Association among weight change, glycemic control, and markers of cardiovascular risk with exenatide once weekly: a pooled analysis of patients with type 2 diabetes - PubMed (original) (raw)
Randomized Controlled Trial
Association among weight change, glycemic control, and markers of cardiovascular risk with exenatide once weekly: a pooled analysis of patients with type 2 diabetes
Lawrence Blonde et al. Cardiovasc Diabetol. 2015.
Abstract
Background: Overweight or obesity contributes to the development of type 2 diabetes mellitus (T2DM) and increases cardiovascular risk. Exenatide, a glucagon-like peptide-1 receptor agonist, significantly reduces glycated hemoglobin (A1C) and body weight and improves cardiovascular risk markers in patients with T2DM. As weight loss alone has been shown to reduce A1C and cardiovascular risk markers, this analysis explored whether weight loss contributed importantly to clinical responses to exenatide once weekly.
Methods: A pooled analysis from eight studies of exenatide once weekly was conducted. Patients were distributed into quartiles from greatest weight loss (Quartile 1) to least loss or gain (Quartile 4). Parameters evaluated for each quartile included A1C, fasting plasma glucose (FPG), blood pressure (BP), heart rate, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Results: The median changes from baseline in body weight in Quartiles 1-4 were -6.0, -3.0, -1.0, and +1.0 kg, respectively. All quartiles had reductions in A1C (median changes -1.6, -1.4, -1.1, and -1.2%, respectively) and FPG (-41, -40, -31, and -25 mg/dL, respectively), with the greatest decreases in Quartiles 1 and 2. Most cardiovascular risk markers (except diastolic BP) and liver enzymes improved in Quartiles 1 through 3 and were relatively unchanged in Quartile 4. Higher rates of gastrointestinal adverse events and hypoglycemia were observed in Quartile 1 compared with Quartiles 2 through 4.
Conclusions: Exenatide once weekly improved glycemic parameters independent of weight change, although the magnitude of improvement increased with increasing weight loss. The greatest trend of improvement in glycemic parameters, cardiovascular risk factors including systolic BP, LDL-C, total cholesterol, and triglycerides, and in liver enzymes, was seen in the patient quartiles with the greatest reductions in body weight.
Figures
Figure 1
Distribution of median change in body weight, by end-point body weight change quartiles. The central line represents the median (also labelled above the plot), the box encloses the 25th to 75th percentiles of the distribution, and the outer bars are drawn to the 10th and 90th percentiles.
Figure 2
Median changes in A1C and FPG, by end-point body weight change quartiles. (A) A1C. (B) FPG. A1C, hemoglobin A1C; FPG, fasting plasma glucose. The central line represents the median (also labelled above the plot), the box encloses the 25th to 75th percentiles of the distribution, and the outer bars are drawn to the 10th and 90th percentiles.
Figure 3
Pearson linear correlation of change in body weight and change in A1C. The solid black line represents the regression. Dotted lines represent the maximum body weight change in Quartiles 1 through 3. The r-value for all patients was 0.1579, and r-values for Quartiles 1 through 4 were 0.1847, 0.0267, 0.0485, and −0.0542, respectively. A1C, hemoglobin A1C; Q, quartile.
Figure 4
Median changes in blood pressure and lipids, by end-point body weight change quartiles. (A) SBP. (B) DBP. (C) HDL-C. (D) LDL-C. (E) Total cholesterol. (F) Triglycerides. DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure. The central line represents the median (also labelled above the plot), the box encloses the 25th to 75th percentiles of the distribution, and the outer bars are drawn to the 10th and 90th percentiles.
Figure 5
Median changes in ALT and AST, by end-point body weight change quartiles. (A) ALT. (B) AST. ALT, alanine aminotransferase; AST, aspartate aminotransferase. The central line represents the median (also labelled above the plot), the box encloses the 25th to 75th percentiles of the distribution, and the outer bars are drawn to the 10th and 90th percentiles.
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