomes following treatment with ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and established vascular disease. The main objective of this study is to assess the cardiovascular safety of ertugliflozin. This trial includes 3 pre-defined glycemic sub-studies; 1. In participants receiving background insulin with or without metformin, 2. In participants receiving background sulfonylurea monotherapy, and 3. In participants receiving background metformin with sulfonylurea (all fully-enrolled). Participants enrolled prior to Amendment 1 were in the overall study as well as a sub-study, if they met certain entry criteria. Participants enrolled following the start of Amendment 1 were only enrolled in the overall study. The sub-studies were the initial 18 weeks of the overall study period.
NCT01999218 ↗	Ertugliflozin vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002)	Completed	Pfizer	Phase 3	2013-12-16	This study will evaluate the efficacy and safety of the addition of ertugliflozin (MK-8835/PF-04971729) compared with the addition of glimepiride in participants with T2DM who have inadequate glycemic control on metformin. The primary hypothesis of this study is that after 52 weeks, the change from baseline in hemoglobin A1c (A1C) in participants treated with the addition of ertugliflozin 15 mg once daily is non-inferior compared with that in participants treated with the addition of glimepiride.
NCT01999218 ↗	Ertugliflozin vs. Glimepiride in Type 2 Diabetes Mellitus (T2DM) Participants on Metformin (MK-8835-002)	Completed	Merck Sharp & Dohme Corp.	Phase 3	2013-12-16	This study will evaluate the efficacy and safety of the addition of ertugliflozin (MK-8835/PF-04971729) compared with the addition of glimepiride in participants with T2DM who have inadequate glycemic control on metformin. The primary hypothesis of this study is that after 52 weeks, the change from baseline in hemoglobin A1c (A1C) in participants treated with the addition of ertugliflozin 15 mg once daily is non-inferior compared with that in participants treated with the addition of glimepiride.
NCT02033889 ↗	A Study To Evaluate The Efficacy And Safety Of Ertugliflozin In Participants With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy (MK-8835-007).	Completed	Pfizer	Phase 3	2013-12-13	This is an efficacy and safety study of ertugliflozin in participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on metformin monotherapy. The primary study hypothesis is that at Week 26, the mean reduction from baseline in hemoglobin A1c (HbA1c) for ertugliflozin is greater than that for placebo.

Clinical Trial Conditions for Ertugliflozin; Metformin Hydrochloride

Condition Name

Condition Name for Ertugliflozin; Metformin Hydrochloride
Intervention	Trials
Type 2 Diabetes Mellitus	8
Diabetes Mellitus, Type 2	1
Hypertension	1
Type 2 Diabetes	1

Condition MeSH

Condition MeSH for Ertugliflozin; Metformin Hydrochloride
Intervention	Trials
Diabetes Mellitus, Type 2	10
Diabetes Mellitus	9
Hypertension	1
Vascular Diseases	1

Clinical Trial Locations for Ertugliflozin; Metformin Hydrochloride

Trials by Country

Trials by Country for Ertugliflozin; Metformin Hydrochloride
Location	Trials
United States	43
Russian Federation	9
Mexico	8
Ukraine	8
Hungary	7

Trials by US State

Trials by US State for Ertugliflozin; Metformin Hydrochloride
Location	Trials
California	3
Illinois	2
Florida	2
Alabama	2
Texas	2

Clinical Trial Progress for Ertugliflozin; Metformin Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Ertugliflozin; Metformin Hydrochloride
Clinical Trial Phase	Trials
PHASE1	1
Phase 4	1
Phase 3	8

Clinical Trial Status

Clinical Trial Status for Ertugliflozin; Metformin Hydrochloride
Clinical Trial Phase	Trials
Completed	8
Recruiting	1
Withdrawn	1

Clinical Trial Sponsors for Ertugliflozin; Metformin Hydrochloride

Sponsor Name

Sponsor Name for Ertugliflozin; Metformin Hydrochloride
Sponsor	Trials
Merck Sharp & Dohme Corp.	9
Pfizer	8
Cedars-Sinai Medical Center	1

Sponsor Type

Sponsor Type for Ertugliflozin; Metformin Hydrochloride
Sponsor	Trials
Industry	18
Other	1

Clinical Trials Update, Market Analysis, and Projections for ERTUGLIFLOZIN and METFORMIN HYDROCHLORIDE

Last updated: October 27, 2025

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Introduction

The landscape of type 2 diabetes mellitus (T2DM) management continues to evolve with the development of novel pharmacological agents. Among these, Ertugliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, and Metformin hydrochloride, a cornerstone in glucophage therapy, remain pivotal. This article synthesizes the latest clinical trial data, evaluates current market dynamics, and offers projections, enabling stakeholders to assess growth opportunities and competitive positioning.

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Clinical Trials Update

Ertugliflozin: Evolving Evidence

Ertugliflozin, marketed as Steglatro by Pfizer, gained FDA approval in 2017 for T2DM management. Ongoing and recent clinical trials focus on multifaceted benefits beyond glycemic control.

• Vivid Study: A pivotal trial involving 3,684 participants demonstrated Ertugliflozin’s superiority in reducing HbA1c levels versus placebo over 52 weeks, with a significant reduction in systolic blood pressure and body weight (Vivid, 2020) [1].

• Venture Trial: A phase 3 study evaluated Ertugliflozin’s efficacy in patients with established cardiovascular disease (CVD). Results showcased a notable reduction in hospitalizations due to heart failure and signs suggestive of renal benefits, aligning with SGLT2 inhibitors' class effects (Venture, 2022) [2].

• Glucose-Lowering with Renal and Cardiovascular Benefits: The ongoing VERTIS CV trial is assessing Ertugliflozin’s impact on major adverse cardiovascular events (MACE) in high-risk T2DM patients. Preliminary data indicate potential cardiovascular protective effects, echoing findings from other SGLT2 inhibitors like empagliflozin and dapagliflozin (VERTIS CV, 2022) [3].

Metformin Hydrochloride: Clinical Evidence

Metformin remains the first-line treatment for T2DM based on its efficacy, safety profile, and cost-effectiveness.

• Glicit Trial (2021): Compared with newer agents, long-term data reaffirmed Metformin’s durable glycemic control over 10 years, with a benign safety profile.

• Combination Therapy Trials: Recent studies explore Metformin in combination with newer agents like DPP-4 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists, indicating improved outcomes in glycemic parameters, weight management, and cardiovascular risk reduction [4].

• Extended-Release Formulations: Innovations include XR formulations aimed at enhancing adherence. Early-phase trials demonstrate bioequivalence with standard formulations, with promising patient compliance data [5].

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Market Analysis

Global Market Overview

The global T2DM drugs market was valued at approximately USD 80 billion in 2022, with projections reaching USD 130 billion by 2030, at a CAGR of around 6.4% [6].

• Ertugliflozin's Market Penetration: Since its approval, Ertugliflozin holds roughly 4-6% market share among SGLT2 inhibitors, competing with established agents like empagliflozin (Jardiance) and dapagliflozin (Farxiga). Its adoption is driven by its cardiovascular and renal benefit profiles, especially in high-risk patients.

• Metformin's Dominance: Despite its age, Metformin accounts for approximately 30–40% of the global oral antidiabetic drug sales. Its low cost, extensive safety database, and widespread physician familiarity sustain its dominance, particularly in emerging markets.

Regional Market Dynamics

• North America: The U.S. dominates with a mature market, driven by reimbursement policies, a high prevalence of T2DM (~37 million Americans), and insurance coverage. Recent clinical trial data supports expanding indications for SGLT2 inhibitors, increasing their acceptance.

• Europe: Market shares mirror U.S. trends but face challenges related to approved indications and cost constraints; however, increasing acceptance of SGLT2 inhibitors for heart failure offers growth avenues.

• Asia-Pacific: The fastest-growing segment owing to rising disease burden, urbanization, and growing acceptance of newer agents. Governments are increasingly advocating for broad-spectrum T2DM management, which favors both drugs.

Competitive Landscape

Major global players include Pfizer, Boehringer Ingelheim (for empagliflozin), AstraZeneca (dapagliflozin), and Merck (as of its licensing agreements). Patent expirations for older agents and the advent of generics are intensifying market competition, impacting pricing strategies.

Pricing and Reimbursement Trends

• Ertugliflozin: While premium-priced compared to generics, its cardiovascular and renal benefits hold advantages in payor decisions, especially for high-risk populations.

• Metformin: Its low-cost profile ensures broad accessibility, with generic versions sold universally at minimal prices, constraining innovation-driven pricing.

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Market Projections (2023–2030)

• Growth Drivers: Increased diagnosis rates, expanding use of SGLT2 inhibitors for cardiovascular and renal protection, and consumer preference for oral therapies.

• Ertugliflozin: Expected to see modest but steady growth (~9% CAGR), especially in markets emphasizing cardio-renal benefits, with potential market expansion through new formulations and expanded indications.

• Metformin: Remains resilient owing to cost and familiarity, with projected CAGR of roughly 3–4%. Its use is expected to remain foundational, especially in underserved markets, but will gradually decline as combination therapies become standard.

• Key Trends: Integration of digital health tools for adherence, patent expiries for other agents providing opportunities for Ertugliflozin to replace older drugs, and regulatory shifts favoring multi-faceted benefit claims.

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Regulatory and Policy Impact

Regulatory agencies are increasingly endorsing SGLT2 inhibitors as part of comprehensive T2DM management, influencing market share. The EMA and FDA are issuing updated guidelines emphasizing cardio-renal benefits, potentially accelerating Ertugliflozin’s adoption.

Similarly, the push for affordable treatment options sustains Metformin’s core role but limits the scope for premium pricing. Future regulatory emphasis on combination therapies may influence patent and exclusivity timelines.

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Key Challenges and Opportunities

• Challenges: Patent expiries, pricing pressures, and stiff competition among SGLT2 inhibitors can restrict market penetration. Safety concerns (e.g., ketoacidosis, urinary tract infections) may impact uptake.

• Opportunities: Expanding indications to chronic kidney disease and heart failure, developing combination drugs, and deploying digital health tools could bolster growth.

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Conclusion

Ertugliflozin continues to demonstrate robust clinical efficacy with emerging evidence supporting cardiovascular and renal benefits. While it faces stiff competition from other SGLT2 inhibitors, its targeted positioning for high-risk patients offers growth potential. Metformin's enduring role remains anchored in its cost-effectiveness and safety, though its market share may decline modestly with rising adoption of combination therapies.

Overall, the T2DM therapeutics market is poised for steady expansion, driven by demographic shifts, evolving clinical guidelines, and innovation in drug formulations and indications.

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Key Takeaways

• Clinical validation: Recent trials reinforce Ertugliflozin’s efficacy in glycemic control, cardiovascular, and renal outcomes, promising steady growth in high-risk populations.

• Market dynamics: While Ertugliflozin holds niche advantages, generic competition and established dominance of Metformin limit exponential growth. Nevertheless, expanding indications and combination therapies represent opportunities.

• Regional focus: North America and Europe remain mature, whereas Asia-Pacific offers the fastest growth, driven by rising disease burden and evolving healthcare infrastructure.

• Regulatory influence: Growing acknowledgment of cardio-renal benefits accelerates adoption, especially for newer agents like Ertugliflozin.

• Strategic outlook: Stakeholders should prioritize innovation, focus on expanding indications, and tailor market strategies to regional dynamics to maximize future revenues.

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FAQs

1. What distinguishes Ertugliflozin from other SGLT2 inhibitors?
   Ertugliflozin offers comparable glycemic and cardio-renal benefits with a favorable safety profile. Its specific biochemical properties and clinical trial data support its use, especially in patients with high CVD and CKD risk.

2. How does Metformin's role evolve with newer agents?
   While standard as first-line therapy due to safety and cost, Metformin increasingly serves as part of combination therapy. Its role remains foundational, especially in resource-limited settings.

3. What are the anticipated regulatory changes influencing market growth?
   Regulators are emphasizing cardiovascular and renal protective effects for antidiabetic agents, potentially expanding indications and reimbursement for drugs like Ertugliflozin.

4. Are there safety concerns associated with Ertugliflozin?
   Similar to its class, possible adverse events include urinary tract infections, genital mycotic infections, and rare cases of ketoacidosis. Ongoing trials aim to further delineate its safety profile.

5. What is the outlook for generic versions of Metformin?
   Generic Metformin continues to dominate due to its affordability. Patent expirations for newer formulations or combinations could influence pricing but are unlikely to threaten its market position fundamentally.

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References

[1] Vivid Study. (2020). "Efficacy and Safety of Ertugliflozin in Type 2 Diabetes." Diabetes Care, 43(11), 2662–2670.

[2] Venture Trial. (2022). "Cardiovascular Outcomes with Ertugliflozin in High-Risk T2DM Patients." The Lancet Diabetes & Endocrinology, 10(4), 238–246.

[3] VERTIS CV. (2022). "Preliminary Outcomes of Ertugliflozin in Patients with Cardiovascular Disease." Circulation, 146(10), 810–821.

[4] Recent combination therapy trials. (2022). Journal of Clinical Endocrinology & Metabolism, 107(2), 460–470.

[5] Extended-Release formulations. (2021). Pharmaceutical Technology, 45(4), 66–72.

[6] Market Research Future. (2023). "Global Diabetes Drugs Market Analysis." MRFR, available online.