Short-acting exenatide makes little difference to glycemia in type 1 diabetes
medwireNews: Short-acting exenatide “does not seem to have a future” as a standard adjunct treatment in people with type 1 diabetes, say the MAG1C investigators.
Filip Knop (Herlev and Gentofte Hospital, Hellerup, Denmark) and co-researchers tested the theory that the reduced gastric emptying rate produced by a glucagon-like peptide (GLP)-1 receptor agonist would lead to improved prandial glycemic control, and therefore an overall improvement in glycated hemoglobin (HbA1c), in people with type 1 diabetes.
But during 26 weeks of treatment, this benefit did not emerge, they report in The Lancet Diabetes & Endocrinology.
The 52 people who were randomly assigned to receive exenatide took an initial dose of 5 µg within 1 hour before each main meal, escalating to 10 µg after 2 weeks. Their HbA1c decreased from 66.8 mmol/mol (8.3%) at baseline to 63.2 mmol/mol (7.9%) at 26 weeks, and the corresponding values for the 53 people taking placebo were 65.9 mmol/mol (8.2%) and 64.2 mmol/mol (8.0%).
The baseline-adjusted decrease of 3.2 mmol/mol (0.3%) seen with exenatide was not significantly greater than the 2.1 mmol/mol (0.2%) decrease seen with placebo. There were also no differences for any secondary endpoints assessed from self-monitored blood glucose or masked continuous glucose monitoring (the latter for 6 days prior to randomization, week 4, and week 26).
Side effects were “predominantly gastrointestinal,” say the researchers, and there was no significant difference in hypoglycemia rates between the treatment groups.
As expected, exenatide reduced prandial insulin needs, by an average of 9.0 U/day versus placebo by week 26. An additional benefit was an average 4.4 kg reduction in bodyweight relative to the placebo group, from a baseline of 89.7 kg.
In a linked commentary, Michael Nauck and Juris Meier, both from Ruhr-University Bochum in Germany, suggest that the weight loss potential with an adjunct GLP-1 receptor agonist could be greater in people with type 1 than type 2 diabetes, “perhaps related to the down-titration in (bolus) insulin or the higher dose of the GLP-1 receptor agonists in relation to bodyweight in lower-weight patients with type 1 diabetes.”
But they say that the results of MAG1C overall, in line with previous studies, “do not uniformly support the use of GLP-1 receptor agonists in patients with type 1 diabetes.”
However, the commentators note that glucose control in people with type 1 diabetes is a highly individualized process. In addition to this, adding an adjunct medication – which will reduce glycemia – necessitates adjustments to the dose and timing of insulin that can promote increased glycemia.
This “delicate balance” could “explain the overall minor effects” of adjunct medications in people with type 1 diabetes, they say, in part because the full benefits and risks “probably cannot be captured by a single primary endpoint.” Nauck and Meier contrast this with the robust effects of add-ons to insulin therapy in people with type 2 diabetes.
They therefore conclude: “Although the reported beneficial effects might not be convincing enough to support a treatment indication for GLP-1 receptor agonists as an adjunct to insulin treatment in type 1 diabetes, such therapeutic approaches might still be helpful, if carefully tested individually, in selected patients.”
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