Weight loss differences seen with fixed vs flexible insulin, GLP-1RA regimens
medwireNews: Patients initiating a flexible combination of basal insulin plus a glucagon-like peptide (GLP)-1 receptor agonist (RA) have similar improvements in glycemic control to those initiating a fixed combination, but with greater weight loss, real-world study data show.
“The greater improvement in body weight in the flexible group was likely attributable to the higher GLP-1RA doses and the lower [basal insulin] doses than in the fixed group,” report the GLP-1REWIN researchers in Diabetes, Obesity and Metabolism.
The retrospective study included data for 609 patients on basal insulin for type 2 diabetes who initiated a fixed (n=131) or flexible (n=478) basal insulin/GLP‐1RA combination between 2010 and 2018.
At baseline, the average basal insulin doses were 20.1 and 22.1 units in the fixed and flexible groups, increasing to 26.3 and 22.3 units, respectively, after a median 5.7 months of follow-up.
In the fixed group, all participants received liraglutide as their GLP-1RA at a starting dose of 0.72 mg, increasing to 0.94 mg. In the flexible group the starting doses were 1.29 mg and 1.37 mg for liraglutide and dulaglutide, respectively, increasing to 1.47 mg and 1.50 mg at follow-up.
After propensity score matching of 42 baseline variables, there was a similar reduction in glycated hemoglobin (HbA1c) levels in the fixed (from 8.9% to 8.1%) and flexible (from 8.9% to 8.4%) groups, resulting in a non-significant treatment difference of 0.26%.
By contrast, bodyweight decreased by a significantly greater 1.2 kg in the flexible group relative to the fixed group (2.5 vs 1.2 kg), but after accounting for a significant 5.1-unit greater increase in basal insulin dose in the fixed group, the difference in weight loss between the two groups was no longer significant, at 0.90 kg.
The researchers found no significant differences between the fixed and flexible groups for the reduction in fasting plasma glucose (26.2 vs 16.5 mg/dL) or systolic blood pressure (0.9 vs 2.8 mmHg), but note that the estimated total treatment cost per patient was significantly lower in the fixed group, at € 878.8 versus 1096.0 (US$ 983.7 vs 1226.8), or € 36.9 vs 44.8 ($ 41.3 vs 50.1) per patient per week.
The team observed similar results in a fully adjusted multivariable analysis that included all patients with endpoint data, with no significant difference between the two groups in HbA1c but a significant 1.52 kg greater reduction in body weight among patients in the flexible group.
Discussing their findings, Gian Paolo Fadini (University of Padova, Italy) and co-authors speculate that “the reasons underlying the choice of a fixed or flexible combination may have driven the differential outcome.”
“For instance, a flexible add-on of GLP-1RA to [basal insulin] could have been chosen if the need for full-dose GLP-1RA was prioritized over intensification of [basal insulin] dose,” they write.
By Laura Cowen
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