medwireNews: The SUSTAIN 2 findings show that the glucagon-like peptide (GLP)-1 analog semaglutide produces better glycemic control than the dipeptidyl peptidase-4 inhibitor sitagliptin in patients achieving inadequate control with metformin, thiazolidinediones, or both.
Patients given once-weekly injections of the GLP-1 analog (plus daily oral placebo) also had significantly larger reductions in bodyweight during the 56 weeks of treatment, achieving 4.3 and 6.1 kg reductions with semaglutide 0.5 and 1.0 mg, respectively, compared with an average 1.9 kg reduction for those taking daily sitagliptin 100 mg (plus weekly placebo injection).
“Semaglutide seems to be a promising treatment option for participants with type 2 diabetes,” write Bo Ahrén (Lund University, Sweden) and co-researchers in The Lancet Diabetes & Endocrinology.
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They note that the drug has fared well against other established antidiabetic medications in the SUSTAIN trials reported so far, as well as reducing cardiovascular outcomes in high-risk patients.
In SUSTAIN 2, average baseline glycated hemoglobin (HbA1c) levels were 8.0% in both semaglutide groups and 8.2% in the sitagliptin group. During follow-up, these fell by an absolute 1.3% in the 409 patients taking semaglutide 0.5 mg and by 1.6% in the 409 taking 1.0 mg, respectively. Both these reductions were significantly larger than the 0.5% reduction achieved by the 407 patients taking sitagliptin 100 mg.
The corresponding reductions in fasting plasma glucose were 2.1 and 2.6 mmol/L versus 1.1 mmol/L, and again the differences between the semaglutide and sitagliptin groups were statistically significant. The proportions of patients achieving an HbA1c level below 7.0% without experiencing severe or blood-confirmed symptomatic hypoglycemia were a respective 63% and 74% versus 27%.
Systolic blood pressure fell significantly more among patients taking semaglutide than those taking sitagliptin. By contrast, pulse rate rose more, significantly so in the semaglutide 1.0 mg group, but the researchers note that this should be viewed in the context of the improved cardiovascular outcomes seen in SUSTAIN 6.
Adverse events occurred in similar proportions of all treatment groups, but more patients discontinued semaglutide than sitagliptin because of adverse events, at 8–10% versus 3%. This was mostly because of gastrointestinal events, which occurred in 40–44% versus 24% and led to discontinuation in 7–8% versus 1%.
“Although the trial was sufficiently long in duration to assess the primary outcome of HbA1c, it was short in view of the chronic nature of diabetes and also underpowered to assess differences between treatments for rare safety issues, such as alterations of the exocrine pancreas and thyroid,” the team observes.
“Longer and more extensive trial data will be needed to further assess the safety of semaglutide.”
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