Back to resultsEfficacy and Safety of Metformin Glycinate Compared to Metformin Hydrochloride on the Progression of Type 2 Diabetes (COMETII)
Primary Purpose
Type 2 Diabetes
Status
Suspended
Phase
Phase 3
Locations
Mexico
Study Type
Interventional
Intervention
Metformin glycinate
Metformin Hydrochloride
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes focused on measuring Diabetes, Metformin glycinate, Metformin hydrochloride, fasting glucose
Eligibility Criteria
Inclusion Criteria:
- Subjects ≥18 years old.
- Type 2 diabetes according to ADA diagnostic criteria.
- Naive to treatment or who have previously been under oral hypoglycemic treatment (whatever it may be), as long as it has been suspended for a period of ≥6 weeks prior to the start of the study. - HbA1c ≥7.5% and <10.0%.
- In the case of women of childbearing age and with an active sexual life, the use of birth control methods is required; any of the following are accepted: barrier (male or female condom), non-hormonal intrauterine device, or bilateral tubal obstruction.
- That you agree to participate in the study and give written informed consent.
Exclusion Criteria:
- Patients with known current abuse or dependence (last 2 months) to substances such as alcohol (weekly consumption> 21 units of alcohol in men or> 14 units of alcohol in women) or recreational drugs.
- Body Mass Index <20 kg / m2 and> 35 kg / m2.
- Glomerular filtration estimated with the MDRD (Modification of Diet in Renal Disease) procedure through serum creatinine <60 ml / min / 1.72 m2.
- History of chronic liver disease or ALT (alanine aminotransferase) and / or AST (aspartate aminotransferase) ≥ 2 times the upper limit of normal, or GGT (Gamma glutamyl transpeptidase) ≥3 times the upper limit of normal.
- Chronic lung disease, causing dyspnea equivalent to a functional class ≥3 (NYHA) or requiring oxygen supplementation.
- Use of drugs that interact with biguanides.
- Other chronic diseases that limit survival or are associated with chronic inflammation such as: cancer, leukemia, lymphoma, lupus erythematosus, asthma, rheumatoid arthritis, or HIV (human immunodeficiency virus) infection.
- Pregnancy or positive pregnancy test, as well as women who are breastfeeding.
Sites / Locations
- Laboratorio Silanes, S.A. de C.V.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Group A: Metformin glycinate 1050 mg
Group B: Metformin hydrochloride 850 mg
Arm Description
Metformin glycinate 1050 mg Orally twice a day.
Metformin hydrochloride 850mg Orally twice a day.
Outcomes
Primary Outcome Measures
Change in HbA1c
Assess change in HbA1c
Secondary Outcome Measures
Changes in fasting glucose
Determine the change in fasting glucose levels
Change in the 2-hour oral glucose tolerance curve
Determine the change from baseline in the results of the 2-hour oral glucose tolerance curve
Changes to HOMA-IR (Homeostatic model assessment and Insulin resistance
Determine change in HOMA-IR
Changes in insulin levels
Determine the changes in insulin levels
Changes in leptin levels
Determine the changes in leptin levels
Changes in adipokine levels
Determine the changes in adipokine levels
Changes in proinflammatory cytokine
Determine the changes in proinflammatory cytokine
Changes in levels of MCP-1 (monocyte chemoattractant protein 1)
Determine the changes in levels of MCP-
Changes in nitric oxide levels
Determine changes in nitric oxide levels
Changes in C-reactive protein levels
Determine changes in C-reactive protein levels
Changes in body mass index
Determine changes in body mass index
Incidence of adverse events
Determine the incidence of adverse events that occurred during the study.
Full Information
NCT ID
NCT04943692
First Posted
June 21, 2021
Last Updated
June 21, 2021
Sponsor
Laboratorios Silanes S.A. de C.V.
1. Study Identification
Unique Protocol Identification Number
NCT04943692
Brief Title
Efficacy and Safety of Metformin Glycinate Compared to Metformin Hydrochloride on the Progression of Type 2 Diabetes
Acronym
COMETII
Official Title
Efficacy and Safety of Metformin Glycinate Compared to Metformin Hydrochloride on the Progression of Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Suspended
Why Stopped
Administrative decision of the investigation direction
Study Start Date
August 2021 (Anticipated)
Primary Completion Date
August 2021 (Anticipated)
Study Completion Date
August 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Laboratorios Silanes S.A. de C.V.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Phase III study to evaluate the efficacy and safety of the treatment. Two-arm, prospective, longitudinal, double-blind, multicenter randomized clinical trial.
Detailed Description
Study to evaluate the efficacy and safety of treatment at 6 and 12 months with metformin glycinate at a dose of 2100 mg / day compared to metformin hydrochloride at a dose of 1700 mg / day on the progression of type 2 diabetes. To assess the change in HbA1c from baseline to 6 and 12 months of treatment (primary endpoint) in both groups. As secondary objectives, changes in fasting glucose levels from baseline, changes in results of the oral glucose tolerance test 2h from baseline, changes in HOMA-IR from baseline, changes in insulin levels, leptin, adipokines and proinflammatory cytokines, MCP-1, nitric oxide and PCr from baseline, changes in BMI from baseline and changes in lipid profile from baseline will be evaluated. A blinded interim analysis will be performed at 6 months of patient follow-up and a final analysis. Demographic data will be analyzed with mean, standard deviation, minimum and maximum. Efficacy analyzes will be carried out in the treated population (all treated patients, ATP), made up of all randomized patients who received at least one dose of the study treatment and who have a baseline measurement and at least one subsequent measurement.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes
Keywords
Diabetes, Metformin glycinate, Metformin hydrochloride, fasting glucose
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
500 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A: Metformin glycinate 1050 mg
Arm Type
Experimental
Arm Description
Metformin glycinate 1050 mg Orally twice a day.
Arm Title
Group B: Metformin hydrochloride 850 mg
Arm Type
Active Comparator
Arm Description
Metformin hydrochloride 850mg Orally twice a day.
Intervention Type
Drug
Intervention Name(s)
Metformin glycinate
Other Intervention Name(s)
MET GLY
Intervention Description
1050 mg, tablets Administered orally, twice a day, for 12 months.
Intervention Type
Drug
Intervention Name(s)
Metformin Hydrochloride
Other Intervention Name(s)
MET HYD
Intervention Description
850 mg, tablets. Administered orally, twice a day, for 12 months.
Primary Outcome Measure Information:
Title
Change in HbA1c
Description
Assess change in HbA1c
Time Frame
Baseline, 6 and 12 months
Secondary Outcome Measure Information:
Title
Changes in fasting glucose
Description
Determine the change in fasting glucose levels
Time Frame
Baseline, 6 and 12 months
Title
Change in the 2-hour oral glucose tolerance curve
Description
Determine the change from baseline in the results of the 2-hour oral glucose tolerance curve
Time Frame
Baseline, 6 and 12 months
Title
Changes to HOMA-IR (Homeostatic model assessment and Insulin resistance
Description
Determine change in HOMA-IR
Time Frame
Baseline, 6 and 12 months
Title
Changes in insulin levels
Description
Determine the changes in insulin levels
Time Frame
Baseline, 6 and 12 months
Title
Changes in leptin levels
Description
Determine the changes in leptin levels
Time Frame
Baseline, 6 and 12 months
Title
Changes in adipokine levels
Description
Determine the changes in adipokine levels
Time Frame
Baseline, 6 and 12 months
Title
Changes in proinflammatory cytokine
Description
Determine the changes in proinflammatory cytokine
Time Frame
Baseline, 6 and 12 months
Title
Changes in levels of MCP-1 (monocyte chemoattractant protein 1)
Description
Determine the changes in levels of MCP-
Time Frame
Baseline, 6 and 12 months
Title
Changes in nitric oxide levels
Description
Determine changes in nitric oxide levels
Time Frame
Baseline, 6 and 12 months
Title
Changes in C-reactive protein levels
Description
Determine changes in C-reactive protein levels
Time Frame
Baseline, 6 and 12 months
Title
Changes in body mass index
Description
Determine changes in body mass index
Time Frame
Baseline, 6 and 12 months
Title
Incidence of adverse events
Description
Determine the incidence of adverse events that occurred during the study.
Time Frame
Baseline, 6 and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subjects ≥18 years old.
Type 2 diabetes according to ADA diagnostic criteria.
Naive to treatment or who have previously been under oral hypoglycemic treatment (whatever it may be), as long as it has been suspended for a period of ≥6 weeks prior to the start of the study. - HbA1c ≥7.5% and <10.0%.
In the case of women of childbearing age and with an active sexual life, the use of birth control methods is required; any of the following are accepted: barrier (male or female condom), non-hormonal intrauterine device, or bilateral tubal obstruction.
That you agree to participate in the study and give written informed consent.
Exclusion Criteria:
Patients with known current abuse or dependence (last 2 months) to substances such as alcohol (weekly consumption> 21 units of alcohol in men or> 14 units of alcohol in women) or recreational drugs.
Body Mass Index <20 kg / m2 and> 35 kg / m2.
Glomerular filtration estimated with the MDRD (Modification of Diet in Renal Disease) procedure through serum creatinine <60 ml / min / 1.72 m2.
History of chronic liver disease or ALT (alanine aminotransferase) and / or AST (aspartate aminotransferase) ≥ 2 times the upper limit of normal, or GGT (Gamma glutamyl transpeptidase) ≥3 times the upper limit of normal.
Chronic lung disease, causing dyspnea equivalent to a functional class ≥3 (NYHA) or requiring oxygen supplementation.
Use of drugs that interact with biguanides.
Other chronic diseases that limit survival or are associated with chronic inflammation such as: cancer, leukemia, lymphoma, lupus erythematosus, asthma, rheumatoid arthritis, or HIV (human immunodeficiency virus) infection.
Pregnancy or positive pregnancy test, as well as women who are breastfeeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillermo Fanghänel Salmón, M.D
Organizational Affiliation
Clinica integral del paciente diabético y obeso
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Manuel González Ortiz, M.D
Organizational Affiliation
Instituto de terapéutica experimental y clínica (INTEC)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joel Rodríguez Saldaña, M.D
Organizational Affiliation
Resultados médicos, desarrollo e investigación SC. (REMEDI)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
María L Sánchez Aldana Robles, M.D
Organizational Affiliation
Investigación Biomédica para el Desarrollo de Fármacos, S.A de C.V. (IBIOMED-GDL)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Francisco G Padilla Padilla, M.D
Organizational Affiliation
Independent
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jorge V Yamamoto Cuevas, M.D
Organizational Affiliation
Clínica Villa Coapa La Vereda S.C.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Edmundo D Ríos Mejía, M.D
Organizational Affiliation
Investigación Biomédica para el Desarrollo de Fármacos S.A. de C.V. (IBIOMED-AGS)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Luis M Román Pintos, M.D
Organizational Affiliation
Hospital Hispanos S.A. de C.V.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Víctor Bohórquez López, M.D
Organizational Affiliation
Oaxaca Site Management Organization SC. (Red OSMO)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Santiago P Ramírez Díaz, M..D
Organizational Affiliation
Centro de Investigación Médica Aguascalientes (Red OSMO)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
José De la Cruz Tun Pech, M.D
Organizational Affiliation
Mérida Investigación Clínica (Red OSMO)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fernando J Lavalle González, M.D
Organizational Affiliation
Servicio de endocrinología Hospital Univertsitario, UANL
Official's Role
Principal Investigator
Facility Information:
Facility Name
Laboratorio Silanes, S.A. de C.V.
City
Mexico City
ZIP/Postal Code
11000
Country
Mexico
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
18955637
Citation
Alexander GC, Sehgal NL, Moloney RM, Stafford RS. National trends in treatment of type 2 diabetes mellitus, 1994-2007. Arch Intern Med. 2008 Oct 27;168(19):2088-94. doi: 10.1001/archinte.168.19.2088.
Results Reference
background
PubMed Identifier
2862087
Citation
U.K. prospective diabetes study. II. Reduction in HbA1c with basal insulin supplement, sulfonylurea, or biguanide therapy in maturity-onset diabetes. A multicenter study. Diabetes. 1985 Aug;34(8):793-8.
Results Reference
background
PubMed Identifier
17145742
Citation
Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006 Dec 7;355(23):2427-43. doi: 10.1056/NEJMoa066224. Epub 2006 Dec 4. Erratum In: N Engl J Med. 2007 Mar 29;356(13):1387-8.
Results Reference
background
PubMed Identifier
7895460
Citation
Hermann LS, Schersten B, Melander A. Antihyperglycaemic efficacy, response prediction and dose-response relations of treatment with metformin and sulphonylurea, alone and in primary combination. Diabet Med. 1994 Dec;11(10):953-60. doi: 10.1111/j.1464-5491.1994.tb00253.x.
Results Reference
background
PubMed Identifier
20388897
Citation
Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010 Apr 14;303(14):1410-8. doi: 10.1001/jama.2010.405.
Results Reference
background
PubMed Identifier
9742977
Citation
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65. Erratum In: Lancet 1998 Nov 7;352(9139):1558.
Results Reference
background
PubMed Identifier
18784090
Citation
Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10.
Results Reference
background
PubMed Identifier
19959591
Citation
Tzoulaki I, Molokhia M, Curcin V, Little MP, Millett CJ, Ng A, Hughes RI, Khunti K, Wilkins MR, Majeed A, Elliott P. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ. 2009 Dec 3;339:b4731. doi: 10.1136/bmj.b4731.
Results Reference
background
PubMed Identifier
18955635
Citation
Selvin E, Bolen S, Yeh HC, Wiley C, Wilson LM, Marinopoulos SS, Feldman L, Vassy J, Wilson R, Bass EB, Brancati FL. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med. 2008 Oct 27;168(19):2070-80. doi: 10.1001/archinte.168.19.2070.
Results Reference
background
PubMed Identifier
15787679
Citation
Johnson JA, Simpson SH, Toth EL, Majumdar SR. Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes. Diabet Med. 2005 Apr;22(4):497-502. doi: 10.1111/j.1464-5491.2005.01448.x.
Results Reference
background
PubMed Identifier
19307526
Citation
Kooy A, de Jager J, Lehert P, Bets D, Wulffele MG, Donker AJ, Stehouwer CD. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med. 2009 Mar 23;169(6):616-25. doi: 10.1001/archinternmed.2009.20.
Results Reference
background
PubMed Identifier
7306436
Citation
Tucker GT, Casey C, Phillips PJ, Connor H, Ward JD, Woods HF. Metformin kinetics in healthy subjects and in patients with diabetes mellitus. Br J Clin Pharmacol. 1981 Aug;12(2):235-46. doi: 10.1111/j.1365-2125.1981.tb01206.x.
Results Reference
background
PubMed Identifier
12130709
Citation
Wang DS, Jonker JW, Kato Y, Kusuhara H, Schinkel AH, Sugiyama Y. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J Pharmacol Exp Ther. 2002 Aug;302(2):510-5. doi: 10.1124/jpet.102.034140.
Results Reference
background
PubMed Identifier
8165821
Citation
Wilcock C, Bailey CJ. Accumulation of metformin by tissues of the normal and diabetic mouse. Xenobiotica. 1994 Jan;24(1):49-57. doi: 10.3109/00498259409043220.
Results Reference
background
PubMed Identifier
8743335
Citation
Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 1996 May;30(5):359-71. doi: 10.2165/00003088-199630050-00003.
Results Reference
background
PubMed Identifier
7601013
Citation
Dunn CJ, Peters DH. Metformin. A review of its pharmacological properties and therapeutic use in non-insulin-dependent diabetes mellitus. Drugs. 1995 May;49(5):721-49. doi: 10.2165/00003495-199549050-00007.
Results Reference
background
PubMed Identifier
3359923
Citation
Vidon N, Chaussade S, Noel M, Franchisseur C, Huchet B, Bernier JJ. Metformin in the digestive tract. Diabetes Res Clin Pract. 1988 Feb 19;4(3):223-9. doi: 10.1016/s0168-8227(88)80022-6.
Results Reference
background
PubMed Identifier
11012555
Citation
Marathe PH, Wen Y, Norton J, Greene DS, Barbhaiya RH, Wilding IR. Effect of altered gastric emptying and gastrointestinal motility on metformin absorption. Br J Clin Pharmacol. 2000 Oct;50(4):325-32. doi: 10.1046/j.1365-2125.2000.00264.x.
Results Reference
background
PubMed Identifier
18484913
Citation
Pacanowski MA, Hopley CW, Aquilante CL. Interindividual variability in oral antidiabetic drug disposition and response: the role of drug transporter polymorphisms. Expert Opin Drug Metab Toxicol. 2008 May;4(5):529-44. doi: 10.1517/17425255.4.5.529.
Results Reference
background
PubMed Identifier
10576523
Citation
Wiernsperger NF, Bailey CJ. The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms. Drugs. 1999;58 Suppl 1:31-9; discussion 75-82. doi: 10.2165/00003495-199958001-00009.
Results Reference
background
PubMed Identifier
9428831
Citation
Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study. Am J Med. 1997 Dec;103(6):483-90. doi: 10.1016/s0002-9343(97)00252-0.
Results Reference
background
PubMed Identifier
17026483
Citation
Schimmack G, Defronzo RA, Musi N. AMP-activated protein kinase: Role in metabolism and therapeutic implications. Diabetes Obes Metab. 2006 Nov;8(6):591-602. doi: 10.1111/j.1463-1326.2005.00561.x.
Results Reference
background
PubMed Identifier
11756340
Citation
Standeven KF, Ariens RA, Whitaker P, Ashcroft AE, Weisel JW, Grant PJ. The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation. Diabetes. 2002 Jan;51(1):189-97. doi: 10.2337/diabetes.51.1.189.
Results Reference
background
PubMed Identifier
10656230
Citation
Gregorio F, Ambrosi F, Manfrini S, Velussi M, Carle F, Testa R, Merante D, Filipponi P. Poorly controlled elderly Type 2 diabetic patients: the effects of increasing sulphonylurea dosages or adding metformin. Diabet Med. 1999 Dec;16(12):1016-24. doi: 10.1046/j.1464-5491.1999.00201.x.
Results Reference
background
PubMed Identifier
11225659
Citation
Pavlovic D, Kocic R, Kocic G, Jevtovic T, Radenkovic S, Mikic D, Stojanovic M, Djordjevic PB. Effect of four-week metformin treatment on plasma and erythrocyte antioxidative defense enzymes in newly diagnosed obese patients with type 2 diabetes. Diabetes Obes Metab. 2000 Aug;2(4):251-6. doi: 10.1046/j.1463-1326.2000.00089.x.
Results Reference
background
PubMed Identifier
14502106
Citation
Beisswenger P, Ruggiero-Lopez D. Metformin inhibition of glycation processes. Diabetes Metab. 2003 Sep;29(4 Pt 2):6S95-103. doi: 10.1016/s1262-3636(03)72793-1.
Results Reference
background
PubMed Identifier
16026361
Citation
Yamanouchi T, Sakai T, Igarashi K, Ichiyanagi K, Watanabe H, Kawasaki T. Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed Type 2 diabetes. Diabet Med. 2005 Aug;22(8):980-5. doi: 10.1111/j.1464-5491.2005.01656.x.
Results Reference
background
PubMed Identifier
20040656
Citation
Brown JB, Conner C, Nichols GA. Secondary failure of metformin monotherapy in clinical practice. Diabetes Care. 2010 Mar;33(3):501-6. doi: 10.2337/dc09-1749. Epub 2009 Dec 29.
Results Reference
background
Learn more about this trial
Efficacy and Safety of Metformin Glycinate Compared to Metformin Hydrochloride on the Progression of Type 2 Diabetes
We'll reach out to this number within 24 hrs