Dulaglutide as add-on therapy to SGLT-2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised , double-blind, placebo-controlled trial

BACKGROUND: The safety and efficacy of the once-weekly GLP-1 receptor agonist dulaglutide, added to an ongoing treatment regimen in patients inadequately controlled with SGLT2 inhibitors, with or without metformin was investigated. METHODS: This was a phase 3b, double-blind, placebo-controlled, 24-week study. Patients (≥18yrs), HbA1c ≥7.0% [53mmol/mol] and ≤9.5% [80mmol/mol]), BMI ≤45 kg/m2, stable doses of an SGLT2 inhibitor (±metformin) were randomly assigned (1:1:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, or placebo. Patients and investigators were masked to treatment assignment (those assessing outcomes to study drug assignment). The primary objective was to test for the superiority of dulaglutide (1.5 mg or 0.75 mg) vs placebo for change in HbA1c from baseline to 24 weeks. RESULTS: 423 patients were randomly assigned to dulaglutide 1.5 mg (n=142), dulaglutide 0.75 mg (n=141), and placebo (n=140). Greater reduction in HbA1c at 24 weeks was seen in patients receiving dulaglutide (1.5 mg -1.34% [SE 0.06]/14.7 mmol/mol [0.6]; 0.75 mg -1.21% [0.06]/-13.2 mmol/mol [0.6]) than in patients receiving placebo (-0.54% [0.06]/-5.9 mmol/mol [0.6]; p<0.0001 for both groups vs placebo). Serious adverse events were reported for five patients in the dulaglutide 1.5 mg group, three in the dulaglutide 0.75 mg group, and five in the placebo group. Treatment-emergent adverse events were more common in patients treated with dulaglutide: nausea (21 [15%] patients in the dulaglutide 1.5 mg group vs seven [5%] in the dulaglutide 0.75 mg group vs five [4%] in the placebo group), diarrhoea (eight [6%] vs 14 [10%] vs four [3%]), and vomiting (five [4%] vs four [3%] vs one [1%]). One episode of severe hypoglycaemia was reported in the dulaglutide 0.75 mg group. CONCLUSIONS: Dulaglutide as add-on treatment to SGLT2 inhibitors (±metformin) resulted in significant and clinically relevant improvements in glycaemic control, with acceptable tolerability consistent with the established safety profile of dulaglutide