Background and aims: In clinical trials, incretin therapies improve glycemic control and cardiovascular (CV) risk factors such as blood pressure (BP) and lipids. GLP-1 agonists also produce weight loss (WL), and DPP-IV inhibitors are weight neutral. However, the effect of GLP-1 agonist-induced WL on glycemic control and CV biomarkers has not been examined in a large cohort database.
Materials and methods: We analyzed retrospectively the GE Centricity electronic medical records database to explore the association between WL and glycemic control, changes in BP, and changes in lipids in patients with type 2 diabetes (T2DM) who initiated exenatide (EXN), sitagliptin (SIT), or insulin (INS) in 2005-2007 in the United States. Patients had baseline and 1 yr follow-up data for body weight, A1C, fasting glucose (FPG), BP, total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG). Multivariate regression and correlation analyses were conducted, adjusting for baseline factors and outcome measures.
Results: A total of 6280, 5861, and 32,398 patients on EXN, SIT, and INS, respectively, were studied (baseline factors shown in the Table). Patients on EXN and SIT had WL (mean± SE) of 3.0±0.09 and 1.1±0.07 kg, respectively, whereas INS was associated with a slight weight gain (0.6±0.05 kg). WL was associated with reductions in BP in all groups (p<0.0001) and reductions of TG in the EXN and SIT groups (p<0.05). Moreover, EXN showed improvements in A1C, FPG (p<0.0001 both), TC (p<0.0001), and LDL-C (p=0.004), which were correlated with WL after multivariate adjustment. There was no correlation with WL and A1C and FPG for SIT, and correlations were negative with INS (p<0.0001). EXN patients who lost ≥4.5 kg were more likely to achieve A1C<7% with an adjusted odds ratio [OR] of 2.01[95% CI 1.52, 2.67] compared with those who lost no weight; where this OR was 1.39 [1.00,1.93] and 1.50 [1.25,1.80] for SIT and INS; respectively.
Conclusion: Thus, in a large cohort of patients with T2DM, even a small degree of WL was associated with significant improvement of BP. Furthermore, GLP-1 agonists provided additional benefits on lipids when WL was ≥4.5 kg, and significant incremental benefits in glycemic control were associated with WL. Therefore, the greater WL associated with GLP-1 agonists and its associated improvement in glycemic control, BP, and lipids may convey long-term CV benefits in T2D.
