Comparable glycaemic control with dulaglutide vs insulin glargine for T2D patients with CKD
The GLP-1* receptor agonist dulaglutide confers comparable glycaemic control with greater albuminuria reduction and less eGFR** decline compared with insulin glargine in patients with type 2 diabetes (T2D) and moderate-to-severe chronic kidney disease (CKD), when both are used in combination with the human insulin analogue lispro, according to the AWARD-7*** study presented at the EASD Annual Meeting 2017 in Lisbon, Portugal.
“The results hold up in CKD stage 4, just as it did in CKD [stage] 3, very similar to what was published in the LEADER trial last week,” said Dr Katherine Tuttle of the University of Washington in Spokane, Washington, US.
Equivalent reductions in HbA1c levels from baseline at week 26, the primary endpoint, were seen in both the high- and low-dose dulaglutide arms compared with the insulin glargine arm (-1.2 percent and -1.1 percent for dulaglutide 1.5 mg and 0.75 mg, respectively, vs -1.1 percent for insulin glargine; one-sided p<0.001 for noninferiority for both comparisons). [EASD 2017, abstract OP #02]
Likewise, similar proportion of patients in the dulaglutide arms achieved a HbA1c goal of <8.0 percent (<64 mmol/mol) as those in the insulin glargine arm (78.3 percent and 72.6 percent vs 75.3 percent).
“The effects were maintained up to 52 weeks of treatment,” said Tuttle, noting that the mean HbA1c reduction from baseline and the proportion of patients achieving target HbA1c were similar among the treatment arms at 52 weeks.
By week 26, albuminuria reductions occurred in all treatment arms, but the extent of reduction was greater in both the dulaglutide arms compared with the insulin glargine arm (percentage UACR**** change from baseline, -27.7 percent and -26.7 percent vs -16.4 percent).
Commenting on the changes in kidney function in terms of eGFR, Tuttle said, “The eGFR declined at 26 weeks at about 2 mL/min/1.73m2 in the insulin-treated group, note that in patients at this stage of CKD we expect about 4-5 mL/min loss, so they were right on target as expected for the insulin group. But this was essentially extinguished in the dulaglutide groups where there was no significant loss in eGFR during the 26-week time period.”
The open-label phase III trial randomized 576 patients (mean age 64.6 years) with T2D and stage 3–4 CKD in a 1:1:1 ratio to dulaglutide 1.5 mg or 0.75 mg once weekly or titrated insulin glargine, in addition to insulin lispro (adjusted to target preprandial plasma glucose value of 6.7–10.0 mmol/L).
Previously, dulaglutide 1.5 mg has demonstrated superiority to daily insulin glargine in terms of HbA1c change from baseline in the AWARD-2 study. The current AWARD-7 enrolled a specific group of T2D patients with moderate-to-severe CKD.
As expected, fewer participants in the dulaglutide arms experienced hypoglycaemia compared with the insulin glargine arm (0 percent and 2.6 percent vs 6.7 percent) at week 26, with significantly lower hypoglycaemia event rate (5.5 and 7.8 vs 17.1 events/participant/year; p<0.001 for both). Also, body weight decreased from baseline with both dulaglutide doses at 26 and 52 weeks but increased with insulin glargine (p<0.001 at both time points).
“Overall there was no significant difference between the insulin and either dose of dulaglutide,” said Tuttle. “The only difference we found was a higher rate of gastrointestinal side effect in the dulaglutide-treated patients, which was expected. There was an increase in a dose-related fashion so that the highest rates of diarrhoea, nausea, and vomiting were observed in the higher-dose dulaglutide group.”