Effect of once weekly dulaglutide by baseline beta‐cell function in people with type 2 diabetes in the AWARD programme

Abstract

Glucagon‐like peptide‐1 receptor agonists lower blood glucose in type 2 diabetes (T2D) partially through glucose‐dependent stimulation of insulin secretion. The aim of this study was to investigate whether beta‐cell function (as measured by HOMA2‐%B) at baseline affects the glycaemic response to dulaglutide. Dulaglutide‐treated patients from AWARD‐1, AWARD‐3 and AWARD‐6 clinical studies were categorised based on their homeostatic model assessment of beta‐cell function (HOMA2‐%B) tertiles. Changes in glycaemic measures in response to treatment with once‐weekly dulaglutide were evaluated in each HOMA2‐%B tertile. Patients with low HOMA2‐%B had higher baseline glycated haemoglobin (HbA1c), fasting and postprandial blood glucose, and longer duration of diabetes (P < .001, all) (mean low, middle and high tertiles with dulaglutide 1.5 mg: HOMAB‐2%B, 31%, 58%, 109%; HbA1c, 8.7%, 7.7%, 7.3%, respectively). At 26 weeks, the low tertile experienced larger reductions in HbA1c compared to the high tertile with dulaglutide 1.5 mg (mean; −1.55% vs. −0.98% [−16.94 vs. −10.71 mmol/mol]). Differences between low and high tertiles disappeared when adjusted for baseline HbA1c (LSM; −1.00 vs. −1.18% [−10.93 vs. −12.90 mmol/mol]). Greater decreases in fasting blood glucose and greater increases in fasting C‐peptide were observed in the low tertile. Similar increases in HOMA2‐%B were observed in all tertiles. Dulaglutide demonstrated clinically relevant HbA1c reduction irrespective of estimated baseline beta‐cell function.

Association of glucagon‐like peptide‐1 receptor‐targeted imaging probe with in vivo glucagon‐like peptide‐1 receptor agonist glucose‐lowering effects

“…Accumulating clinical data has suggested that reduced glucose-lowering effects of some GLP-1RAs could be partly due to reduced insulin secretory capacity [2][3][4][5][6][7] . Several indices related to insulin secretory capacity have been described as valuable parameters to avoid termination of GLP-1RAs in the case of hyperglycemia [2][3][4] .…”

“…As clinical predictors of the GLP-1RA response, some previous reports have suggested shorter diabetes duration, lower total insulin dose and preserved b-cell function, as determined by the increment of serum C-peptide during glucagon stimulation test, post-meal serum C-peptide index and the increment of serum C-peptide 120 min after 75-g oral glucose load [2][3][4][5][6] . However, the cut-off values vary, and the reliability of b-cell function calculations as a predictor for efficacy of GLP-1RA has not been fully established 7 . Furthermore, it remains challenging to exclude non-responders to GLP-1RA, as reduced b-cell function is often difficult to establish in clinical settings because of apparently reduced insulin secretory capacity in chronic hyperglycemia and glucose toxicity 2,3 .…”

Impact of patient characteristics on efficacy and safety of once-weekly semaglutide versus dulaglutide: SUSTAIN 7 post hoc analyses

“…21 22 Post hoc analyses of the SUSTAIN and the AWARD trials have analysed patient subgroups across the continuum of T2D care. [23][24][25][26][27][28][29][30][31][32][33][34][35] Such analyses showed consistent, clinically relevant reductions in glycated haemoglobin (HbA 1c ) and body weight (BW) with semaglutide across patient subgroups based on characteristics including age, baseline body mass index (BMI), baseline HbA 1c , diabetes duration, race and ethnicity. 23-26 28 Dulaglutide has also been shown to be efficacious across subgroups based on sex, age, duration of diabetes, beta-cell function, HbA 1c , BW and BMI.…”

“…23-26 28 Dulaglutide has also been shown to be efficacious across subgroups based on sex, age, duration of diabetes, beta-cell function, HbA 1c , BW and BMI. [29][30][31][32][33][34][35] In the phase 3b SUSTAIN 7 clinical trial, semaglutide and dulaglutide were compared head-to-head in subjects with T2D on background treatment with metformin. 36 The trial showed superior reductions in HbA 1c and BW with semaglutide versus dulaglutide, for both low-dose (semaglutide 0.5 mg vs dulaglutide 0.75 mg) and highdose (semaglutide 1.0 mg vs dulaglutide 1.5 mg) comparisons.…”

Efficacy and Safety of Dulaglutide Monotherapy Compared to Glimepiride in Oral Antihyperglycemic Medication-Naïve Chinese patients with Type 2 Diabetes: A Post Hoc Analysis of AWARD-CHN1

“…The duration of the study was relatively short considering the chronic nature of T2D, hence these HOMA2-%B results should be interpreted prudently. In the long run, the rise in HOMA2-%B may not translate into long-term improvement in beta cell function, and in fact may reflect a GLP-1 receptor agonist-mediated increase in insulin secretion [30].…”