Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)

OBJECTIVE: In patients with type 2 diabetes uncontrolled with metformin, exenatide once weekly (QW) plus dapagliflozin produced greater reductions in glycemic parameters (glycated haemoglobin [HbA1c], fasting plasma glucose [FPG], and 2-hour postprandial glucose [2-h PPG]), weight, and systolic blood pressure (SBP) than exenatide QW or dapagliflozin alone after 28 weeks of treatment in DURATION-8. Following a 24‑week extension period, improvements were sustained at 52 weeks. Here, we investigated efficacy and safety at 104 weeks after randomization. RESEARCH DESIGN AND METHODS: DURATION-8 was a 104-week, multicenter, double-blind, randomized, active‑controlled, phase 3 trial. In total, 695 adults (age ≥18 years) with type 2 diabetes and inadequate glycemic control (HbA1c, 8.0%–12.0% [64–108 mmol/mol]) despite stable metformin monotherapy (≥1500 mg/day) were randomly assigned (1:1:1) to receive exenatide 2 mg QW plus once-daily dapagliflozin 10 mg, exenatide QW plus placebo, or dapagliflozin plus placebo. All 104-week evaluations were exploratory. RESULTS: At week 104, 431 (62.0%) patients completed treatment. The adjusted least squares mean (LSM) change [standard error] from baseline to week 104 in HbA1c was greater with exenatide QW plus dapagliflozin (–1.70% [0.11]) versus exenatide QW plus placebo (–1.29% [0.12]; P=0.007) and dapagliflozin plus placebo (–1.06% [0.12]; P<0.001). Clinically relevant changes in FPG, 2-h PPG, weight and SBP were also observed with exenatide QW plus dapagliflozin. There were no unexpected safety findings and exenatide QW plus dapagliflozin was well tolerated, with no episodes of major hypoglycemia. CONCLUSIONS: In this exploratory analysis, among those individuals who completed the trial without rescue therapy, there was clinically relevant efficacy over 2 years with exenatide QW plus dapagliflozin, with no unexpected safety findings.

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Efficacy and safety over 2 years of exenatide plus dapagliflozin in the DURATION-8 study: a multicenter, double-blind, phase 3, randomized controlled trial

10.2337/figshare.12692078 ◽

2020 ◽

Author(s):

Serge A Jabbour ◽

Juan P Frías ◽

Azazuddin Ahmed ◽

Elise Hardy ◽

Jasmine Choi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Rescue Therapy ◽

Controlled Trial ◽

Glycated Haemoglobin ◽

Efficacy And Safety ◽

Phase 3 ◽

Double Blind ◽

Exenatide Qw ◽

Adjusted Least Squares

OBJECTIVE: In patients with type 2 diabetes uncontrolled with metformin, exenatide once weekly (QW) plus dapagliflozin produced greater reductions in glycemic parameters (glycated haemoglobin [HbA1c], fasting plasma glucose [FPG], and 2-hour postprandial glucose [2-h PPG]), weight, and systolic blood pressure (SBP) than exenatide QW or dapagliflozin alone after 28 weeks of treatment in DURATION-8. Following a 24‑week extension period, improvements were sustained at 52 weeks. Here, we investigated efficacy and safety at 104 weeks after randomization. RESEARCH DESIGN AND METHODS: DURATION-8 was a 104-week, multicenter, double-blind, randomized, active‑controlled, phase 3 trial. In total, 695 adults (age ≥18 years) with type 2 diabetes and inadequate glycemic control (HbA1c, 8.0%–12.0% [64–108 mmol/mol]) despite stable metformin monotherapy (≥1500 mg/day) were randomly assigned (1:1:1) to receive exenatide 2 mg QW plus once-daily dapagliflozin 10 mg, exenatide QW plus placebo, or dapagliflozin plus placebo. All 104-week evaluations were exploratory. RESULTS: At week 104, 431 (62.0%) patients completed treatment. The adjusted least squares mean (LSM) change [standard error] from baseline to week 104 in HbA1c was greater with exenatide QW plus dapagliflozin (–1.70% [0.11]) versus exenatide QW plus placebo (–1.29% [0.12]; P=0.007) and dapagliflozin plus placebo (–1.06% [0.12]; P<0.001). Clinically relevant changes in FPG, 2-h PPG, weight and SBP were also observed with exenatide QW plus dapagliflozin. There were no unexpected safety findings and exenatide QW plus dapagliflozin was well tolerated, with no episodes of major hypoglycemia. CONCLUSIONS: In this exploratory analysis, among those individuals who completed the trial without rescue therapy, there was clinically relevant efficacy over 2 years with exenatide QW plus dapagliflozin, with no unexpected safety findings.

Download Full-text