DURATION-8 combines antidiabetic medications to promising effect
medwireNews: Combining a glucagon-like peptide-1 (GLP-1) receptor agonist with a sodium-glucose co-transporter-2 (SGLT2) inhibitor improves glycaemic control more than either therapy alone in patients with Type 2 diabetes, shows the DURATION-8 trial.
The 685 participants all had glycated haemoglobin (HbA1c) levels between 8% and 12%, despite at least 2 months of metformin treatment (which they continued in addition to the study drugs).
From a baseline average of 9.3%, patients randomly assigned to take exenatide reduced their HbA1c levels by 1.6% during 28 weeks of treatment, while those assigned to receive dapagliflozin reduced theirs by 1.4%.
But patients assigned to take both medications achieved a significantly greater reduction in HbA1c levels, of 2.0%, report Juan Frías (National Research Institute, Los Angeles, California, USA) and co-researchers in The Lancet Diabetes & Endocrinology.
The authors of an accompanying commentary, Michael Nauck and Juris Meier (St Josef Hospital, Bochum, Germany), observe that this reduction is “numerically far less than additive”, but explain that “because the absolute glucose-lowering efficacy of a given glucose-lowering drug diminishes with lower baseline HbA1c, a second drug will generally seem less effective.”
However, they describe as “disappointing” the finding that only 45% of patients in the combination group achieved HbA1c levels below 7% by the study end, although this was significantly greater than the 27% and 19% who achieved it with exenatide and dapagliflozin, respectively.
Patients taking both medications also had significantly greater reductions in fasting plasma glucose, by 2.30 versus 1.19 and 1.46 mmol/L with exenatide and dapagliflozin, respectively, and in postprandial plasma glucose, at 4.83 versus 3.31 and 3.41 mmol/L.
The commentators say that trials of a GLP-1 receptor agonist plus an SGLT2 inhibitor “have long been awaited” because the contrasting mechanisms suggest that the combination could be beneficial.
“The obvious expectations were that the combination would lower HbA1c and bodyweight more than either component alone, and that no episodes of hypoglycaemia would be provoked unless combined with sulfonylureas or insulin”, they write.
And the combination did have a beneficial impact on bodyweight, with 33% of patients in the combination group losing at least 5% of their bodyweight, compared with 14% and 20% of those taking exenatide and dapagliflozin, respectively. They also had a greater reduction in systolic blood pressure, by 4.2 versus 1.3 and 1.8 mmHg.
There were no hypoglycaemic episodes meeting the researchers’ criteria for major or minor hypoglycaemia (both required blood glucose <3.0 mmol/L). Other hypoglycaemic events were more common in the combination therapy group, but were low overall, at 3%, compared with 1% in both monotherapy groups, and most were rated as mild.
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