Prediabetes, HIV-infection Nutritional, Metabolic, Endocrine Prediabetes, HIV-infection
Conditions
Interventions
Metformin extended release at a dose of 2000mg per day and matching placebo. The follow up period will be three years. Eligible patients will be randomised using permuted blocks in a 1:1 ratio, strati
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current participant inclusion criteria as of 12/12/2022: 1. Adult HIV-positive persons on antiretroviral therapy (ART) for at least 6 months and considered stable on treatment (i.e. in regular attendance for care). Considered by the clinical team to be in routine care with a plasma viral load of less than 1000 copies per ml taken within the last 12 months. 2. Either impaired fasting glucose (=6.1 to =6.9 mmol/L) and/or impaired glucose tolerance at 2 hours (=7.8 to 12 months 4. Written informed consent Previous participant inclusion criteria: 1. HIV-positive and stable on the same antiretroviral therapy for at least 6-months 2. Attending the HIV clinic regularly for at least 6 months 3. Impaired fasting glucose of between 6.1 to 6.9 mmol/L and/or impaired glucose tolerance at 2 hours of 7.8 to 11.10 mmol/L 4. Planning to remain in the area for > 1 year 5. Willing to provide written informed consent
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 12/12/2022: 1. Pregnant women 2. Patients who were participants of the META Phase II study 3. Renal disease or renal dysfunction (eGFR180/110 mmHg, haemoglobin<6.5g/dL for women or haemoglobin <7.0g/dL for men (grade 3); white cell count <1.5 x 109 cells/mm3(grade 3) and any baseline liver function derangements at grade 4 according to DAIDS criteria. Previous participant exclusion criteria: 1. Pregnant women 2. Renal disease or renal dysfunction (eGFR < 45) 3. Signs and symptoms of any form of acute metabolic acidosis including lactic acidosis and diabetic ketoacidosis 4. Other acute conditions with: 4.1. The potential to alter renal function including: dehydration, severe infection or shock 4.2. The potential to cause tissue hypoxia including decompensated heart failure, respiratory failure, recent myocardial infarction, shock 5. Congestive heart failure requiring pharmacological treatment 6. Clinical evidence of liver disease 7. Evidence of alcoholism or acute alcohol intoxication 8. Known hypersensitivity to metformin or any excipients associated with the preparation (in this case: Magnesium stearate, sodium carboxymethylcellulose, hypromellose) 9. Other acute conditions requiring hospital admission
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 17/01/2025: Incidence of diabetes, measured over up to a 48-month follow-up period. The diagnosis of diabetes will be made using an oral glucose tolerance test, which will be conducted annually _____ Previous primary outcome measure: Incidence of diabetes, measured over a 36-month follow-up period. The diagnosis of diabetes will be made using an oral glucose tolerance test, which will be conducted annually | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Prevalence and incidence of glycaemia related complications, measured at the start and end of the study, and at any point during follow up where clinically indicated. The study will assess for the following diabetes related complications: 1.1. Retinopathy using retinal photography 1.2. Neuropathy using the Neuropathy Disability Score and the Diabetic Neuropathy Symptom Score 1.3. Nephropathy using serial assessment of eGFR 2. Time to diabetes-free survival, measured at the end of study follow up 3. Cost consequences. Costs associated with lost productivity, and health services and social care resource use will be collected, during and at the end of the study 4. Health-related quality-of-life, measured using EuroQol EQ-5D and 12-item Short Form-12 5. Cost-effectiveness, measured at the end of study follow up. Information on costs will be collected using economic patient questionnaires to measure patients related costs (out-of-pocket expenses, costs associated with lost productivity) as well as costs of all resources used by patients (health service and social care resource use costs). The collected costs and health outcomes will be used to estimate possible cost savings and/or cost-effectiveness of metformin (i.e., cost changes per patient, cost per diabetes case prevented, and QALYs gained). | — |
Countries
Tanzania
Outcome results
None listed