# P-243. Association Between Integrase inhibitor Use with Insulin Resistance and Incident Diabetes Mellitus in Persons Living with HIV: A Systematic Review and Meta-analysis

## TL;DR

This study finds that integrase inhibitors, a type of HIV treatment, are not generally linked to higher diabetes risk, though exceptions exist in African populations.

## Contribution

A systematic review and meta-analysis of integrase inhibitors' association with diabetes and insulin resistance in people with HIV.

## Key findings

- INSTI therapy was associated with a lower risk of incident diabetes compared to non-INSTIs and NNRTIs.
- INSTIs showed a reduced diabetes risk in ART-naïve patients and studies with longer follow-up.
- INSTIs were not linked to increased HOMA-IR changes compared to other ARTs, except in African populations.

## Abstract

Integrase based anti-retroviral therapy is currently the most used first- and second-line therapy for the treatment of HIV. Case reports and series of patients developing accelerated hyperglycaemia after initiating integrase inhibitors have been reported. Whether integrase inhibitors (INSTIs) are associated with a higher risk of incident type 2 diabetes mellitus than other antiretroviral therapies (ART) needs to be established.

Risk of incident diabetes mellitus and hyperglycemia with exposure to integrase inhibitors

Sub-analysis for the risk of incident diabetes mellitus and hyperglycemia with exposure to integrase inhibitors

Medline, Embase, Web of Science and ClinicalTrials.gov registries were searched for studies published between 1st January 2000 to 15th June 2022. Eligible studies reported incident diabetes mellitus or mean changes in insulin resistance measured by homeostatic model index (HOMA-IR) in patients on INSTIs compared to other ARTs. We performed random-effects meta-analyses to obtain pooled relative risks (RR) with 95% confidence intervals (CI).

Mean changes in HOMA-IR from baseline in INSTIs group compared to overall non-INSTIs, NNRTIs and PIs groups.

A total of 16 studies were pooled, 13 studies meta-analysed for incident diabetes with a patient population of 72,404 and 3 for changes in HOMA-IR. INSTI therapy was associated with a lower risk of incident diabetes in 13 studies (relative risk [RR] 0.80, 95% CI 0.67-0.96, I2=29%), of which 8 randomised controlled trials demonstrated a 22% reduced risk (RR 0.88, 95% CI 0.81-0.96, I2=0%). INSTIs had a lower risk compared to non-nucleoside reverse transcriptase inhibitors (NNRTI) (RR 0.75, 95% CI 0.63-0·89, I2=0%), but similar to protease inhibitor (PI)-based therapy (RR 0.78, 95% CI 0.61-1.01, I2=27%). The risk was lower in studies with longer follow-up (RR 0.70, 95% CI 0.53-0.94, I2=24%) and among ART naïve patients (RR 0.78, 95% CI 0.65-0.94, I2=3%) but increased in African populations (RR: 2.99, 95% CI: 2.53-3.54, I2=0%). INSTIs were associated with an insignificant increase in mean HOMA-IR from baseline compared to non-INSTIs (0.78, 95%CI -0.15 – 1.70) and PIs (0.90, 95%CI -0.90 – 2.69) and to NNRTIs (0.17, 95%CI -0.44 – 0.79)

Exposure to INSTIs was not associated with increased risk of diabetes mellitus, except in African populations which were largely under-represented in the meta-analysis. Stratified analyses suggested reduced risk among ART naïve patients and studies with longer follow-up.

Robert C. Bollinger, Jr., MD, MPH, [SCENE] Health: Advisor/Consultant|[SCENE] Health: Board Member|[SCENE] Health: Stocks/Bonds (Private Company)|Merck: Advisor/Consultant|miDiagnostics: Co-inventor of IP owned by Johns Hopkins University|miDiagnostics: Eligible for equity and royalty payments received by Johns Hopkins University