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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.
To achieve glycemic control goals, a combination of medications with complementary mechanisms of action, with fasting and postprandial effects, may be required to achieve and maintain clinically acceptable glycemic control in some patients. A fixed combination of two or more therapeutic agents with complementary mechanisms of action makes it possible to optimize compliance and adherence to treatment among patients with T2D because it is administered once a day with the same efficacy of the separate components, but with fewer gastrointestinal effects. This is reflected in a reduction in HA1c and a lower evolution to long-term complications of T2D. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A1: Glimepiride (1mg) / Vildagliptin (50mg) / Metformin (500mg). | Experimental | Tablets, orally, once a day. Initial dose for the first 45 days of intervention. |
|
| Group B1: Glimepiride (1mg) / Vildagliptin (50mg) / Metformin (500mg) | Experimental | Tablets, orally, once a day. Initial dose for the first 45 days of intervention. |
|
| Group A2: Glimepiride (2mg) / Vildagliptin (50mg) / Metformin (1000mg) | Experimental | Tablets, orally, once a day. Dose escalation if the patients meets established criteria. |
|
| Group B2: Glimepiride (4mg) / Vildagliptin (50mg) / Metformin (1000mg) | Experimental | Tablets, orally, once a day. Dose escalation if the patients meets established criteria. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean glucose change | Compare changes in glucose between baseline, 3 and 6 months of treatment | baseline, 3 and 6 months of treatment |
| Incidence of adverse events and reactions | Description of al the adverse events and reactions presented during the study |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centro de Investigación y Avances Médicos Especializados | Cancún | Quintana Roo | 77506 | Mexico | ||
| Mérida Investigación Clínica |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31862745 | Background | 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. | |
| 26519337 | 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. |
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|
| 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. |
|
|
| (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. |
|
|
| (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. |
|
|
| baseline, 3 and 6 months of treatment |
| Mérida |
| Yucatán |
| 97125 |
| Mexico |
| Centro de Investigación Médica Aguascalientes | Aguascalientes | 20116 | Mexico |
| Oaxaca Site Management Organization SC. | Oaxaca City | 68000 | Mexico |
| Oncológico Potosino | San Luis Potosí City | 78250 | Mexico |
| 15111553 | 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. |
| 15850551 | 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. |
| 29405543 | 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. |
| 26775266 | 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. |
| 32022600 | 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. |
| 24199686 | 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. |
| 27088241 | 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. |
| 30072404 | 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. |
| 28155046 | 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. |
| 7589820 | 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. |
| 9585393 | 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. |
| 22246944 | 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. |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D000077597 | Vildagliptin |
| D008687 | Metformin |
| C057619 | glimepiride |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
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