medwireNews: People with type 2 diabetes who take a weekly dose of 2.0 mg semaglutide experience significantly greater reductions in glycated hemoglobin (HbA1c) and body weight than those who take the standard 1.0 mg dose, show the results of the phase 3 study.
In addition, the two doses of the glucagon-like peptide (GLP) -1 receptor agonist had “a similar safety profile,” reported Juan Frias (National Research Institute, Los Angeles, California, USA) at the virtual ADA 81st Scientific Sessions.
Frias stated that about 20-30% of people taking the currently approved weekly doses of 0.5 mg and 1.0 mg semaglutide in the previous SUSTAIN studies did not have HbA1c levels below 7% (53 mmol / mol) and the SUSTAIN FORTE investigators hypothesized that treatment at the higher dose of 2.0 mg / week would result in “more patients achieving treatment goals.”
Click through for a quick guide to the SUSTAIN studies
To test this theory, 961 adults with type 2 diabetes and an average baseline HbA1c of 8.9% (74 mmol / mol) were randomly given subcutaneous semaglutide once a week at a maintenance dose of 1.0 mg or 2, 0 mg for 28 weeks, a 12-week dose escalation phase in which all participants began with a dose of 0.25 mg / week, which was doubled every 4 weeks until the maintenance dose was reached. All participants received a stable dose of metformin, while approximately 53% also received sulfonylureas.
In the test product estimation analysis – which reflects the effect of the intended use of the drug – the average HbA1c values in the semaglutide arm at 2.0 mg decreased by 2.2 percentage points from baseline up to week 40 and by 1.9 percentage points in the 1st 0 mg arm, a significant difference. Participants treated with the 2.0 mg dose versus the 1.0 mg dose also achieved significantly higher HbA1c levels below 7 at week 40 at rates of 67.6% versus 57.5% , 0%.
Similarly, the mean HbA1c reduction in the treatment policy estimate analysis reflecting the effect of prescribing the drug was, with an average reduction of 2.1 and
Frias said there was a “very similar pattern” of results for the confirmatory secondary endpoint, weight loss. In the study’s product estimation analysis, participants in the 2.0 mg group experienced a significantly greater decrease in body weight than those in the 1.0 mg group, at 6.9 versus 6.0 kg versus a baseline average of 99 , 3 kg. The corresponding decreases in the treatment policy estimate analysis were 6.4 kg and 5.6 kg.
Overall, adverse events (AEs) occurred in 56.8% and 52.3% of the participants in the 2.0 and 1.0 mg groups, while the corresponding 4.4% and 5.2% serious AE occurred. The rates of gastrointestinal AEs were higher in the 2.0 mg arm (34.0 vs. 30.8%), which was “largely driven by an increased incidence of decreased appetite” with the higher dose, Frias said.
Decreased appetite was reported in 6.1% of participants receiving the 2.0 mg dose compared with 3.8% of participants in the 1.0 mg arm; the respective rates of nausea, diarrhea, and vomiting were 14.4% versus 14.6%, 9.4% versus 8.8%, and 7.7% versus 6.7%.
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Scientific meetings of the ADA; 25-29 June 2021
