Weight loss, glycemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database

Abstract

Objective: Weight loss in patients with type 2 diabetes can improve glycemic control, lower blood pressure, and improve dyslipidemia. Glucagon-like peptide (GLP-1) receptor agonists are associated with weight loss and have potentially beneficial effects on cardiovascular risk biomarkers; however, there is limited information to indicate whether these effects remain outside of clinical trials.

Research design and methods: Medical records from the General Electric Centricity research database were analyzed retrospectively to evaluate the relationship between weight loss and glycemic control and changes in blood pressure and lipids in patients with type 2 diabetes initiating therapy with exenatide, sitagliptin, or insulin. Baseline and follow-up (90-365 days after the index date) for weight, A1C, fasting blood glucose (FBG), blood pressure, triglycerides, and LDL, HDL, and total cholesterol were assessed.

Results: A total of 6,280, 5,861, and 32,398 patients receiving exenatide, sitagliptin, or insulin, respectively, were included in the analysis. Exenatide-treated patients lost a mean +/- SD of 3.0 +/- 7.33 kg, sitagliptin-treated patients lost 1.1 +/- 5.39 kg, and insulin-treated patients gained 0.6 +/- 9.49 kg. There was a significant association between weight loss and a reduction in A1C and FBG with exenatide only and a reduction in blood pressure for all therapies. Weight loss was associated with some improvements in lipids, primarily in the GLP-1 receptor agonist group, with little association in the insulin group.

Conclusions: Weight reduction with GLP-1 receptor agonists was associated with a shift toward a more favorable cardiovascular risk profile. Outcome trials are needed to determine whether improvement in biomarkers translates into a reduction in cardiovascular events in patients with type 2 diabetes.

Figure 1

Odds ratio and 95% CI of the association of weight loss (percentage from baseline) with any reduction in (A) A1C, (B) FBG, (C) SBP, (D) DBP, (E) triglycerides, (F) total cholesterol, or (G) LDL cholesterol and (H) increases in HDL cholesterol relative to no weight loss after adjustment for covariates.*P < 0.05, **P < 0.0001, compared with patients who did not lose weight. Orange, exenatide; green, sitagliptin; red, insulin.