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Effect of Hemoglobin A1c Reduction or Weight Reduction on Blood Pressure in Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Treatment in Type 2 Diabetes Mellitus: A Meta-Analysis.
Hu, M, Cai, X, Yang, W, Zhang, S, Nie, L, Ji, L
Journal of the American Heart Association. 2020;(7):e015323
Abstract
Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have shown their beneficial effects on cardiovascular outcomes and multiple cardiovascular risk factors, including hypertension. However, the mechanism of blood pressure (BP)-lowering effects of these agents has not been elucidated. This study aims to evaluate the effect of hemoglobin A1c reduction or body weight reduction with GLP-1RA treatment and SGLT2i treatment on BP changes in patients with type 2 diabetes mellitus. Methods and Results Studies were identified by a search of MEDLINE, EMBASE, and the Cochrane Central Register until June 2019. Meta-regression analysis was performed to evaluate the association between hemoglobin A1c reduction or body weight reduction and changes of BP. A total of 184 trials were included. Both GLP-1RA and SGLT2i led to significant reductions in systolic BP (weighted mean difference, -2.856 and -4.331 mm Hg, respectively; P<0.001 for both) and diastolic BP (weighted mean difference, -0.898 and -2.279 mm Hg, respectively; P<0.001 for both). For both drug classes, hemoglobin A1c reduction was not independently associated with systolic BP reduction or diastolic BP reduction. In GLP-1RA treatment, weight reduction was positively associated with systolic BP reduction and diastolic BP reduction (β=0.821 and β=0.287, respectively; P<0.001 for both). In SGLT2i treatment, weight loss was significantly associated with systolic BP reduction (β=0.820; P=0.001) but was not associated with diastolic BP reduction. Conclusions Treatment with GLP-1RA and SGLT2i led to significant reductions in BP in patients with type 2 diabetes mellitus. Weight reduction was significantly and independently associated with BP reductions in GLP-1RA treatment and SGLT2i treatment.
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The Association Between the Dosage of SGLT2 Inhibitor and Weight Reduction in Type 2 Diabetes Patients: A Meta-Analysis.
Cai, X, Yang, W, Gao, X, Chen, Y, Zhou, L, Zhang, S, Han, X, Ji, L
Obesity (Silver Spring, Md.). 2018;(1):70-80
Abstract
OBJECTIVE Sodium glucose cotransporter 2 (SGLT2) inhibitors may induce urinary glucose excretion via the inhibition of renal glucose reabsorption, improve glycemic control, and lower body weight. The aim of this meta-analysis was to evaluate weight changes in patients who received different dosages of SGLT2 inhibitors. METHODS Overall, 55 placebo-controlled trials were included. RESULTS The results indicated that treatment with 2.5 mg, 5 mg, 10 mg, and 20 mg of dapagliflozin led to significant decreases in body weight compared with a placebo (weighted mean difference [WMD], -1.30 kg, -1.51 kg, -1.79 kg, -2.24 kg, respectively; P < 0.001). Treatment with 50 mg, 100 mg, 200 mg, and 300 mg of canagliflozin also led to significant decreases in weight (WMD, -1.20 kg, -1.82 kg, -1.83 kg, -2.37 kg, respectively; P < 0.001). In the treatment with empagliflozin, ipragliflozin, tofogliflozin, and luseogliflozin, body weight also significantly decreased. The decrease in weight was associated with the dosage of dapagliflozin (P < 0.05). CONCLUSIONS Body weight significantly decreased in patients with type 2 diabetes who received different dosages of SGLT2 inhibitors compared with patients who received a placebo. Moreover, in patients treated with dapagliflozin, there was a statistically significant dosage-dependent trend in body weight reduction.
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Comparisons of weight changes between sodium-glucose cotransporter 2 inhibitors treatment and glucagon-like peptide-1 analogs treatment in type 2 diabetes patients: A meta-analysis.
Cai, X, Ji, L, Chen, Y, Yang, W, Zhou, L, Han, X, Zhang, S, Ji, L
Journal of diabetes investigation. 2017;(4):510-517
Abstract
AIMS/INTRODUCTION To evaluate the efficacy of weight changes from baseline of the sodium-glucose cotransporter 2 (SGLT2) inhibitors treatment and glucagon-like peptide-1 (GLP-1) analogs treatment after comparisons with a placebo in type 2 diabetes patients, and the associated factors. MATERIALS AND METHODS Studies were searched from when recording began, June 2004, until June 2015, and re-searched in July 2016, and placebo-controlled randomized trials in type 2 diabetes patients with a study length of ≥12 weeks were included. RESULTS A total of 97 randomized controlled trials were included. Compared with a placebo, treatment with SGLT2 inhibitors was associated with a significantly greater decrease in weight change from baseline (weighted mean differences -2.01 kg, 95% confidence interval -2.18 to -1.83 kg, P < 0.001). Compared with a placebo, changes with GLP -1 treatment were also associated with a comparable decrease in weight change from baseline (weighted mean differences -1.59 kg, 95% confidence interval -1.86 to -1.32 kg, P < 0.001). Meta-regression analysis showed that the baseline age, sex, baseline glycated hemoglobin, diabetes duration or baseline body mass index were not associated with the weight change from baseline in SGLT2 inhibitors or in GLP-1 treatment corrected by placebo. Comparisons of weight changes from baseline corrected by placebo between SGLT2 inhibitors and GLP-1 treatment showed that the difference was not significant (P > 0.05). CONCLUSIONS According to the present meta-analysis, treatment with SGLT2 inhibitors and treatment with GLP-1 analogs led to comparable weight changes from baseline, which are both with significance when compared with placebo treatment.
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Metabolic effects of fluoxetine in adults with type 2 diabetes mellitus: a meta-analysis of randomized placebo-controlled trials.
Ye, Z, Chen, L, Yang, Z, Li, Q, Huang, Y, He, M, Zhang, S, Zhang, Z, Wang, X, Zhao, W, et al
PloS one. 2011;(7):e21551
Abstract
BACKGROUND The prevalence of obesity and diabetes is increasing dramatically throughout the world. Studies have shown that excess adiposity is a critical predictor of new onset T2DM. This meta-analysis is aimed to assess the metabolic effects of fluoxetine in T2DM. METHODS AND FINDINGS Electronic search was conducted in the database Medline, PubMed, EMBASE, and the Cochrane library, from inception through to March 2011. A systematic review of the studies on the metabolic effects of fluoxetine in T2DM was performed. The weighted mean difference (WMD) and its 95% CI were calculated from the raw data extracted from the original literature. The software Review Manager (version 4.3.1) and Stata (version 11.0) were applied for meta-analysis. Five randomized, placebo-controlled trials were included in the meta-analysis. According to WMD calculation, fluoxetine therapy led to 4.27 Kg of weight loss (95%CI 2.58-5.97, P<0.000 01), 1.41 mmol/L of fasting plasma glucose (FPG) decrement (95%CI 0.19-2.64, P = 0.02) and 0.54 mmol/L of triglyceride (TG) reduction (95%CI 0.35-0.73, P<0.000 01) compared with placebo. Moreover, fluoxetine therapy produced 0.78% of HbA1c decrement (95%CI -0.23-1.78). However, this effect was not statistically significant (P = 0.13). CONCLUSIONS Short period of fluoxetine therapy can lead to weight loss as well as reduction of FPG, HbA1c and TG in T2DM.