Oral Combination of Glimepiride/Vildagliptin/Metformin in Patients With T2D and Dual Treatment Failure

NCT04841096 | Completed Phase 3

• 1 other identifier: SIL-30013-III-20(1)
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 5

Brief Summary

Phase IIIb, randomized, multicenter, double-blind, prospective study to evaluate the efficacy and safety of a daily fixed-dose combination of glimepiride / vildagliptin / metformin in patients with type 2 diabetes with a history of dual treatment failure and combined or individual oral antidiabetics with SGLT2 / Metformin, Biguanide / Sulfonylurea, Sulfonylurea / iDPP4 or Biguanide / iDPP4. To evaluate the changes in the percentage of HbA1c at 3 and 6 months with regard to their baseline measurement.

Conditions

Type 2 Diabetes

Keywords

Type 2 diabetes; Combine therapy; Hypoglycemic agents

Outcome Measures

Primary Outcomes (3)

• Compare changes in HbA1

  Mean change in HbA1c

  baseline, 3 and 6 months of treatment

• Proportion of patients who change their HbA1c concentration

  Proportion of patients who change their HbA1c by at least 1 percent

  baseline, 3 and 6 months of treatment

• Mean difference change between groups in HbA1c concentration

  Difference greater than 0.3 between group A and B HbA1c concentration

  baseline, 3 and 6 months of treatment

Secondary Outcomes (2)

• Mean glucose change

  baseline, 3 and 6 months of treatment

• Incidence of adverse events and reactions

  baseline, 3 and 6 months of treatment

Study Arms (4)

Group A1: Glimepiride (1mg) / Vildagliptin (50mg) / Metformin (500mg).

EXPERIMENTAL

Tablets, orally, once a day. Initial dose for the first 45 days of intervention.

Drug: A1=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg)

Group B1: Glimepiride (1mg) / Vildagliptin (50mg) / Metformin (500mg)

EXPERIMENTAL

Tablets, orally, once a day. Initial dose for the first 45 days of intervention.

Drug: B2=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg)

Group A2: Glimepiride (2mg) / Vildagliptin (50mg) / Metformin (1000mg)

EXPERIMENTAL

Tablets, orally, once a day. Dose escalation if the patients meets established criteria.

Drug: (A2) Glimepiride/Vildagliptin/Metformin

Group B2: Glimepiride (4mg) / Vildagliptin (50mg) / Metformin (1000mg)

EXPERIMENTAL

Tablets, orally, once a day. Dose escalation if the patients meets established criteria.

Drug: (B2) Glimepiride/Vildagliptin/Metformin

Interventions

A1=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg) DRUG

Take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Initial dose for the first 45 days of intervention.

Also known as: (A1) Glimepiride/Vildagliptin/Metformin

Group A1: Glimepiride (1mg) / Vildagliptin (50mg) / Metformin (500mg).

B2=Glimepiride / Vildagliptin / Metformin (1 mg/ 50 mg/ 500 mg) DRUG

take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Initial dose for the first 45 days of intervention.

Also known as: (B1) Glimepiride/Vildagliptin/Metformin

Group B1: Glimepiride (1mg) / Vildagliptin (50mg) / Metformin (500mg)

(A2) Glimepiride/Vildagliptin/Metformin DRUG

Take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Escalation dose in cause the patient meets established criteria.

Also known as: A2=Glimepiride / Vildagliptin / Metformin (2 mg/ 50 mg/ 1000 mg)

Group A2: Glimepiride (2mg) / Vildagliptin (50mg) / Metformin (1000mg)

(B2) Glimepiride/Vildagliptin/Metformin DRUG

Take one tablet of the prescribed dose of the investigational drug by mouth, preferably with food and in the morning. Escalation dose in cause the patient meets established criteria.

Also known as: B2=Glimepiride / Vildagliptin / Metformin (4 mg/ 50 mg/ 1000 mg)

Group B2: Glimepiride (4mg) / Vildagliptin (50mg) / Metformin (1000mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female.
• Age \>18 years old at the beginning of the study.
• Diagnosis of type 2 diabetes prior to the start of the study.
• Therapeutic failure to a dual treatment with SGLT2 / Metformin, Biguanide / Sulfonylurea, Sulfonylurea / iDPP4, Biguanide / iDPP4.
• HbA1c ≥ 7.5% and ≤ 11% during screening tests.
• Women of childbearing potential using a contraceptive method (barrier, oral hormonal, injectable, subdermal) or naturally or surgically sterile in menopause.
• Subject agree to participate in the study and give informed consent in writing.

You may not qualify if:

• The drug is contraindicated for medical reasons.
• History of Type 1 Diabetes Mellitus.
• History of metabolic complications such as ketoacidosis or nonketotic hyperosmolar state.
• History of gastric bariatric surgery or gastric band in the last year.
• History of drug or alcohol abuse in the past year.
• Body Mass Index \<20 kg/m2 and \>40 kg/m2.
• Acute or severe renal dysfunction (glomerular filtration \<30 ml / min / 1.72 m2).
• History of chronic liver disease or ALT and / or AST ≥3 times the normal upper limit and / or Total Bilirubin\> 2.5 times the upper limit of normal, or GGT ≥3 times the upper limit of normal.
• Pregnant and / or lactating women.
• The patient is participating in another clinical study involving an investigational treatment or participated in one in the previous 4 weeks.
• At medical criteria, a disease that affects the prognosis and prevents outpatient management, for example, but not restricted to: end-stage cancer, kidney, heart, respiratory or liver failure, mental illness, with scheduled surgical or hospital procedures.
• Be a patient with a working relationship with the main researcher or the research center or deprived of liberty.

Sponsors & Collaborators

• Laboratorios Silanes S.A. de C.V.: lead

Study Sites (5)

Centro de Investigación y Avances Médicos Especializados

Cancún, Quintana Roo, 77506, Mexico

Location

Mérida Investigación Clínica

Mérida, Yucatán, 97125, Mexico

Location

Centro de Investigación Médica Aguascalientes

Aguascalientes, 20116, Mexico

Location

Oaxaca Site Management Organization SC.

Oaxaca City, 68000, Mexico

Location

Oncológico Potosino

San Luis Potosí City, 78250, Mexico

Location

Related Publications (14)

• American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020 Jan;43(Suppl 1):S14-S31. doi: 10.2337/dc20-S002.

  PMID: 31862745 BACKGROUND

• Cahn A, Raz I, Kleinman Y, Balicer R, Hoshen M, Lieberman N, Brenig N, Del Prato S, Cefalu WT. Clinical Assessment of Individualized Glycemic Goals in Patients With Type 2 Diabetes: Formulation of an Algorithm Based on a Survey Among Leading Worldwide Diabetologists. Diabetes Care. 2015 Dec;38(12):2293-300. doi: 10.2337/dc15-0187. Epub 2015 Oct 30.

  PMID: 26519337 BACKGROUND

• Cramer JA. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004 May;27(5):1218-24. doi: 10.2337/diacare.27.5.1218.

  PMID: 15111553 BACKGROUND

• Rubin RR. Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus. Am J Med. 2005 May;118 Suppl 5A:27S-34S. doi: 10.1016/j.amjmed.2005.04.012.

  PMID: 15850551 BACKGROUND

• Khunti K, Kosiborod M, Ray KK. Legacy benefits of blood glucose, blood pressure and lipid control in individuals with diabetes and cardiovascular disease: Time to overcome multifactorial therapeutic inertia? Diabetes Obes Metab. 2018 Jun;20(6):1337-1341. doi: 10.1111/dom.13243. Epub 2018 Mar 11.

  PMID: 29405543 BACKGROUND

• Orozco-Beltran D, Mata-Cases M, Artola S, Conthe P, Mediavilla J, Miranda C. [Adherence of Type 2 Diabetes Mellitus approach: Current situation and possible solutions]. Aten Primaria. 2016 Jun-Jul;48(6):406-20. doi: 10.1016/j.aprim.2015.09.001. Epub 2016 Jan 13. Spanish.

  PMID: 26775266 BACKGROUND

• Garber AJ, Handelsman Y, Grunberger G, Einhorn D, Abrahamson MJ, Barzilay JI, Blonde L, Bush MA, DeFronzo RA, Garber JR, Garvey WT, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Perreault L, Rosenblit PD, Samson S, Umpierrez GE. CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2020 EXECUTIVE SUMMARY. Endocr Pract. 2020 Jan;26(1):107-139. doi: 10.4158/CS-2019-0472. No abstract available.

  PMID: 32022600 BACKGROUND

• Lukashevich V, Del Prato S, Araga M, Kothny W. Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea. Diabetes Obes Metab. 2014 May;16(5):403-9. doi: 10.1111/dom.12229. Epub 2013 Dec 2.

  PMID: 24199686 BACKGROUND

• Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal JB, Bolen S. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann Intern Med. 2016 Jun 7;164(11):740-51. doi: 10.7326/M15-2650. Epub 2016 Apr 19.

  PMID: 27088241 BACKGROUND

• Dennis JM, Henley WE, Weedon MN, Lonergan M, Rodgers LR, Jones AG, Hamilton WT, Sattar N, Janmohamed S, Holman RR, Pearson ER, Shields BM, Hattersley AT; MASTERMIND Consortium. Sex and BMI Alter the Benefits and Risks of Sulfonylureas and Thiazolidinediones in Type 2 Diabetes: A Framework for Evaluating Stratification Using Routine Clinical and Individual Trial Data. Diabetes Care. 2018 Sep;41(9):1844-1853. doi: 10.2337/dc18-0344. Epub 2018 Aug 2.

  PMID: 30072404 BACKGROUND

• Bianchi C, Daniele G, Dardano A, Miccoli R, Del Prato S. Early Combination Therapy with Oral Glucose-Lowering Agents in Type 2 Diabetes. Drugs. 2017 Mar;77(3):247-264. doi: 10.1007/s40265-017-0694-4.

  PMID: 28155046 BACKGROUND

• U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes. 1995 Nov;44(11):1249-58.

  PMID: 7589820 BACKGROUND

• Levy J, Atkinson AB, Bell PM, McCance DR, Hadden DR. Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study. Diabet Med. 1998 Apr;15(4):290-6. doi: 10.1002/(SICI)1096-9136(199804)15:43.0.CO;2-M.

  PMID: 9585393 BACKGROUND

• Benford M, Milligan G, Pike J, Anderson P, Piercy J, Fermer S. Fixed-dose combination antidiabetic therapy: real-world factors associated with prescribing choices and relationship with patient satisfaction and compliance. Adv Ther. 2012 Jan;29(1):26-40. doi: 10.1007/s12325-011-0096-z. Epub 2012 Jan 12.

  PMID: 22246944 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Vildagliptin; Metformin; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Study Officials

• Salvador Pérez Jaime, M.D

  Centro de Investigación Médica Aguascalientes (Red OSMO)

  PRINCIPAL INVESTIGATOR

• Juan A Becerra Hernández, M.D

  Centro de Investigación y Avances Médicos Especializados (Red OSMO)

  PRINCIPAL INVESTIGATOR

• Ana L Flores Barranco, M.D

  Oaxaca Site Management Organization SC. (Red OSMOS)

  PRINCIPAL INVESTIGATOR

• Abraham S Álvarez, M.D

  Oncológico Potosino (Red OSMO)

  PRINCIPAL INVESTIGATOR

• Victor C Bohórquez López, M.D

  Mérida Investigación Clínica (Red OSMO)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 12, 2021
• Study Start: March 21, 2023
• Primary Completion: March 15, 2024
• Study Completion: May 15, 2024
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

ME (5)