Glycaemic & Cardiovascular Treatment Outcomes of Voglibose Vs Glibenclamide Added to Metformin in T2DM Patients

NCT05688332 | Unknown Phase 3 DMC

• 4 other identifiers: 202112030076IRB Number: 00011000IORG Number: 0009227FWA Number: 00026270
• Study Type: interventional
• Target: 118
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to compare blood-sugar control and blood circulatory system risk-position in type 2 diabetes patients on voglibose versus those on glybenclamide when the two drugs are added to metformin because metformin alone is not controlling the blood-sugar well. The results of this trial will help in improving the health and treatment results of the type 2 diabetic patients. The main question the trial aims to answer is whether there is a difference in blood-sugar and blood circulatory system treatment results between voglibose + metformin and glibenclamide + metformin treatment combinations. Participants that agree to participate in the trial will be asked to provide a sample of blood so that the following measurable laboratory factors will be used to compare any differences in treatment results between the two treatment groups from the beginning to the end of the trial:

• Total Cholesterol (TC),
• Low Density Lipoproteins (LDL-c),
• High Density Lipoproteins (HDL-c),
• Fasting Triglycerides (FTG),
• Fasting blood sugar (FBS),
• Post prandial blood sugar (PPBG),
• Glycated hemoglobin (HbA1c) correlated to hemoglobin level,
• creatinine,
• blood urea and
• electrolytes (K+, Na+, Cl-).

Conditions

Diabetes Mellitus Type 2 Without Complication

Keywords

voglibose; Metformin; Glibenclamide; Outcomes

Outcome Measures

Primary Outcomes (2)

• Change in mean Glycated Hemoglobin (HbA1c) levels

  The null hypothesis is that there is no significant difference between the voglibose and glibenclamide treatment groups in the change in mean HbA1c levels after 6 weeks of add-on therapy to metformin in the T2DM patients (i.e. H0: µ1 = µ2 where µ1 is the mean HbA1c change in the glibenclamide group and µ2 is the mean HbA1c change in the voglibose group). The alternative hypothesis is that there is a significant difference between the voglibose and glibenclamide groups in the change in mean HbA1c levels after 6 weeks of add-on therapy to metformin in the T2DM patients (i.e. H1: µ1 ≠ µ2).

  Baseline & Week 6

• Change in mean Glycated Hemoglobin (HbA1c) levels

  The null hypothesis is that there is no significant difference between the voglibose and glibenclamide treatment groups in the change in mean HbA1c levels after 12 weeks of add-on therapy to metformin in the T2DM patients (i.e. H0: µ1 = µ2 where µ1 is the mean HbA1c change in the glibenclamide group and µ2 is the mean HbA1c change in the voglibose group). The alternative hypothesis is that there is a significant difference between the voglibose and glibenclamide groups in the change in mean HbA1c levels after 12 weeks of add-on therapy to metformin in the T2DM patients (i.e. H1: µ1 ≠ µ2).

  Baseline & Week 12

Secondary Outcomes (12)

• Change in Glycemic control with regard to Fasting Plasma Glucose (FPG)

  Baseline & week 6

• Change in glycemic control with regard to Fasting Plasma Glucose (FPG)

  Baseline & week 12

• Change in glycemic control with regard to Post Prandial Blood Glucose (PPBG)

  Baseline & week 6

• Change in glycemic control with regard to Post Prandial Blood Glucose (PPBG)

  Baseline & week 12

• Lipid profile (LDL-c, HDL-c, TC, TG) comparison

  Baseline & Week 6

Study Arms (2)

Voglibose + Metformin (Group B)

EXPERIMENTAL

In the B treatment group, 59 participants will be randomly assigned to initially voglibose 0.2mg TDS immediately before meals + metformin 500mg BD immediately before meals daily. Individual drug doses will be adjusted to the next higher doses after 6 to 12 days, at next clinical visits based on home based recorded blood glucose profiles. The maximum daily recommended dose of metformin of 2g and voglibose 0.9mg will not be exceeded.

Drug: Voglibose + Metformin

Glibenclamide + Metformin (Group A)

ACTIVE COMPARATOR

In treatment group A, 59 participants will initially be randomly allocated by study team members to the glibenclamide 5mg O.D + metformin 500mg BD regimen. In this study, 10mg glibenclamide and 2g metformin will not be exceeded daily.

Drug: Glibenclamide + Metformin

Interventions

Voglibose + Metformin DRUG

In treatment group B, 59 participants will also be randomly assigned to the voglibose 0.2/0.3mg TDS + metformin 500mg BD treatment combination to be taken orally daily, during or immediately after meals with dose titration at day 6 and 12 if the average fasting blood glucose (FBG) level is ≥7 mmol/L (126 mg/dL) and then dosage will be maintained for the remainder of the treatment period Participants in the intervention group initially receiving voglibose 0.2mg + metformin 500mg BD will be dose-titrated to voglibose 0.3mg +metformin 1g BD. The duration of therapy for each participant will be 12 weeks, which is the minimum period for evaluating the primary endpoint.

Voglibose + Metformin (Group B)

Glibenclamide + Metformin DRUG

The drugs (glibenclamide + metformin), in the control or comparator group will also be taken orally, glibenclamide once a day (OD) before meals, and metformin twice a day (BD) also before meals. These drugs will also be taken with a dose-titration at days 6 and 12 if the average is FBG level will be ≥ 7 mmol/L and the dose will be maintained for the remainder of the study period. The duration of therapy for each participant will be 12 weeks, which is the minimum period for evaluating the primary endpoint. In this group, participants will initially receive glibenclamide 5mg once daily (OD) + metformin 500mg BD then will be dose-titrated to glibenclamide 10mg OD + metformin 1g BD.

Glibenclamide + Metformin (Group A)

Eligibility Criteria

• Age: 22 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study1 procedures and availability for the durtion of the study.
• Male or female, aged 22-59 years.
• In good general health as evidenced by medical history, diagnosed with T2DM and on tolerated dose of at least 2g/day of metformin monotherapy.
• Ability to take oral medication and be willing to adhere to the medication regimen through out the study period.
• For females of reproductive potential use of highly effective contraception.
• Native-Zambian participants
• Must be on metformin monotherapy for 12 weeks or longer.
• Glycated haemoglobin (HbA1c) must be \>7.0% within 12 weeks before screening.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Hypersensitivity or contraindication to AGIs
• Hypersensitivity or contraindication to SUs
• Type 2 diabetes patients with pregnancy or lactation
• Patients with acute complications like diabetic ketoacidosis, or hyperosmolar hyperglycaemic state at the time of screening
• Patients with established cardiovascular disease, e.g.; HF, coronary artery disease
• Patients with altered haemoglobin levels, e.g.; in conditions like anaemias and haemoglobimopathies such as thalassemia
• Patients on concomitant corticosteroid therapy.

Sponsors & Collaborators

• University of Zambia: lead
• University Teaching Hospital, Lusaka, Zambia: collaborator

Related Publications (4)

• American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Suppl 1):S17-S38. doi: 10.2337/dc22-S002.

  PMID: 34964875 BACKGROUND

• Rosenquist KJ, Fox CS. Mortality Trends in Type 2 Diabetes. In: Cowie CC, Casagrande SS, Menke A, Cissell MA, Eberhardt MS, Meigs JB, Gregg EW, Knowler WC, Barrett-Connor E, Becker DJ, Brancati FL, Boyko EJ, Herman WH, Howard BV, Narayan KMV, Rewers M, Fradkin JE, editors. Diabetes in America. 3rd edition. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases (US); 2018 Aug. CHAPTER 36. Available from http://www.ncbi.nlm.nih.gov/books/NBK568010/

  PMID: 33651566 BACKGROUND

• Coleman RL, Scott CAB, Lang Z, Bethel MA, Tuomilehto J, Holman RR. Meta-analysis of the impact of alpha-glucosidase inhibitors on incident diabetes and cardiovascular outcomes. Cardiovasc Diabetol. 2019 Oct 17;18(1):135. doi: 10.1186/s12933-019-0933-y.

  PMID: 31623625 BACKGROUND

• Akmal M, Patel P, Wadhwa R. Alpha Glucosidase Inhibitors. 2024 Feb 28. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK557848/

  PMID: 32496728 BACKGROUND

MeSH Terms

Interventions

voglibose; Metformin; Glyburide

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Sulfonylurea Compounds; Urea; Amides; Sulfones; Sulfur Compounds

Central Study Contacts

Brown Kamanga, MMed

CONTACT

+260 97 2758137; brownkamanga@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 27, 2022
• First Posted: January 18, 2023
• Study Start: August 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: January 1, 2024
• Last Updated: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact lawrencemukela@gmail.com