Many antihyperglycaemic drugs, including insulin, are primarily cleared by the kidneys, restricting treatment options for patients with kidney disease. Dulaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist that is not cleared by the kidneys, and confers a lower risk of hypoglycaemia than insulin. The AWARD-7 trial has shown that in patients with type 2 diabetes (T2D) and moderate-to-severe chronic kidney disease, once-weekly dulaglutide produced glycaemic control similar to that achieved with insulin glargine, with reduced decline in estimated glomerular filtration rate (eGFR) and significant weight loss.

• This post-hoc analysis of AWARD-7 assessed if the smaller decline in eGFR observed with dulaglutide is related to body weight loss.

Type of study, patients, and inclusion criteria

• AWARD-7 was a multicentre, open-label trial performed at 99 sites in nine countries.
• Participants were randomly assigned (1:1:1) to once-weekly injectable dulaglutide 1.5 mg, once-weekly dulaglutide 0.75 mg, or daily insulin glargine as basal therapy, all in combination with insulin lispro, for 52 weeks.
• Eligible patients were adults with T2D and moderate-to-severe chronic kidney disease (stages 3-4), with an HbA_1c of 7.5-10.5%, and who were being treated with insulin or insulin plus an oral antihyperglycaemic drug and taking a maximum tolerated dose of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.

Patient population

• Total number of enrolees: 577.
• Duration of follow-up: 52 weeks.

Primary outcome measure

• HbA_1c at 26 weeks, with a 0.4% non-inferiority margin.

Secondary outcome measures

• eGFR and urine albumin-to-creatinine ratio (UACR).

Main findings of AWARD-7

• Treatment with dulaglutide is associated with body weight loss and smaller decline in eGFR compared to insulin glargine (Figure).

Main findings of the post-hoc analysis

• There was no significant correlation between change in serum creatinine and change in body weight.
• There was no significant correlation between change in serum cystatin-C (a biomarker of kidney function which is not impacted by muscle mass) and change in body weight.
• There was no significant correlation between change in eGFR (CKD-EPI-cystatin C) and change in body weight.

• Treatment with dulaglutide is associated with body weight loss and smaller decline in eGFR compared to insulin glargine.
• In people with T2D and moderate to severe chronic kidney disease, dulaglutide was consistently associated with smaller eGFR decline compared to insulin glargine when serum creatinine or cystatin C were used to estimate eGFR.
• Changes in eGFR were independent of body weight changes; body weight loss or gain was not associated with greater changes in serum creatinine, cystatin C, or eGFR.