The prevalence of obesity is rising worldwide, both in low- and high-income countries, including people with HIV (PWH). Semaglutide's efficacy in achieving weight loss in obese PWH is still unexplored. The aim of this study is to assess the efficacy and safety of semaglutide in achieving greater weight loss compared to diet and excercise alone in obese PWH and to explore the effect of semaglutide on the immune function, markers of immune activation, viral reservoir, markers of glucose and lipid metabolism and gut microbiome.
A randomised, controlled, parallel-group, open-label study comparing treatment with the GLP-1 analogue semaglutide in combination with lifestyle interventions to lifestyle interventions alone in obese PWH. The study will enroll HIV-1 infected patients ≥ 18 years with BMI ≥30kg/m2 or BMI ≥27kg/m2 and hypertension, dyslipidaemia or type 2 diabetes mellitus. Primary objective: To assess the efficacy of semaglutide as an adjunct to diet and exercise in achieving greater weight loss in obese PWH as compared to diet and exercise alone. Secondary objectives: * To explore the effect of semaglutide on markers of immune function and HIV viral reservoirs in obese PWH. * To explore the effect of semaglutide on markers of glucose and lipid metabolism in obese PWH. * To explore the effect of semaglutide on markers of inflammation and gut microbial translocation in obese PWH. * To assess the safety of semaglutide in obese PWH on stable ART.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Semaglutide 0.25 mg subcutaneously once weekly for 4 weeks, then Semaglutide 0.5 mg subcutaneously once weekly for 4 weeks, then Semaglutide 1 mg subcutaneously once weekly for 20 weeks. Total treatment duration 28 weeks.
Diet and exercise advice for 40 weeks
Mater Misericordiae University Hospital
Dublin, Dublin, Ireland
RECRUITINGChanges in total body weight (in Kg)
Between-group differences in percent change from baseline to week 28 in total body weight
Time frame: 28 weeks
Proportion of subjects not achieving 5% weight loss from baseline to week 16
Between-group differences in number of subjects who do not achieve a 5% weight loss (in Kg) from baseline to week 16
Time frame: 16 weeks
Changes in numbers and function of immune cell subsets
Between-group differences in percent change from baseline in numbers and functions of immune cells subsets (NK cells, MAIT cells, T-cells and Monocytes) as assessed through flow cytometry in a single assay
Time frame: 40 weeks
Changes in quantified viral reservoir in peripheral blood mononuclear cells (PBMCs)
Between-group differences in percent change from baseline in HIV pro-viral DNA and cell-associated RNA (CA-RNA), measured in PBMCs (copies/mL)
Time frame: 40 weeks
Changes in gut microbiome composition in stool samples
Between-group differences in percent change from baseline in gut microbiome composition (% prevalence of different microbial species) as assessed through molecular techniques in stool samples
Time frame: 40 weeks
Changes in parameters of glucose metabolism in blood samples
Between-group differences in percent change from baseline in blood glucose levels (in mmol/L), HbA1c (in mmol/mol) and insulin levels (in pmol/L)
Time frame: 40 weeks
Changes in parameters of lipid metabolism
Between-group differences in percent change from baseline in lipid profile: total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (all in mmol/L)
Time frame: 40 weeks
Proportion of subjects reporting any adverse event
Between-group differences in the number of subjects reporting any type of adverse event, including serious adverse events and suspected unexpected serious adverse reactions
Time frame: 40 weeks
Changes in bone mineral density (BMD) and total body composition
Between-group differences in percent change from baseline in lumbar spine and hip BMD and total body composition (% fat mass and lean mass) as assessed through DXA scan
Time frame: 40 weeks
Changes in liver stiffness
Between-group differences in percent change from baseline in liver stiffness (measured in kPa) as assessed thourgh liver elastography
Time frame: 40 weeks
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