Association among weight change, glycemic control, and markers of cardiovascular risk with exenatide once weekly: a pooled analysis of patients with type 2 diabetes.
Level 2 - randomized trial
Pooled post-hoc analysis of data from eight randomized controlled trials
PubMed 25645567 · doi:10.1186/s12933-014-0171-2
What was done
Researchers conducted a pooled analysis of eight clinical trials evaluating exenatide once weekly in patients with type 2 diabetes mellitus. Participants were categorized into quartiles based on their degree of weight change: Quartile 1 (greatest weight loss) through Quartile 4 (least loss or weight gain). Changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), blood pressure, heart rate, lipid profiles (HDL-C, LDL-C, total cholesterol, triglycerides), and liver transaminases (ALT, AST) were evaluated across quartiles.
What was found
Median changes in body weight across Quartiles 1 through 4 were -6.0 kg, -3.0 kg, -1.0 kg, and +1.0 kg, respectively. All quartiles experienced reductions in A1C (-1.6%, -1.4%, -1.1%, and -1.2%) and FPG (-41, -40, -31, and -25 mg/dL), with the largest reductions occurring in Quartiles 1 and 2. Most cardiovascular risk markers (excluding diastolic blood pressure) and liver enzymes improved in Quartiles 1 to 3 but remained relatively unchanged in Quartile 4. Quartile 1 showed higher rates of gastrointestinal adverse events and hypoglycemia compared to Quartiles 2 through 4.
Why it matters
This study demonstrates that the glycemic efficacy of exenatide once weekly occurs partly independent of weight change, though concurrent weight loss confers additional cardiovascular and metabolic risk factor improvements.
Limits
The total sample size, trial durations, and background diabetes therapies were not reported in the abstract. Stratification by post-baseline weight change disrupts randomized treatment comparisons, introducing potential confounding from differences in adherence, diet, or baseline characteristics between quartiles.
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