Prediabetic StatePhase 3NCT04134650
Effect of Low Dose Combination of Linagliptin + Metformin to Prevent Diabetes
A Phase 3 study testing Linagliptin + metformin and Metformin in people with Prediabetic State and Insulin Resistance, run by Universidad de Guanajuato at 1 site in Mexico.
Trial summary
Type 2 diabetes is a chronic disease that has reached global epidemic proportions due to the growing number of patients in all countries; It has become the disease that causes more chronic and acute complications to patients, unfortunately, when the diagnosis of type 2 diabetes is made patients are identified at very… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Prediabetic State, Insulin Resistance
- What is being tested?
- Linagliptin + metformin and Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteMexico
- Study dates
- 1 Sep 2019to 1 Jul 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with prediabetes, defined for the existence of one or both of the following conditions: 1) impaired fasting glucose (Fasting glucose between 100 and 125 mg/dL), 2) impaired glucose tolerance (Glucose between 140 and 199 mg/dL at the 2 hours of the Oral Glucose Tolerance test (OGTT)
- Patients who accept to participate in the study and sign the informed consent letter.
Who cannot join
- Patients with diagnosed Type 2 Diabetes Mellitus previously or detected during the OGTT
- Patients in actual treatment or during the last 3 months with metformin, pioglitazone or another antidiabetic drug, including insulin.
- Serum creatinine > 1.6 mg/dL
- Hypertriglyceridemia very high (>500 mg/dL)
- Pregnant women
- Altered arterial hypertension (Systolic > 180 mmHg or Diastolic >105 mmHg)
- Excessive alcohol intake, acute or chronic
- Medications or medical conditions that affect glucose homeostasis (thiazides, beta blockers, glucocorticoids for systemic use, weight-reducing drugs or anorexigenics, Cushing's syndrome, Thyrotoxicosis.
Trial locations and contacts
1 site in 1 country.
Mexico1 site, 1 recruiting
- Recruiting
Universidad de Guanajuato
León, Guanauato, 37670
Rodolfo Guardado-Mendoza, MDPhD, 4772674900 ext. 3683, guardamen@gmail.com
Elizabeth Rodríguez-Guzmán, MD, 4772674900 ext. 3683, elirodg@hotmail.com
About this study
Official title: Effect of Low Dose Combination of Linagliptin and Metformin to Improve Pancreatic Beta Cell Function, Insulin Resistance and Cardiovascular Function in Patients With Prediabetes and Overweight/Obesity: Randomizer Clinical Trial
Type 2 diabetes is a chronic disease that has reached global epidemic proportions due to the growing number of patients in all countries; It has become the disease that causes more chronic and acute complications to patients, unfortunately, when the diagnosis of type 2 diabetes is made patients are identified at very advanced stages of the disease.
For all the above, the best strategies will be those that are aimed at early stages of the disease, and the investigators are convinced that the use the combination of drugs with additive pathophysiological effect plus cardiovascular protection in early stages, will have better results, lasting and with greater results impact on the natural history of the disease that throws measures that may have an applicability in clinical practice, in order to contribute to the control of this pathology. Therefore, the combination of medications with different mechanisms of action, in low doses, could be a useful strategy not only to prevent type 2 diabetes, but also to prevent macro and microvascular complications early. The goal of this clinical trial is to evaluate the effect of low doses of linagliptin + metformin vs metformin alone on physiopathological parameters, such as glucose metabolism, insulin resistance, insulin secretion and pancreatic beta cell function in patients with impaired fasting glucose plus impaired glucose tolerance, during 12 months.
Read the detailed description
The main goal of this clinical trial is to compare the effect of two different treatments during 12 months:
- Lifestyle modification program + metformin 1700mg every 24 hours.
- Lifestyle modification program + linagliptin (2.5mg) and metformin (1700mg) every 24 hours. on the following parameters, after 12 months of treatment:
- Glucose metabolism, evaluated by the oral glucose tolerance
- Insulin resistance, evaluated by the oral glucose tolerance in 100% of the patients
- Insulin secretion, evaluated by the oral glucose tolerance in 100% of the patients
- Pancreatic beta cell function, evaluated by the oral glucose tolerance in 100% of the patients
- Cardiovascular function, evaluated by ejection fraction measurement, diastolic and systolic preloads measured by standard echocardiography.
All the patients will have a basal evaluation with an oral glucose tolerance test, lipid profile, body composition. After the basal evaluation, if the patients result with prediabetes (FASTING IMPAIRED GLUCOSE/IMPAIRED GLUCOSE TOLERANCE) and have at least 2 risk factors, they will be invited to the intervention phase where they will be randomized to one of the two treatment groups.
Patients will have a follow-up visit every month to review the adherence to the lifestyle modification program and to the medication. After 6 months, patients will repeat the same evaluation performed as the basal evaluation.
- Conditions
- Prediabetic State, Insulin Resistance
- Being tested
- Linagliptin + metformin, Metformin
- Keywords
- Prediabetes
- Medical subject headings
- Prediabetic State, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linagliptin + metforminCombination product
Also called low doses of Linagliptin + metformin
Linagliptin-Metformin 2.5/1700mg daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling
MetforminDrug
Metformin 1700mg daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling
| Study group | Role | What they receive |
|---|---|---|
| Linagliptin + Metformin plus lifestyle | Experimental | Patients are randomized to receive for 12 months Linagliptin 2.5mg + metformin 1700mg every 24 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week. Receives: Combination Product: Linagliptin + metformin |
| Metformin plus lifestyle | Active comparator | Patients are randomized to receive for 12 months Metformin 1700mg every 24 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from basal fasting and 2 hours glucose levels during the oral glucose tolerance test at 12 months
Fasting and post-2 hours glucose values (mg/dl) during the oral glucose tolerance test
Measured: 12 months
Secondary outcomes (2)
Change from basal pancreatic beta cell function at 12 months
Evaluated with the Disposition index (DI), obtained from measurements of glucose and insulin during the oral glucose tolerance test. A higher value in the DI meas a better pancreatic beta cell function. There are not minimum and maximum levels
Measured: 12 months
Change from basal insulin sensitivity at 12 months
Insulin sensitivity evaluated with the Matsuda Index, obtained with the insulina and glucose measurements during the oral glucose tolerance test. Matsuda index is reported in arbitrary units, and a higher value means a better insulin sensitivity. There are not minimum and maximum levels
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2019
- Study start1 Sep 2019
- Primary completion30 Jun 2020 (estimated)
- Study completion1 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Prediabetic StateStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 ratio allocation
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidad de Guanajuato
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Regional de Alta Especialidad del Bajio
- Responsible party
- Principal investigator, Rodolfo Guardado Mendoza, Universidad de Guanajuato
- Investigators
- Rodolfo Guardado-Mendoza, MDPhD, Principal investigator, Universidad de Guanajuato
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04134650
- Sponsor's protocol ID
- CI/HRAEB/2018/0018
- Status last verified
- Oct 2019
- First submitted
- 18 Oct 2019
- Last updated
- 25 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schulz LO, Bennett PH, Ravussin E, Kidd JR, Kidd KK, Esparza J, Valencia ME. Effects of traditional and western environments on prevalence of type 2 diabetes in Pima Indians in Mexico and the U.S. Diabetes Care. 2006 Aug;29(8):1866-71. doi: 10.2337/dc06-0138.
PubMed 16873794DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care. 1992 Mar;15(3):318-68. doi: 10.2337/diacare.15.3.318.
PubMed 1532777Faerch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia. 2009 Sep;52(9):1714-23. doi: 10.1007/s00125-009-1443-3. Epub 2009 Jul 10.
PubMed 19590846Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577-80. doi: 10.1177/29.4.6166661.
PubMed 6166661King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. doi: 10.2337/diacare.21.9.1414.
PubMed 9727886Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998 Jul 23;339(4):229-34. doi: 10.1056/NEJM199807233390404.
PubMed 9673301
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Low Dose Combination of Linagliptin and Metformin to Improve Pancreatic Beta Cell Function, Insulin Resistance and Cardiovascular Function in Patients With Prediabetes and Overweight/Obesity: Randomizer Clinical Trial
- ClinicalTrials.gov ID
- NCT04134650
- Acronym / sponsor ID
- CI/HRAEB/2018/0018
- Conditions
- Prediabetic State, Insulin Resistance
- Keywords
- Prediabetes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Universidad de GuanajuatoUniversity, hospital or other
- Collaborators
- Hospital Regional de Alta Especialidad del Bajio
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 30 Jun 2020 (estimated)
- Study completion
- 1 Jul 2020 (estimated)
- First posted
- 22 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Type 2 diabetes is a chronic disease that has reached global epidemic proportions due to the growing number of patients in all countries; It has become the disease that causes more chronic and acute complications to patients, unfortunately, when the diagnosis of type 2 diabetes is made patients are identified at very advanced stages of the disease.
For all the above, the best strategies will be those that are aimed at early stages of the disease, and the investigators are convinced that the use the combination of drugs with additive pathophysiological effect plus cardiovascular protection in early stages, will have better results, lasting and with greater results impact on the natural history of the disease that throws measures that may have an applicability in clinical practice, in order to contribute to the control of this pathology. Therefore, the combination of medications with different mechanisms of action, in low doses, could be a useful strategy not only to prevent type 2 diabetes, but also to prevent macro and microvascular complications early. The goal of this clinical trial is to evaluate the effect of low doses of linagliptin + metformin vs metformin alone on physiopathological parameters, such as glucose metabolism, insulin resistance, insulin secretion and pancreatic beta cell function in patients with impaired fasting glucose plus impaired glucose tolerance, during 12 months.
Detailed description
The main goal of this clinical trial is to compare the effect of two different treatments during 12 months:
- Lifestyle modification program + metformin 1700mg every 24 hours.
- Lifestyle modification program + linagliptin (2.5mg) and metformin (1700mg) every 24 hours. on the following parameters, after 12 months of treatment:
- Glucose metabolism, evaluated by the oral glucose tolerance
- Insulin resistance, evaluated by the oral glucose tolerance in 100% of the patients
- Insulin secretion, evaluated by the oral glucose tolerance in 100% of the patients
- Pancreatic beta cell function, evaluated by the oral glucose tolerance in 100% of the patients
- Cardiovascular function, evaluated by ejection fraction measurement, diastolic and systolic preloads measured by standard echocardiography.
All the patients will have a basal evaluation with an oral glucose tolerance test, lipid profile, body composition. After the basal evaluation, if the patients result with prediabetes (FASTING IMPAIRED GLUCOSE/IMPAIRED GLUCOSE TOLERANCE) and have at least 2 risk factors, they will be invited to the intervention phase where they will be randomized to one of the two treatment groups.
Patients will have a follow-up visit every month to review the adherence to the lifestyle modification program and to the medication. After 6 months, patients will repeat the same evaluation performed as the basal evaluation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 1:1 ratio allocation
| Arm | Type | Receives |
|---|---|---|
| Linagliptin + Metformin plus lifestyle | Experimental | Combination Product: Linagliptin + metforminPatients are randomized to receive for 12 months Linagliptin 2.5mg + metformin 1700mg every 24 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week. |
| Metformin plus lifestyle | Active comparator | Drug: MetforminPatients are randomized to receive for 12 months Metformin 1700mg every 24 hours. The start of the dose in this group will be gradual so that at the month of treatment the patient can be with the full doses. Together with this, patients will receive a lifestyle modification program seeking to reduce 5-7% of body weigh and increase physical activity to 90-150min/week. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with prediabetes, defined for the existence of one or both of the following conditions: 1) impaired fasting glucose (Fasting glucose between 100 and 125 mg/dL), 2) impaired glucose tolerance (Glucose between 140 and 199 mg/dL at the 2 hours of the Oral Glucose Tolerance test (OGTT)
- Patients who accept to participate in the study and sign the informed consent letter.
Key exclusion criteria (8 listed)
- Patients with diagnosed Type 2 Diabetes Mellitus previously or detected during the OGTT
- Patients in actual treatment or during the last 3 months with metformin, pioglitazone or another antidiabetic drug, including insulin.
- Serum creatinine > 1.6 mg/dL
- Hypertriglyceridemia very high (>500 mg/dL)
- Pregnant women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Linagliptin + metforminAlso: low doses of Linagliptin + metforminLinagliptin-Metformin 2.5/1700mg daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling | Combination product | Linagliptin + Metformin plus lifestyle |
| MetforminMetformin 1700mg daily plus a lifestyle modification program based on nutritional assesment, physical activity prescription and general counseling | Drug | Metformin plus lifestyle |
Primary outcome
Change from basal fasting and 2 hours glucose levels during the oral glucose tolerance test at 12 months
Time frame: 12 months
Fasting and post-2 hours glucose values (mg/dl) during the oral glucose tolerance test
2 secondary outcomes
Change from basal pancreatic beta cell function at 12 months
Time frame: 12 months
Change from basal insulin sensitivity at 12 months
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2019.
- Background: PubMed 16873794Schulz LO, Bennett PH, Ravussin E, Kidd JR, Kidd KK, Esparza J, Valencia ME. Effects of traditional and western environments on prevalence of type 2 diabetes in Pima Indians in Mexico and the U.S. Diabetes Care. 2006 Aug;29(8):1866-71. doi: 10.2337/dc06-0138.
- Background: PubMed 1532777DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care. 1992 Mar;15(3):318-68. doi: 10.2337/diacare.15.3.318.
- Background: PubMed 19590846Faerch K, Borch-Johnsen K, Holst JJ, Vaag A. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes? Diabetologia. 2009 Sep;52(9):1714-23. doi: 10.1007/s00125-009-1443-3. Epub 2009 Jul 10.
- Results publication: PubMed 6166661Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577-80. doi: 10.1177/29.4.6166661.
- Results publication: PubMed 9727886King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31. doi: 10.2337/diacare.21.9.1414.
- Results publication: PubMed 9673301Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998 Jul 23;339(4):229-34. doi: 10.1056/NEJM199807233390404.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rodolfo Guardado-Mendoza, MDPhD principal investigator
Universidad de Guanajuato
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Linagliptin + metformin and Metformin in people with Prediabetic State and Insulin Resistance, run by Universidad de Guanajuato at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rodolfo Guardado-Mendoza, MDPhD (011524772672000 ext. 1701, guardamen@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from basal fasting and 2 hours glucose levels during the oral glucose tolerance test at 12 months (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04134650, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2019.