Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial

Tuttle, Katherine R.; Lakshmanan, Mark; Rayner, Brian; Busch, Robert S.; Zimmermann, Alan G.; Woodward, D. Bradley; Botros, Fady T.

doi:10.1016/s2213-8587(18)30104-9

Cited by 479 publications

(479 citation statements)

References 26 publications

Supporting

Mentioning

448

Contrasting

Unclassified

Order By: Relevance

“…7 All statistical analyses were implemented using SAS version 9.1 or higher. Other data analyses were described previously.…”

Section: Discussionmentioning

confidence: 99%

“…7 Creatinine clearance (CrCL) was also evaluated using the Cockcroft-Gault equation based on total BW or estimated baseline lean BW. Participants were randomized (1:1:1) to receive weekly dulaglutide 1.5 mg or dulaglutide 0.75 mg or daily glargine.…”

Section: Research Design and Participantsmentioning

confidence: 99%

“…2,3 Furthermore, evaluation of the effects of anti-hyperglycaemic agents on kidney function is crucial for patient safety. 7 In the AWARD-7 study, eGFR was evaluated with both creatinine and cystatin C. The *Retired. In daily practice, the estimated GFR (eGFR) is typically based on serum creatinine, but is subject to certain provisos.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Body weight and eGFR during dulaglutide treatment in type 2 diabetes and moderate‐to‐severe chronic kidney disease (AWARD‐7)

Lakshmanan

Rayner

Zimmermann

et al. 2019

Diabetes Obesity Metabolism

Self Cite

View full text Add to dashboard Cite

In patients with type 2 dibetes and moderate-to-severe chronic kidney disease, dulaglutide treatment led to body weight (BW) loss and lesser eGFR decline compared to insulin glargine.As BW may affect muscle mass, creatinine-based eGFR can be altered independently of kidney function. Cystatin C-based eGFR is not affected by muscle mass. The objective of this post-hoc analysis was to determine whether the lesser eGFR decline with dulaglutide was related to BW loss. Baseline characteristics were similar between treatments ([mean ± SD] age, 64.6 ± 8.6 years; women, 48%; BW, 89.1 ± 17.7 kg; eGFR [CKD-EPI-cystatin C] 38 ± 14 mL/min/1.73m 2 ). BW decreased with dulaglutide 1.5 and 0.75 mg and increased with insulin glargine ([LSM change (SE)], −2.66 [0.47] kg and −1.71 [0.45] vs 1.57 [0.43] kg; P < 0.001). Changes in eGFR were not significant with dulaglutide 1.5 and 0.75 mg, but eGFR significantly decreased with insulin glargine (eGFR-CKD-EPI-cystatin C [LSM change (95%CI)], −0.7 [−2.5, 1.0] and −0.7 [−2.4, 1.1] vs −3.3 [−5.1, −1.6] mL/min/1.73 m 2 ; P ≤ 0.037 vs glargine). Changes in BW did not correlate with changes in eGFR-CKD-EPI-cystatin C (r = −0.041; n = 471; P = 0.379) or eGFR-CKD-EPIcreatinine (r = −0.074; n = 473; P = 0.106). In conclusion, the lesser decline in eGFR observed with dulaglutide was not influenced by BW loss. K E Y W O R D S GLP-1, type 2 diabetes | INTRODUCTIONThe leading cause of chronic kidney disease (CKD) worldwide is diabetes. 1,2 Patients with moderate-to-severe CKD (eGFR of <60 to ≥15 mL/min/1.73m 2 ) and type 2 diabetes (T2D) have limited treatment options for hyperglycaemia. 2,3 Furthermore, evaluation of the effects of anti-hyperglycaemic agents on kidney function is crucial for patient safety. 2,4 Direct measurement of the glomerular filtration rate (GFR) by administration of exogenous clearance markers is laborious and not widely available in clinical settings. In daily practice, the estimated GFR (eGFR) is typically based on serum creatinine, but is subject to certain provisos. The serum creatinine level must be in steady-state when rates of production from muscle and elimination by the kidney are equilibrated. As production of serum creatinine is highly dependent on muscle mass, changes in body weight (BW) driven by alterations in muscle mass affect serum creatinine levels. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause BW loss, raising the concern that serum creatinine may not accurately reflect eGFR if there are associated changes in muscle mass. As cystatin C is a marker for eGFR that is not dependent on muscle, it may provide a more accurate eGFR in this context. 5Dulaglutide is a once-weekly GLP-1 RA that demonstrates glycaemic efficacy and BW loss. 6 In the AWARD-7 study, dulaglutide treatment was associated with smaller decline in eGFR and reduction in BW compared to insulin glargine (glargine) treatment in participants with T2D and moderate-to-severe CKD. 7 In the AWARD-7 study, eGFR was evaluated with both creatinine and cystatin C. The

show abstract

“…7 All statistical analyses were implemented using SAS version 9.1 or higher. Other data analyses were described previously.…”

Section: Discussionmentioning

confidence: 99%

Section: Research Design and Participantsmentioning

confidence: 99%

See 1 more Smart Citation

Body weight and eGFR during dulaglutide treatment in type 2 diabetes and moderate‐to‐severe chronic kidney disease (AWARD‐7)

Lakshmanan

Rayner

Zimmermann

et al. 2019

Diabetes Obesity Metabolism

Self Cite

View full text Add to dashboard Cite

show abstract

“…25 Among the reported 13 studies, AWARD-4 and AWARD-7 26 were the only studies evaluating the combination of a GLP-1 RA with up-titrated prandial insulin. However, results from the AWARD-4 study are in line with results from the combination of GLP-1 RAs with insulin that was evaluated in a recent meta-analysis in comparison to a basal-bolus or basal-plus regimen (mean body weight difference, −3.72 kg).…”

Section: Discussionmentioning

confidence: 99%

Weight loss in patients with type 2 diabetes receiving once‐weekly dulaglutide plus insulin lispro or insulin glargine plus insulin lispro: A post‐hoc analysis of the AWARD‐4 study across baseline body mass index subgroups

Fuechtenbusch¹,

Aberle

Heitmann

et al. 2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Aims: Insulin-treated patients with type 2 diabetes (T2D) and obesity are challenged in achieving body weight stability or reduction, in addition to glycaemic control. Post-hoc analyses of body weight and insulin dose data from the AWARD-4 trial involved comparison of treatment with once-weekly dulaglutide 1.5 mg (N = 295) or 0.75 mg (N = 293) and treatment with daily insulin glargine (N = 296), each with prandial insulin lispro (± metformin).Materials and methods: Changes in weight and in the proportion of patients without weight gain or with weight loss of at least 3%, 5% or 10% or composites of HbA1c less than 7% without weight gain and weight loss of at least 3% after 52 weeks were compared between the dulaglutide (either dose) groups and the insulin glargine group, overall and by baseline BMI (<30, 30-<35, ≥35 kg/m 2 ), using analysis of covariance and logistic regression, including interaction terms. Results:The following parameters were statistically significant (P < 0.01) in favour of the dulaglutide-treated groups, at lower mean total daily insulin doses, vs the insulin glargine group.The achieved targets were more pronounced with dulaglutide 1.5 mg than with insulin glargine: LSM weight change difference, −3.23 kg; proportion of patients without weight gain, 49.0% vs 19.0%; proportion of patients with weight loss ≥3%, 21.7% vs 5.7% or with weight loss ≥5%, 10.5% vs 2.4%; proportion of patients with HbA1c <7% without weight gain, 26.2% vs 7.9%;proportion of patients with HbA1c <7% and weight loss ≥3%, 11.9% vs 1.4%, respectively. Treatment effect for these parameters was not significantly different across BMI categories.Conclusions: Larger proportions of patients in late-stage T2D needing treatment intensification achieved glycemic control without weight gain or with weight loss at lower insulin doses with once-weekly dulaglutide plus daily prandial insulin than with a basal-bolus insulin regimen, overall and across all three BMI subgroups.

show abstract

“…Dulaglutide was also associated with a reduced decline in eGFR (a secondary outcome of the trial) compared with insulin glargine . After 52 weeks, eGFR was higher with dulaglutide 1.5 mg (34.0 mL/min/1.73 m 2 ; P = .005 vs insulin glargine) and dulaglutide 0.75 mg (33.8 mL/min/1.73 m 2 ; P = .009 vs insulin glargine) compared with insulin glargine (31.3 mL/min/1.73 m 2 ).…”

Section: Renal Effects Of Glp‐1rasmentioning

confidence: 96%

Review of glucagon‐like peptide‐1 receptor agonists for the treatment of type 2 diabetes mellitus in patients with chronic kidney disease and their renal effects

Sloan

2019

Journal of Diabetes

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is the most common cause of chronic kidney disease (CKD), and when it causes CKD it is collectively referred to as diabetic kidney disease. One of the newer therapies for managing hyperglycemia is the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) drug class. This review summarizes the effects of GLP‐1RAs in patients with T2DM with CKD and evidence for renoprotection with GLP‐1RAs using data from observational studies, prospective clinical trials, post hoc analyses, and meta‐analyses. Evidence from some preclinical studies was also reviewed. Taken together, subgroup analyses of patients with varying degrees of renal function demonstrated that glycemic control with GLP‐1RAs was not markedly less effective in patients with mild or moderate renal impairment vs that in patients with normal function. GLP‐1RAs were associated with improvements in some cardiorenal risk factors, including systolic blood pressure and body weight. Furthermore, several large cardiovascular outcome studies showed reduced risks of composite renal outcomes, mostly driven by a reduction in macroalbuminuria, suggesting potential renoprotective effects of GLP‐1RAs. In conclusion, GLP‐1RAs effectively reduced hyperglycemia in patients with mild or moderately impaired kidney function in the limited number of studies to date. GLP‐1RAs may be considered in combination with other glucose‐lowering medications because of their ability to lower glucose in a glucose‐dependent manner, lowering their risk for hypoglycemia, while improving some cardiorenal risk factors. Potential renoprotective effects of GLP‐1RAs, and their renal mechanisms of action, warrant further investigation.

show abstract

Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial

Cited by 479 publications

References 26 publications

Body weight and eGFR during dulaglutide treatment in type 2 diabetes and moderate‐to‐severe chronic kidney disease (AWARD‐7)

Body weight and eGFR during dulaglutide treatment in type 2 diabetes and moderate‐to‐severe chronic kidney disease (AWARD‐7)

Weight loss in patients with type 2 diabetes receiving once‐weekly dulaglutide plus insulin lispro or insulin glargine plus insulin lispro: A post‐hoc analysis of the AWARD‐4 study across baseline body mass index subgroups

Review of glucagon‐like peptide‐1 receptor agonists for the treatment of type 2 diabetes mellitus in patients with chronic kidney disease and their renal effects

Contact Info

Product

Resources

About