Exploring the Relationship Between Dolutegravir and Diabetes Using Routine Data of Patients on Anti-Retroviral Treatment in a High HIV Prevalence Setting.

Abstract

Background: Dolutegravir has been associated with excessive weight gain and type 2 diabetes mellitus (T2DM) The study aimed to describe the incidence and prevalence of type 2 diabetes mellitus in a cohort of patients exposed and non-exposed to dolutegravir containing antiretroviral therapy in Eswatini.

Methods: We conducted a retrospective observational study using routinely collected data from electronic medical records for adults aged ≥25years active on antiretroviral therapy in two of the country's regions between 01 October 2018 and 31 August 2025. Included patients were adults (≥25 years) active on antiretroviral therapy with no prior diagnosis of diabetes mellitus. The primary outcome was a documented diagnosis of type 2 diabetes mellitus among dolutegravir initiators- patients who started antiretroviral therapy on a dolutegravir-based regimen; dolutegravir transitioners- patients previously on a non-dolutegravir regimen who transitioned to a dolutegravir-based regimen; and non- dolutegravir users- patients that were never exposed to dolutegravir. Multiple imputation was used to handle missing data in body mass index and antiretroviral therapy duration. Descriptive statistics were used to describe patient characteristics, and Poisson log link regression was used to compute incidence risk ratios.

Results: A total of 102330 patients were analyzed (21938 in dolutegravir initiators group, 73967 in dolutegravir transitioners group and 6425 in non-dolutegravir users group). The participant mean age was 43.7±11.7years, the mean duration on antiretroviral therapy was 9.4±3.9years and mean body mass index (BMI) was 27.5±6.2 kg/m². The overall prevalence of type 2 diabetes was 2.0% (1.2% among dolutegravir initiators; 2.3% among dolutegravir transitioners and 1.4% among non-dolutegravir users) and the overall incidence rate was 3.6 cases per 1000person-years [Non-dolutegravir Users-6.2 per 1000person-years), Dolutegravir Transitioners (3.6 per 1000person-years) and Dolutegravir Initiators (2.9 per 1000person-years)]. After adjusting for age, BMI, and duration on antiretroviral therapy, Dolutegravir Initiators (aIRR=0.4) and Dolutegravir Transitioners (aIRR=0.4) had a lower risk than Non-Dolutegravir Users.

Conclusion: There was a protective relationship for developing type 2 diabetes mellitus for patients on dolutegravir-based regimens in comparison to non-dolutegravir regimens. All patients commencing antiretroviral therapy should have baseline and ongoing blood glucose monitoring as a critical component in the management of HIV.