The META Trial

The challenge

An estimated 26 million people are living with HIV in sub-Saharan Africa, 20 million of whom are receiving antiretroviral therapy. At the same time, around 25 million people in the region are affected by type 2 diabetes, a number that is projected to increase to 60 million by 2050. Around half a million people in the region already die from diabetes every year.

These are not independent epidemics. People living with HIV are at higher risk of developing type 2 diabetes. In HIV clinical trial participants in Tanzania, for example, 15% were found to have type 2 diabetes, despite never having been diagnosed. This rate is significantly higher than in the general population.

Type 2 diabetes is a progressive condition that is preceded by an asymptomatic stage, pre-diabetes, which is associated with impaired glucose control. Pre-diabetes is highly predictive of type 2 diabetes, and early detection provides an opportunity to intervene to reduce the risk of full-blown disease. Although type 2 diabetes can be prevented by the adoption of healthier lifestyles, in practice, lifestyle interventions are ineffective unless accompanied by intensive individual support, which would be impractical in sub-Saharan Africa settings.

The project

The META Trial project has been pursuing an alternative strategy, based on the use of metformin, a commonly used and highly effective diabetes drug, which also appears able to slow progression from pre-diabetes.

Funded through the EDCTP2 programme, the META project has been conducting a trial in Tanzania to assess whether metformin prevents pre-diabetes progression in people living with HIV. The trial planned to recruit more than 2,000 patients and follow them for three years.

However, the study was badly affected by the COVID-19 pandemic, which led to delays in regulatory approvals and to the decentralisation of HIV care, which slowed recruitment. Global Health EDCTP3 funding will enable the project to complete recruitment, full follow-up of participants and data analysis, generating the largest body of trial evidence on pre-diabetes prevention in sub-Saharan Africa to date.

The project has proceeded with close engagement with policymakers from Tanzania to ensure that it delivers policy-relevant evidence and has an immediate impact on national policymaking.

Impact

The META Trial project will generate key data on metformin use to prevent type 2 diabetes in people living with HIV. It will:

• Provide global and national policymakers with definitive evidence on the efficacy of metformin for diabetes prevention in this critical group.
• Generate clinical, cost-effectiveness and qualitative data to inform national decision-making.
• Provide important insights into how diabetes and other non-communicable disease care can be integrated with HIV management. 

The META Trial project received a national UK award, the Times Higher Education award for International Partnership of the Year, for ‘creating an equitable partnership that led to a step change in research’. Results from other studies suggest that the risk of diabetes could be cut by more than a third by metformin, delivering a significant reduction in the disease burden associated with HIV infection.