PRuDENTE; Diabetes Prevention Via Exercise, Nutrition and Treatment

Study Overview
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Brief Summary
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The PRuDENTE study proposes to assess if metformin therapy a viable, efficient and cost-effective intervention to decrease the incidence of type 2 diabetes (DMT2) in adult subjects with obesity and pre-diabetes in Mexico City. Half of the individuals recruited will receive as intervention, metformin and lifestyle modification therapy and the other half will receive only lifestyle modification therapy.

Detailed Description
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Diabetes in Mexico is considered a national emergency given its high prevalence, incidence, mortality and costs. Mexico has one of the highest prevalence of diabetes; in only 6 years (2000 to 2006) this prevalence increased from 7.5% to 14.4%. In 2015, 151 deaths per 100,000 inhabitants occurred in Mexico due to diabetes complications. Metformin is a hypoglycemia drug and it´s the first line medication for the treatment of type 2 diabetes.There is currently a significant amount of evidence that metformin administration reduces the progression from pre-diabetes to diabetes and, despite its monotherapy being less effective than lifestyle changes, the good biosafety profile and low cost have made it the drug of choice in a joint treatment. The PRuDENTE study proposes to perform this intervention in a real environment in the clinics of the first level of care of the Ministry of Health of the Government of Mexico City, in order to provide evidence about the cost-effectiveness of metformin as a public health intervention for the prevention of diabetes.

Official Title
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Public Healthcare Systems and Diabetes Prevention Among People of Mexican Origin: The PRuDENTE Initiative of Mexico City.

Conditions
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Diabetes Mellitus, Type 2, Prediabetic State

Intervention / Treatment
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* Drug: Metformin
* Behavioral: Lifestyle intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Having received primary care in the chosen health center (ideally two or more visits to that clinic in the prior year). Subscribers to Seguro Popular ( Mexican national health insurance) Body mass index >=30 kg / m2 Results of fasting serum glucose with values for pre-diabetes diagnosis (glucose between 100 and 125 mg / dl) Optional: Family history of DMT2 (1st grade relative). Previous diagnosis of hypertension or dyslipidaemia. Have received antihypertensive medication and / or for cholesterol / lipids. History of gestational diabetes mellitus. Exclusion Criteria: Renal insufficiency (Glomerular Filtration Rate (GFR) <30 ml/min). Known hepatic impairment or altered liver enzymes (aspartate aminotransferase (AST) AST or alanine aminotransferase (ALT) three times above normal values) Active alcoholism or drug addiction Allergies or previous known intolerance to exercise or metformin. Current pregnancy. Plans to leave the area in the next three years. Previous diagnosis of type 2 diabetes mellitus

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Primary health care clinics will be allocated to one of the two arms of the intervention. A) lifestyle modification, B) Metformin and lifestyle modification
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lifestyle Intervention<br>The prediabetic individuals from the primary care centres that belong to this arm, will receive only recommendations for lifestyle modifications (physical activity and diet). | Behavioral: Lifestyle intervention<br>* The patient will received recommendations to modify their diet and increase their physical activity every three months towards prevention of diabetes<br>|
| Active Comparator: Metformin<br>The prediabetic individuals from the primary care centres that belong to this arm, will receive metformin treatment and lifestyle modifications recommendations (physical activity and diet). | Drug: Metformin<br>* The patient will received metformin 1 tablet of 850mg every 12 hrs besides lifestyle modification recommendations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diabetes. measured by HbA1c and Fasting blood glucose (FBG) | We define type 2 diabetes (T2D) as either FBG 100-125 mg/dl or HbA1c of >= 6.5% | 3 years | 
| Lifestyle modifications by decreasing adiposity indicators | We will evaluate this by : weight in Kg, height in mts. They also be combined to report BMI/m2, and waist circumference | Will be evaluated every 3 months during the 36 month period | 
| Caloric intake | From food-frequency questionnaires. | Every 3 months during the 36 month period | 
| Physical Activity | Expresses ad the average metabolic equivalents (METs)-hours/week | Every 3 months during the 36 month period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implementation process outcomes at the clinic level. Using a questionnaire | Assess the implementation process outcomes at the clinic-, clinician- and patient-levels that will explain the observed effectiveness, and enable future efforts to adapt and disseminate the intervention model across other primary care settings. A questionnaire will be develop to assess the feasibility and limitations for the longterm implementation of this intervention | 5 years | 
| Implementation process outcomes at the clinician level. Using a questionnaire | A questionnaire will be develop to assess the limitations of recruitment at the clinic . As well as to evaluate the feasibility of continuing this intervention in outside patients. | 5 years | 
| Implementation process outcomes patient level. Assess via questionnaire | Assess the implementation process at the patient-levels using a questionnaire that show data regarding adherence to treatment and lifestyle modifications. | 5 years | 
| Cost-utility of Metformin. Measured using cost per QALYS | Analyse the cost-utility of the implementation of this intervention in primary-care health. Using direct and indirect health-care cost data. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, prevention, metformin, Mexico City