PIONEER 8: Semaglutide add-on lowers HbA1c in type 2 diabetes insulin users
medwireNews: Oral semaglutide significantly reduces glycated hemoglobin (HbA1c) and bodyweight versus placebo in people with type 2 diabetes that is poorly controlled on insulin, results of the PIONEER 8 study show.
Bernard Zinman (University of Toronto, Ontario, Canada) and co-investigators say that the glucagon-like peptide (GLP)-1 receptor agonist “may help reduce concerns over weight gain and hypoglycemia associated with insulin use and may have an insulin sparing effect at [higher doses].”
The study, presented as a poster at the 79th ADA Scientific Sessions in San Francisco, California, USA, randomly assigned 731 people with type 2 diabetes uncontrolled on insulin either alone or in combination with metformin to receive once daily oral semaglutide at a dose of 3 mg (n=184), 7 mg (n=182), or 14 mg (n=181), or placebo (n=184) for 52 weeks.
Participants were encouraged to reduce their total daily insulin dose by 20% during the first 8 weeks of the study and were allowed to increase it to no more than the dose they were using at randomization until week 26. From weeks 26 to 52 the total daily insulin dose was freely adjustable.
At week 26, the reduction in HbA1c from a baseline of 8.2% was significantly greater with the 3 mg, 7 mg, and 14 mg doses of semaglutide than with placebo, at 0.6%, 0.9%, and 1.3%, respectively, versus 0.1%.
There were also significantly greater reductions in bodyweight with all three semaglutide doses relative to placebo, at 1.4 kg, 2.4 kg, and 3.7 kg, respectively, versus 0.4 kg.
Furthermore, the results for both outcomes were maintained until week 52.
The researchers also found that mean daily insulin dose was significantly lower with semaglutide 7 mg and 14 mg than with placebo at week 26 and with all semaglutide doses by week 52.
The rate of severe or blood glucose-confirmed hypoglycemia did not differ between the patients receiving semaglutide (26.0–28.3%) and those receiving placebo (29.3%), but a higher proportion in the semaglutide groups discontinued treatment due to adverse events (7.1–13.3% vs 2.7% with placebo).
Gastrointestinal disorders, and nausea in particular, were the most common adverse events that led to semaglutide discontinuation.
Speaking to medwireNews, Zinman said that as the first oral GLP-1 inhibitor under investigation, semaglutide “is going to be very important for physicians and a lot of patients.”
He continued: “Obviously it requires a little bit of care in how you take it. It’s not your standard pop a pill in but it’s not an injection and so I think having both options is very, very important, particularly in a primary care setting where they’re not used to prescribing injectable therapies.”
He added that he believes semaglutide is equivalent to other therapies used in patients with uncontrolled glycemia on insulin.
“If a patient is on insulin and they’re not meeting their targets you can do one of two things: Increase the dose of insulin or go to multiple daily injections which we know is going to be associated with weight gain and hypoglycemia.
“Or you can add another therapy [oral semaglutide] which is complementary because it reduces the dose of insulin and reduces weight with no difference in hypoglycemia, and better A1c – it’s a no brainer.”
By Laura Cowen
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