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However, an association with weight gain has recently been suggested and several cases of diabetes mellitus have been reported with raltegravir and dolutegravir. The long-time metabolic impact of these recent molecules remains unclear.<\/jats:p><\/jats:sec>Objectives<\/jats:title>To assess if an INSTI as a third agent is statistically associated with new-onset diabetes mellitus compared with an NNRTI or a PI.<\/jats:p><\/jats:sec>Patients and methods<\/jats:title>Patients undergoing first-line combined ART (cART) without diabetes at baseline were retrospectively included from the Dat\u2019AIDS French cohort study (ClinicalTrials.gov NCT02898987). Incident diabetes mellitus was defined as a notification of new diabetes in the medical history, a glycated haemoglobin (HbA1c) level superior to 7.5% or the start of a diabetes therapy following the initiation of ART.<\/jats:p><\/jats:sec>Results<\/jats:title>From 2009 to 2017, 19\u2009462 patients were included, among which 265 cases of diabetes mellitus occurred. Multivariate and survival analyses did not highlight an increase in new-onset diabetes in patients undergoing cART with an INSTI as a third agent compared with an NNRTI or a PI. BMI &gt;30\u2009kg\/m2, age &gt;37\u2009years old (in survival analysis), black race or Hispanic ethnicity, arterial hypertension and AIDS were associated with a higher proportion of incident diabetes.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>INSTIs were not statistically associated with new-onset diabetes. 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