AWARD-10 supports GLP-1 receptor agonist–SGLT2 inhibitor combination
medwireNews: The AWARD-10 findings show significantly improved glycemic control in patients with type 2 diabetes who add the glucagon-like peptide (GLP)-1 receptor agonist dulaglutide to any sodium-glucose cotransporter (SGLT)2 inhibitor.
During 24 weeks of treatment, glycated hemoglobin (HbA1c) levels fell by 1.34% among the 142 patients randomly assigned to take dulaglutide 1.5 mg and by 1.21% among the 141 taking dulaglutide 0.75 mg. Over the same period, HbA1c fell by an average of 0.54% in a further 140 patients taking placebo, giving significant differences of 0.79% and 0.66% for the 1.5 mg and 0.75 mg doses, respectively, versus placebo.
The patients were aged around 57 years, on average, with a diabetes duration of around 9 years and a starting HbA1c level of just over 8%. All patients had been taking an SGLT2 inhibitor, most commonly dapagliflozin or empagliflozin, for at least 3 months, and the vast majority were also taking metformin.
Adverse event rates were similar for the three groups, except that patients taking dulaglutide had more nausea and diarrhea than those taking placebo.
The findings support those of DURATION-8, published in 2016, although the trials differ in that patients in DURATION-8 started on metformin monotherapy, to which they added exenatide, dapagliflozin, or both. The combination proved significantly more effective than either treatment alone.
In AWARD-10, reported in The Lancet Diabetes & Endocrinology by Zvonko Milicevic (Eli Lilly and Company, Vienna, Austria) and colleagues, significantly more patients taking dulaglutide achieved an HbA1c target of 7%, at 71% and 60% for the 1.5 and 0.75 mg doses versus 32% for placebo, and they lost more weight, at a respective 3.1, 2.6, and 2.1 kg.
And significantly more dulaglutide-treated patients achieved the composite endpoint of HbA1c below 7% without weight gain or symptomatic hypoglycemia, at 50–61%, versus 26% of the placebo group.
In a linked commentary, Christophe De Block (University of Antwerp, Belgium) notes that although the benefits of GLP-1 receptor agonists and SGLT2 inhibitors are clear, their use in clinical practice is often restrained by financial considerations.
“Thus real-world prescription habits lag behind the evidence, with only about 7% of patients with type 2 diabetes being treated with SGLT2 inhibitors,” he observes.
De Block outlines some remaining questions about combination treatment, such as its use in patients with little residual beta-cell function and in the elderly, and its effect on long-term complications such as cardiovascular and renal events.
But he concludes that AWARD-10 and DURATION-8 “introduce a new era in diabetes management.”
He says the findings “will help to guide clinicians to make therapeutic decisions and will hopefully open the door for more patients who could benefit from this novel combination early in the course of their disease.”
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