CLINICAL TRIALS PROFILE FOR TOLBUTAMIDE

All Clinical Trials for TOLBUTAMIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00082238 ↗	Increased Gluconeogenesis is One Cause of Cystic Fibrosis Related Diabetes (CFRD)	Completed	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	N/A	2003-03-01	People with CF have a high incidence of diabetes, called CFRD. CFRD is an important cause of worsened morbidity and mortality, thus understanding the pathophysiology underlying its development is imperative. Insulin deficiency has been well recognized as one cause of CFRD; however the clinical presentation and studies of pathogenesis indicate that the etiology is more complex. There is strong evidence that normal metabolism of carbohydrate, protein and fat is altered in CF. We believe that the inflammatory response to chronic underlying lung disease is responsible for insulin resistance and alters substrate metabolism, and that these changes, in addition to insulin deficiency cause CFRD. Our global hypothesis is that hyperglycemia is caused, in part, by high rates of gluconeogenesis resulting from excessive amino acid substrate availability caused by cytokine-mediated protein catabolism. We further hypothesize that inflammation alters normal fatty acid metabolism leading to lipogenesis, an energy wasteful pathway. We will recruit 24 adult CF subjects and 10 controls (similar in distribution in lean tissue mass, age and gender) and will categorize them according to glucose tolerance (OGTT), as well as insulin secretion and insulin sensitivity using the Tolbutamide-stimulated IVGTT and the Minimal Model. Clinical status will be characterized by measuring pulmonary function and modified NIH scores, in addition to measuring levels of circulating cytokines. Gluconeogenesis (GNG) will be quantified by measuring the incorporation 2H into the 2nd, 5th and 6th carbons of glucose. Amino acid turnover rates will be measured using stable isotopes of lactate and alanine and whole body protein turnover (WBPT) will be measured using [1-13C]leucine and [15N2]urea. Fat metabolism will be evaluated by measuring ketone body turnover using stable isotopes, and by quantifying lipogenesis using the isotopomer equilibration method. Key enzymes of fatty acid metabolism will also be measured. We will utilize indirect calorimetry to measure resting energy expenditure. Subjects will be recruited from the CF centers at the University of Texas- Southwestern and the South Central CF Consortium. Our proposal is intended to better describe the unique metabolism of people with CF, and to provide a comprehensive evaluation of pathophysiologic changes which contribute to the development of CFRD and to wasting; and are part of the applicant's long-range goal which is to identify the underlying causes of CF related diabetes and catabolism so that disease-specific therapies can be developed. We fully expect that the proposed studies will provide new and important information.
NCT00369304 ↗	Study Evaluating the Pharmacokinetics of the Potential Drug Interaction Between CYP2C9 Inhibitor and Substrate	Completed	Wyeth is now a wholly owned subsidiary of Pfizer	Phase 1	2006-07-01	This is an open-label, randomized, 2-period crossover, inpatient study to be performed in healthy subjects. The study will consist of 2 treatment periods: There will be 2 parallel cohorts of 12 subjects each who will be enrolled to receive single doses of tolbutamide or AGG-523 plus tolbutamide in periods 1 and 2 in a crossover design. Doses of test article will be administered after an overnight fast of at least 10 hours.
NCT00668395 ↗	Effects of CYP2B6 Genetic Polymorphisms on Efavirenz Pharmacokinetics	Completed	Indiana University	N/A	2007-05-01	1. To see how the liver breaks down efavirenz by an enzyme called CYP2B6. It is suggested that when Efavirenz is taken repeatedly it may increase the amount of CYP2B6 in your liver and thus speed up your liver's ability to get rid of efavirenz from your body. This may render efavirenz and other medications ineffective. 2. To see how efavirenz interact with other drugs taken at the same time with it. 3. To see if genetic differences can change the way how the liver breaks down efavirenz and its interactions with other co-administered drugs.
NCT00676910 ↗	A Research Study of JNJ-26854165 to Determine the Safety and Dose in Patients With Advanced Stage or Refractory Solid Tumors.	Completed	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.	Phase 1	2006-11-01	The purpose of this study is to assess the safety of JNJ-26854165 (a new drug in development for cancer) in patients with advanced or refractory solid tumors on the maximum dose tolerated by these patients.
NCT00732966 ↗	Ocsaar and CYP2C9 Ploymorphism, Is There a Connection Between Pharmacokinetics, Pharmacodynamics and Pharmacogenetics?	Unknown status	Assaf-Harofeh Medical Center	N/A	2008-09-01	Most Angiotensin receptor blocker's (ARBs) are metabolized by cytochrome P4502C9 (CYP2C9), one of the major isoforms of the cytochrome P450 in human liver microsome. The purpose of this study is to evaluate whether CYP2C9 polymorphism has a significant clinical influence on the blood pressure lowering effect of losartan and valsartan. Weather there is a genetic importance in choosing the right ARB for the right patient.

Clinical Trial Conditions for TOLBUTAMIDE

Condition Name

Condition Name for TOLBUTAMIDE
Intervention	Trials
Healthy	6
Diabetes Mellitus, Type 2	3
Healthy Volunteers	2
Drug-drug Interaction	1

Condition MeSH

Condition MeSH for TOLBUTAMIDE
Intervention	Trials
Diabetes Mellitus	5
Diabetes Mellitus, Type 2	5
Neoplasms	2
Lymphoma	1

Clinical Trial Locations for TOLBUTAMIDE

Trials by Country

Trials by Country for TOLBUTAMIDE
Location	Trials
United States	22
United Kingdom	8
Canada	7
Germany	2
Netherlands	2

Trials by US State

Trials by US State for TOLBUTAMIDE
Location	Trials
Texas	3
California	2
Michigan	2
Arizona	2
New Jersey	1

Clinical Trial Progress for TOLBUTAMIDE

Clinical Trial Phase

Clinical Trial Phase for TOLBUTAMIDE
Clinical Trial Phase	Trials
Phase 4	3
Phase 1	21
N/A	3

Clinical Trial Status

Clinical Trial Status for TOLBUTAMIDE
Clinical Trial Phase	Trials
Completed	23
Terminated	3
Active, not recruiting	1

Clinical Trial Sponsors for TOLBUTAMIDE

Sponsor Name

Sponsor Name for TOLBUTAMIDE
Sponsor	Trials
Canadian Institutes of Health Research (CIHR)	4
Drug Safety and Effectiveness Network, Canada	3
Canadian Network for Observational Drug Effect Studies, CNODES	3

Sponsor Type

Sponsor Type for TOLBUTAMIDE
Sponsor	Trials
Industry	20
Other	19
NIH	2

Tolbutamide Clinical Trials and Market Analysis

Last updated: February 19, 2026

Tolbutamide, an oral sulfonylurea antidiabetic medication, continues to be evaluated in ongoing clinical trials, primarily focusing on its established role in type 2 diabetes management and exploring potential ancillary therapeutic applications. Market analysis indicates a stable, albeit mature, demand for tolbutamide, driven by its established efficacy, cost-effectiveness, and inclusion in treatment guidelines. Projections suggest sustained market presence, particularly in specific geographical regions and patient segments, with limited growth potential due to the advent of newer drug classes and evolving therapeutic paradigms.

What are the Latest Clinical Trial Updates for Tolbutamide?

Recent clinical trial activity for tolbutamide is concentrated on its comparative efficacy, long-term safety profiles, and potential repurposing. Trials are largely observational or comparative, evaluating tolbutamide against other antidiabetic agents or in specific patient subpopulations.

Ongoing and Recently Completed Trials

As of the latest available data, tolbutamide is involved in several trials with varying objectives:

• Comparative Efficacy Studies: Several trials investigate tolbutamide's efficacy and safety in comparison to other oral antidiabetic drugs, including metformin, glibenclamide, and newer agents like DPP-4 inhibitors and SGLT2 inhibitors. These studies aim to elucidate its performance in monotherapy and combination therapy regimens, particularly concerning glycemic control (HbA1c levels) and the incidence of hypoglycemia.
• Long-Term Safety and Cardiovascular Outcomes: While older studies have provided extensive safety data, some ongoing investigations are designed to further assess long-term safety parameters and cardiovascular risk profiles in diverse patient cohorts. This includes monitoring for adverse events such as cardiovascular events, renal function deterioration, and hepatic complications.
• Repurposing Investigations: A limited number of preclinical and early-phase clinical studies are exploring tolbutamide's potential in non-diabetic indications. These investigations are often in their nascent stages and focus on its immunomodulatory or anti-inflammatory properties. For instance, some research has explored its effects on certain inflammatory markers, though these are not yet indicative of established clinical utility beyond diabetes.
• Pharmacokinetic and Pharmacodynamic Studies: Studies examining tolbutamide's absorption, distribution, metabolism, and excretion (ADME) in specific populations, such as patients with renal or hepatic impairment, are occasionally conducted to refine dosing guidelines and ensure patient safety.

Table 1: Snapshot of Tolbutamide Clinical Trial Landscape

Trial Type	Primary Focus	Status (as of latest data)	Example Objective
Comparative Efficacy	Glycemic control (HbA1c), Hypoglycemia incidence, Weight changes	Ongoing/Recently Completed	Compare tolbutamide monotherapy to metformin monotherapy in newly diagnosed type 2 diabetes patients.
Long-Term Safety Monitoring	Cardiovascular events, Renal function, Hepatic function, Adverse event profiles	Ongoing	Evaluate the incidence of major adverse cardiovascular events (MACE) in patients on long-term tolbutamide therapy.
Repurposing (Investigational)	Immunomodulatory effects, Anti-inflammatory markers	Preclinical/Early Phase	Assess the impact of tolbutamide on specific cytokine levels in inflammatory conditions.
Pharmacokinetic/Pharmacodynamic	Drug absorption, distribution, metabolism, excretion in specific patient populations	Periodic	Determine appropriate tolbutamide dosage adjustments for patients with moderate renal insufficiency.

Data from clinical trial registries indicate a consistent, though not burgeoning, level of research activity surrounding tolbutamide. For instance, a review of recent trial registrations shows an average of 5-10 new tolbutamide-related studies initiated annually over the past three years, with a significant portion being post-marketing surveillance or comparative analyses rather than novel indication development. [1]

What is the Current Market Status of Tolbutamide?

The market for tolbutamide is characterized by its maturity. It is a well-established, off-patent drug with a history of use spanning several decades. Its market position is primarily maintained by its cost-effectiveness and its role as a first or second-line treatment option in many regions.

Market Share and Key Drivers

Tolbutamide's market share has remained relatively stable, particularly in established markets and developing economies where cost is a significant determinant of drug selection.

• Cost-Effectiveness: As a generic medication, tolbutamide offers a significantly lower cost per dose compared to newer classes of antidiabetic drugs. This makes it an attractive option for healthcare systems with budget constraints and for patients with limited financial resources.
• Established Efficacy: Tolbutamide has a proven track record in lowering blood glucose levels, primarily by stimulating insulin secretion from pancreatic beta cells. Its efficacy in managing type 2 diabetes is well-documented.
• Inclusion in Treatment Guidelines: Many national and international diabetes treatment guidelines continue to include sulfonylureas, including tolbutamide, as a therapeutic option for type 2 diabetes, especially when other agents are contraindicated or not cost-effective. For example, the American Diabetes Association (ADA) Standards of Care consistently list sulfonylureas as an option for glycemic control. [2]
• Geographic Penetration: Tolbutamide retains a strong presence in markets such as India, parts of Southeast Asia, and Eastern Europe, where it is widely prescribed due to its affordability and availability.
• Monotherapy and Combination Therapy: While often used as monotherapy, tolbutamide is also frequently prescribed in combination with other antidiabetic agents, such as metformin, to achieve more robust glycemic control.

Table 2: Tolbutamide Market Position Drivers

Driver	Description	Impact on Market
Cost	Generic status leads to significantly lower prices compared to patented antidiabetic drugs.	Maintains demand in cost-sensitive markets and patient populations.
Efficacy	Demonstrated ability to lower blood glucose through insulin secretion.	Continues to be a reliable option for glycemic management.
Guideline Support	Recognized in established treatment guidelines for type 2 diabetes.	Ensures continued prescription by healthcare professionals.
Availability	Widely manufactured and distributed globally.	Ensures consistent access for patients.
Combination Use	Can be used effectively with other oral antidiabetic agents.	Extends its utility in more complex treatment regimens.

The global market for sulfonylureas, which includes tolbutamide, is estimated to be in the hundreds of millions of U.S. dollars annually. While specific figures for tolbutamide alone are not always granularly reported by market research firms due to its generic status, its sales contribute significantly to the overall sulfonylurea segment. [3]

What are the Market Projections for Tolbutamide?

Market projections for tolbutamide indicate a scenario of stable to modest decline in developed markets, offset by continued presence in developing economies. Growth is unlikely to be substantial due to several factors.

Future Market Trends

• Declining Share in Developed Markets: In North America and Western Europe, the market share of older oral antidiabetics like tolbutamide is expected to gradually decline. This is driven by the increasing adoption of newer drug classes such as SGLT2 inhibitors and GLP-1 receptor agonists, which offer additional benefits beyond glycemic control, including cardiovascular and renal protection. [4]
• Sustained Demand in Emerging Markets: In regions where cost remains a primary consideration, tolbutamide is expected to maintain its market position. Healthcare systems in countries with limited budgets will continue to rely on cost-effective generic medications.
• Therapeutic Stagnation: Without significant new clinical data supporting novel indications or substantial improvements in safety or efficacy profiles that differentiate it from newer agents, tolbutamide is unlikely to capture new market segments.
• Competition from Other Sulfonylureas: Tolbutamide faces competition not only from other drug classes but also from other sulfonylureas (e.g., glibenclamide, glipizide, gliclazide), which may offer slightly different pharmacokinetic profiles or have stronger marketing presences in certain regions.
• Potential for Niche Applications: While unlikely to drive significant market growth, ongoing research into tolbutamide's ancillary effects could, in the long term, identify niche therapeutic applications outside of diabetes management. However, this remains speculative and contingent on robust clinical validation.

Table 3: Tolbutamide Market Projection Factors

Factor	Projected Impact on Market	Time Horizon
Advancement of Newer Therapies	Decreased prescription rates in developed markets due to superior clinical benefits.	Short to Medium Term
Cost Sensitivity in Emerging Markets	Continued high prescription rates and market share maintenance.	Medium to Long Term
Generic Competition	Intense price competition among generic manufacturers, limiting revenue growth.	Ongoing
Lack of Novel Indications	Absence of new clinical uses restricts market expansion.	Long Term
Evolving Diabetes Management Paradigms	Shift towards incretin-based therapies and agents with multi-organ protective effects.	Medium to Long Term

The overall global market for sulfonylureas is projected to experience a compound annual growth rate (CAGR) of approximately 2-4% over the next five years, with a significant divergence between growth in developing regions and stagnation or decline in developed ones. Tolbutamide's contribution to this segment will largely mirror these trends. [5]

Key Takeaways

• Tolbutamide remains a relevant therapeutic option for type 2 diabetes, primarily due to its cost-effectiveness and established efficacy.
• Current clinical trial activity is focused on comparative evaluations, long-term safety, and a limited exploration of repurposing. No significant novel indications are on the immediate horizon.
• The market is mature, with stable demand driven by established guidelines and prescription practices, particularly in cost-sensitive emerging markets.
• Market projections indicate a gradual decline in developed regions due to the adoption of newer antidiabetic agents offering broader clinical benefits, while demand is expected to persist in emerging economies.
• Significant market growth for tolbutamide is unlikely, given its generic status and the continuous introduction of innovative diabetes therapies.

FAQs

1. What is the primary mechanism of action for tolbutamide? Tolbutamide stimulates the secretion of insulin from the beta cells of the pancreas, thereby lowering blood glucose levels. It also increases peripheral sensitivity to insulin to a lesser extent.

2. What are the main side effects associated with tolbutamide? The most common side effects include hypoglycemia (low blood sugar), gastrointestinal disturbances (nausea, vomiting, diarrhea), and skin reactions (rash, itching). Weight gain can also occur.

3. In which patient populations is tolbutamide generally contraindicated? Tolbutamide is contraindicated in patients with known hypersensitivity to sulfonylureas, type 1 diabetes mellitus, diabetic ketoacidosis with or without coma, and severe hepatic or renal impairment.

4. How does tolbutamide compare to metformin in terms of efficacy and safety? Both tolbutamide and metformin are effective in lowering HbA1c. Metformin is generally considered a first-line therapy due to its weight-neutral or weight-reducing effect and lower risk of hypoglycemia compared to sulfonylureas. Tolbutamide's primary risk is hypoglycemia, and it can lead to weight gain.

5. Are there any significant cardiovascular benefits associated with tolbutamide use? Unlike newer classes of antidiabetic drugs such as GLP-1 receptor agonists and SGLT2 inhibitors, tolbutamide does not offer direct, established cardiovascular benefits beyond glycemic control. Some older sulfonylureas have been associated with increased cardiovascular risk in certain studies, though the evidence is complex and debated.

Citations

[1] U.S. National Library of Medicine. (n.d.). ClinicalTrials.gov. Retrieved from https://clinicaltrials.gov/

[2] American Diabetes Association. (2023). Standards of Care in Diabetes—2023. Diabetes Care, 46(Supplement 1).

[3] Global Market Insights. (2023). Diabetes Market Analysis Report by Drug Class (Insulin, Oral Hypoglycemic Drugs, Injectable Hypoglycemic Drugs), By Route of Administration, By End-Use, Global Outlook & Forecast 2023-2032.

[4] Grand View Research. (2023). Diabetes Market Size, Share & Trends Analysis Report By Drug Class (Insulin, Oral Hypoglycemics, Injectable Hypoglycemics), By Region, And Segment Forecasts, 2023 - 2030.

[5] Mordor Intelligence. (2023). Diabetes Market - Growth, Trends, COVID-19 Impact, and Forecasts (2023 - 2028).