Variability in and predictors of glycaemic responses after 24 weeks of treatment with exenatide twice daily and exenatide once weekly

Abstract

The range of glycated haemoglobin (HbA1c) responses and characteristics associated with above‐average response to exenatide twice daily and once weekly were examined. Data were pooled from 8 exenatide‐twice‐daily and 5 exenatide‐once‐weekly studies. A baseline HbA1c‐corrected measure of change in HbA1c after 24 weeks identified high, average and low responses. Multiple linear regression and multivariate generalized estimating equation models identified factors associated with high response. Among 2355 participants (exenatide twice daily, n = 1414; exenatide once weekly, n = 941), baseline HbA1c correlated with change in HbA1c (P < .0001). Across baseline HbA1c levels, the 25th to 75th percentile of HbA1c change ranged from −0.3% to −3.2% with exenatide twice daily and from −0.5% to −3.6% with exenatide once weekly. Asian ethnicity and older age were significantly associated with high response to exenatide twice daily; no factors were significantly associated with response to exenatide once weekly. These data provide clinically useful information for estimating the likelihood that, depending on baseline HbA1c, an individual can achieve HbA1c goals. The association between Asian ethnicity, age and high response to exenatide twice daily may relate to the specific effects of exenatide twice daily on postprandial glucose.

Effect of race on cardiometabolic responses to once-weekly exenatide: insights from the Exenatide Study of Cardiovascular Event Lowering (EXSCEL)

“…This distinction was not considered in the meta-analysis, which suggested more potent blood glucose lowering with exenatide in Asians versus non-Asians with type 2 diabetes [6]. However, subsequent analyses of pooled patient-level exenatide data from phase 3 studies have indicated that this benefit is seen with twice-daily but not once-weekly administration [7][8][9][10], consistent with the present EXSCEL Phase IV data.…”

“…A systematic review and meta-analysis found that, although there is no evidence of race-specific differences in the pharmacokinetic properties of GLP-1 RAs, the hemoglobin A 1c (HbA 1c ) reduction in Asian-dominant studies (those with ≥ 50% Asian participants) was 0.32% (3 mmol/mol) greater than in non-Asian-dominant studies [6]. Subsequent analyses of pooled individual patient data from phase 3 studies have suggested that twice-daily exenatide has greater glycemic efficacy in Asians with type 2 diabetes than other races [7][8][9], but that there is no such racial difference in the case of once-weekly exenatide (EQW) [8][9][10]. Race-specific responses of other CVD risk factors, including blood pressure and serum lipids, to exenatide therapy were also assessed in three of these studies, but no formal statistical comparisons were performed [7,9,10].…”

Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors: a systematic review

“… GLP1-RA SGLT2i Plain language summary Glycaemic outcomes GRADE EVIDENCE C GRADE EVIDENCE B Biomarker N (observational) N (RCT) N (Meta-analysis and pooled RCT) N (observational) N (RCT) N (Meta-analysis and pooled RCT) Glycaemia Biomarkers 18 37 – 41 , 45 , 47 , 48 , 54 , 55 , 61 , 62 , 140 – 145 11 32 , 44 , 46 , 50 , 56 , 59 , 63 , 146 – 149 1 53 4 24 , 150 – 152 2 27 , 32 3 15 , 25 , 26 Greater glycaemic response for both SGLT2i and GLP1-RA is seen in individuals with higher baseline HbA1c, No studies are available to comparing the relative efficacy of SGLT2i to GLP1-RA at different baseline HbA1c levels. Renal Function 6 39 , 40 , 45 , 54 , 62 , 142 4 32 , 44 ...…”

Precision medicine in type 2 diabetes: A systematic review of treatment effect heterogeneity for GLP1-receptor agonists and SGLT2-inhibitors

“…Overall, there was no consistent evidence for effect modification by body mass index (BMI), sex, age or kidney function, with studies reporting contrasting, or null, associations for these clinical features 36,37,[41][42][43]47,[51][52][53][54][55][56][57][58][59][60][61] . In comparative analysis, one large observational study found that markers of insulin resistance (including higher HOMA-IR, BMI, fasting triglycerides, and HDL) do not alter GLP1-RA response, but are associated with lesser DPP4-inhibitor response 54 .…”