# Metformin Treatment and Immune Reconstitution in People With HIV and Type 2 Diabetes: A Matched Retrospective Study

**Authors:** Tintin Bäckdahl, Pontus Hedberg, Jan Vesterbacka, Christina Carlander, Anders Sönnerborg, Piotr Nowak

PMC · DOI: 10.1093/ofid/ofaf110 · 2025-02-24

## TL;DR

This study found no significant immune benefits from metformin in people with HIV and type 2 diabetes over two years.

## Contribution

The study provides new evidence on metformin's lack of immune reconstitution effects in a matched HIV and T2DM cohort.

## Key findings

- No significant difference in CD4 T-cell count change between metformin-treated and control groups.
- No significant difference in CD4/CD8 ratio change between the two groups.
- Subgroup analyses showed no immune benefits in individuals with low baseline CD4 counts.

## Abstract

Despite effective antiretroviral treatment (ART), HIV infection is associated with immune dysfunction and inflammation. Metformin has shown beneficial immunological and anti-inflammatory effects, including in people with HIV (PWH). We studied the potential association between metformin treatment and immune reconstitution in PWH.

We conducted a retrospective cohort study set in Stockholm, Sweden. PWH with T2DM who initiated metformin treatment after at least 2 years on effective ART (exposed individuals) and metformin-naïve PWH (controls) were matched in a 1:1 ratio based on age, sex, baseline immune status, and duration of ART. Outcomes included mean values of CD4 cell counts and CD4/CD8 ratios from 1.5 years to 3.5 years after compared with 2 years before the exposed individual started metformin treatment (index date).

Among 1332 PWH, 43 metformin-exposed individuals (median age, 48 years; 11 years since start of ART) with T2DM and 43 nondiabetic controls (median age, 47 years; 11 years since start of ART) were included in the matched analyses. The median (interquartile range) change in CD4 T-cell count was 35 (−21 to 125) cells/μL among exposed individuals and 48 (−18 to 100) cells/μL among controls (P = .96). The corresponding numbers were 0.10 (0.03 to 0.20) and 0.08 (0.02–0.16) for CD4/CD8 ratio (P = .18). No differences were observed in subgroup analyses of PWH with low CD4 T-cell counts and CD4/CD8 ratios.

No significant differences in immune reconstitution were observed between metformin-treated individuals and matched controls over the 2-year follow-up period.

We observed no significant differences in immune reconstitution (measured by CD4 T cell count and CD4/CD8 ratio) between metformin treated individuals and matched controls over a 2-year follow-up period.

## Linked entities

- **Chemicals:** metformin (PubChem CID 4091)
- **Diseases:** Type 2 Diabetes (MONDO:0005148), T2DM (MONDO:0005148)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}
- **Diseases:** Type 2 Diabetes (MESH:D003924), inflammation (MESH:D007249), HIV infection (MESH:D015658), immune dysfunction (MESH:D007154)
- **Chemicals:** Metformin (MESH:D008687)
- **Species:** Human immunodeficiency virus 1 (no rank) [taxon 11676]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11950528/full.md

---
Source: https://tomesphere.com/paper/PMC11950528