Switching from another GLP-1 receptor agonist to semaglutide may lead to reductions of ~0.3% to ~0.8%-points in and ~2% to ~4% in body weight with semaglutide 1.0 mg.
The potency-adjusted total effective GLP-1RA concentration increased after switching treatments.
Temporary slight deteriorations in HbA1c were noted when switching to semaglutide 0.25 mg.
Switching to semaglutide from liraglutide, dulaglutide, or exenatide extended-release is associated with further reductions in HbA1c and body weight.
Higher initial doses of semaglutide may prevent initial deterioration in outcomes.
Simplified
AIMS: Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue approved for the treatment of type 2 diabetes. The impact of switching treatment from another GLP-1 receptor agonist (GLP-1RA) to semaglutide was investigated by analyses of exposure-response models.
METHODS: and body weight time-course models were developed, using up to 30 weeks of observations from four trials in the semaglutide phase 3 programme. Given the recommended dosing for each GLP-1RA, pharmacokinetic profiles were simulated based on published population pharmacokinetic models and exposure was adjusted by the relative potencies to ensure that model predictions matched the effects observed in clinical trials. After 26 weeks of simulated treatment with liraglutide, dulaglutide or exenatide extended-release, simulated semaglutide treatment was initiated 1 day after the last once-daily dose of liraglutide and 1 week after the last once-weekly doses of dulaglutide or exenatide extended-release.
RESULTS: The potency-adjusted total effective GLP-1RA concentration increased after switching from another GLP-1RA to semaglutide and was associated with reductions ranging from ~0.3% to ~0.8%-points for HbA1c and from ~2% to ~4% for body weight with semaglutide 1.0 mg. Temporary slight deteriorations in HbA1c were observed after switching to semaglutide 0.25 mg from liraglutide 1.2/1.8 mg or dulaglutide 1.5 mg.
CONCLUSIONS: Exposure-response modelling suggests that switching to semaglutide from liraglutide, dulaglutide or exenatide extended-release results in further reductions in HbA1c and body weight. Initial slight deterioration in outcome values when switching to semaglutide 0.25 mg could be avoided by initiating semaglutide treatment at a higher dose.
Key numbers
~0.3% to ~0.8%
Reduction Range
Predicted reductions in after switching to semaglutide 1.0 mg.
~2% to ~4%
Body Weight Reduction Range
Predicted reductions in body weight after switching to semaglutide 1.0 mg.
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