IDegLira is efficacious across baseline HbA1c categories in subjects with Type 2 diabetes uncontrolled on sulphonylurea, glucagon-like peptide-1 receptor agonist or insulin glargine U100: analyses from completed phase 3b trials

Aims: Previous analyses of phase 3a trials (DUAL I extension;DUAL II) showed IDegLira (insulin degludec/liraglutide combina-tion) is efficacious irrespective of baseline HbA1c. This analysisaimed to confirm this observation in additional populations withType 2 diabetes uncontrolled on (i) a glucagon-like peptide-1receptor agonist (GLP-1RA) (DUAL III: IDegLira vs unchangedGLP-1RA), (ii) sulphonylurea metformin (DUAL IV: IDegLiravs placebo) or (iii) insulin glargine (IGlar U100) (DUAL V:IDegLira vs continued IGlar U100 titration). Methods: DUAL III–V were 26 week, randomised trials. IDe-gLira starting dose was 10 dose steps (1 dose step = 1 unit IDeg +0.036mg Lira) in DUAL IV and 16 dose steps in DUAL III and V;maximum IDegLira dose: 50 dose steps. This post hoc analysisgrouped subjects by baseline HbA1c; ≤7.5, > 7.5–≤8.5and > 8.5%.Results: In all trials a higher baseline HbA1c resulted in greaterHbA1c reductions. The change in HbA1c was significantly greater(p 7.5–≤8.5 and > 8.5%: -0.74, -1.13, -1.18; -0.91, -1.00, -1.36; -0.48, -0.55, -0.68 for DUAL III, IV and V,respectively). In all trials for all baseline HbA1c groups, IDegLiradecreased mean HbA1c to 9% (median 9.5%),HbA1c was reduced to 6.9% with IDegLira vs 7.8% with IGlarU100. Conclusions: Significant HbA1c reductions occur with IDegLiraregardless of baseline HbA1c group or study population.Sin financiaciónNo data (2017)UE

Efficacy and safety of once‐monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo‐controlled, 16‐week randomized dose‐finding study

AIMS: To determine the optimal dose(s) of once-monthly administration of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) inadequately controlled on metformin. MATERIALS AND METHODS: In this phase 2, randomized, placebo-controlled, double-blind trial (NCT02081118), patients were randomized 1:1:1:1 to subcutaneous efpeglenatide (8, 12 or 16 mg once monthly; n = 158) or placebo (n = 51). The 16-week treatment period included a 4-week titration phase with once-weekly efpeglenatide 4 mg, followed by one dose of efpeglenatide 8 mg once monthly and two doses of the assigned once-monthly dose. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to week 17. RESULTS: All efpeglenatide doses significantly reduced HbA1c versus placebo (P < 0.0001 for all). Overall, the least squares mean difference in HbA1c reductions between efpeglenatide and placebo was -7.7 mmol/mol (-0.71%; baseline to week 17). At week 17, a significantly greater proportion of efpeglenatide patients had an HbA1c level <53 mmol/mol (<7%) versus placebo (48.7% vs. 30.6%; P = 0.0320). Significant body weight loss occurred across all efpeglenatide doses (placebo-corrected reduction -2.0 kg [efpeglenatide overall]; P = 0.0003). The safety profile was consistent with GLP-1RAs, with gastrointestinal (GI) disorders being the most common treatment-emergent adverse events. Fluctuations in effects on glucose levels and rates of GI events occurred between peak and trough efpeglenatide concentrations. CONCLUSIONS: Efpeglenatide once monthly (following once-weekly titration) has significant benefits with regard to HbA1c and weight reduction versus placebo in patients with T2D. Further studies are needed to evaluate the long-term efficacy and safety of efpeglenatide once monthly