Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly alone, or dapagliflozin alone added to metformin monotherapy in subgroups of patients with type 2 diabetes in the DURATION‐8 randomized controlled trial

Abstract

This analysis assessed whether responses with exenatide once weekly plus dapagliflozin (n = 231), exenatide once weekly alone (n = 230), or dapagliflozin alone (n = 233) differed in key patient subpopulations of the DURATION‐8 trial. Potential treatment‐by‐subgroup interactions for changes in glycated haemoglobin (HbA1c) and body weight after 28 weeks were evaluated among subgroups determined by baseline HbA1c, age, sex, body mass index, type 2 diabetes duration, race, ethnicity and estimated glomerular filtration rate (eGFR). Exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all subgroups: least‐squares mean reductions ranged from −8.4 to −26.1 mmol/mol (−0.77% to −2.39%) for HbA1c and from −2.07 to −4.55 kg for body weight. Potential treatment‐by‐subgroup interactions (P < .10) were found for HbA1c change by age (P = .016) and eGFR (P = .097). Age subgroup analysis findings were not consistent with expected mechanistic effects, with the small number of patients aged ≥65 years (n = 74 vs n = 499 for patients aged <65 years) limiting the interpretability of the interaction term. In the exenatide once weekly plus dapagliflozin and dapagliflozin groups, but not the exenatide once weekly group, HbA1c reductions were greater among patients with eGFR ≥90 vs ≥60 to <90 mL/min/1.73 m2 (least‐squares mean reductions of −23.6 vs −19.0 mmol/mol [−2.16% vs −1.74%], −17.3 vs −12.0 mmol/mol [−1.58% vs −1.10%], and −17.7 vs −16.9 mmol/mol [−1.62% vs −1.55%] for the respective treatments); this was consistent with the mechanism of action of dapagliflozin. A potential treatment‐by‐subgroup interaction was observed for change in body weight by sex (P = .099), with greater weight loss for women vs men across all treatments (range −2.56 to −3.98 kg vs −0.56 to −2.99 kg). In conclusion, treatment with exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all patient subgroups and was more effective than exenatide once weekly or dapagliflozin alone in all adequately sized subgroups.

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

“…Furthermore, a converse relationship between weight loss and baseline HbA 1c levels was observed, whereby increasing baseline HbA 1c was associated with greater reductions in HbA 1c but a decreasing magnitude of weight loss. A similar pattern has been observed with liraglutide as an add-on to insulin treatment, 41 with exenatide alone 42 and with dulaglutide. 31 32 These findings have relevance for clinical practice, indicating that there may be an effect with GLP-1RAs (and potentially other antihyperglycaemic therapies) in predicting treatment responses based on HbA 1c levels.…”

Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors as combination therapy for type 2 diabetes: A systematic review and meta‐analysis

“…Seven RCTs with 1913 patients were included in the systematic review and meta-analysis ( Figure 1). [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Of these, two studies were retrieved as conference abstracts and one study was identified in ClinicalTrials.gov (NCT02964247). 25,28 Of note, for one of these conference abstracts and for the trial from ClinicalTrials.gov, we utilized post hoc data from their respective journal articles, which were published shortly after our search date.…”

Similar effectiveness of dapagliflozin and GLP‐1 receptor agonists concerning combined endpoints in routine clinical practice: A multicentre retrospective study

“…A head-tohead comparative randomized controlled trial (RCT) showed superiority of exenatide once weekly (EOW) vs dapagliflozin when added to metformin monotherapy, 9 especially in patients with CKD. 10 However, a network meta-analysis comparing GLM, added after dualtherapy failure, suggested no significant difference in the glycaemic effects of GLP-1RAs and SGLT2is. 11 In addition to lowering HbA1c, both GLP-1RAs and SGLT2is significantly improve body weight (BW) and blood pressure (SBP).…”

“…Overall, GLP‐1RAs are supposed to be more effective in lowering glucose than are SGLT2is. A head‐to‐head comparative randomized controlled trial (RCT) showed superiority of exenatide once weekly (EOW) vs dapagliflozin when added to metformin monotherapy, especially in patients with CKD . However, a network meta‐analysis comparing GLM, added after dual‐therapy failure, suggested no significant difference in the glycaemic effects of GLP‐1RAs and SGLT2is .…”