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Changes in weight and glycemia after initiation of integrase
strand transfer inhibitors among people with HIV and diabetes
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Overall, participants treated with INSTIs experienced modestly worse glycemic outcomes than those treated with NNRTIs. Although the mean change in HbA1c did not differ significantly between the two groups, INSTI users had a higher risk of the composite outcome of glucose-lowering therapy intensification or an increase in HbA1c of at least 0.5% compared with NNRTI users. In contrast, the risk of glycemic outcomes was similar between the INSTI and protease inhibitor groups.
INSTI users tended to initiate treatment later in the study period than NNRTI or protease inhibitor users, which could introduce bias from evolving clinical practices in diabetes management. While we adjusted for calendar time of ART initiation (i.e. time of study entry), individual cardiometabolic profiles, and concomitant use of glucose-lowering agents, these adjustments may not have fully eliminated such bias.
AIDS Aug 2026
Download the PDF here
Download the PDF here
Objective:
Evaluate the impact of initiating integrase strand transfer inhibitor (INSTI) - vs. nonnucleoside reverse transcriptase inhibitor (NNRTI) - or protease inhibitor-based regimens on weight and glycemia among people with HIV (PWH) and type 2 diabetes.
Design:
Cohort study.
Methods:
From multisite HIV cohorts in the United States and Canada (2007-2022), we identified PWH with diabetes who newly initiated INSTI-based, NNRTI-based, or protease inhibitor-based therapy. We used inverse probability of treatment-weighted (IPTW) generalized linear models to compare changes in weight and hemoglobin A1c (HbA1c) at approximately 12 months after antiretroviral therapy (ART) initiation. We assessed time to at least 5% weight gain and to glucose-lowering therapy augmentation or HbA1c increase at least 0.5 percentage points with IPTW Cox regression.
Results:
Among 1279 PWH with diabetes, 548 initiated an INSTI-based regimen, 511 an NNRTI-based regimen, and 220 a protease inhibitor-based regimen.
Compared with NNRTI users, INSTI users had greater adjusted mean weight gain [2.1 kg; 95% confidence interval (CI), 1.1-3.1], while the difference in HbA1c change was modest (0.2%; 95% CI, 0.0-0.5); both changes were similar between INSTI and protease inhibitor users.
INSTI users had higher risk of at least 5% weight gain [adjusted hazard ratio (aHR), 1.35; 95% CI, 1.15-1.59] and glucose-lowering therapy augmentation or HbA1c increase at least 0.5% (aHR, 1.19; 95% CI, 1.02-1.41) compared with NNRTI users although similar risk vs. protease inhibitor users.
Conclusion:
Among PWH with diabetes, initiating INSTIs conferred modestly greater weight gain and worse glycemic outcomes vs. NNRTIs, but outcomes comparable to PIs, which is recognized for adverse metabolic effects. These findings inform the metabolic implications of INSTIs and support clinical monitoring after ART initiation.
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