Abstract
Introduction: Although Canagliflozin, an FDA-approved sodium-glucose cotransporter 2 inhibitor (SGLT2i), is known to reduce body weight and blood pressure (BP) in the short-term, it is unclear whether this effect persists in the long-term. Furthermore, it remains uncertain whether the reduction in BP and body weight is dose-dependent. Objective: To conduct a meta-analysis to study the effects of long term Canagliflozin use on BP and body weight in type 2 diabetes mellitus (T2DM) patients and stratify the results by dosage. Methods: MEDLINE and Scopus were queried in May 2018 for randomized controlled trials (RCTs) of Canagliflozin that had a follow-up period of at least one year and reported change in BP and percentage change in body weight. Data from included studies were pooled using a random effects model and results were presented as weighted mean differences (WMDs) with 95% confidence intervals (CIs). Subgroup analysis according to dosage (100mg/300mg) was performed. Chi-squared test was conducted to test for subgroup differences. Results: Five RCTs (N=15,230 participants) were included in the final analysis. Canagliflozin also led to significant reduction in body weight when compared to controls (WMD: -3.32% [-4.04, -2.60]; p<0.001); however, this effect was not found to be dose-dependent (p=0.76). Both systolic (WMD: -4.40 mmHg [-5.18, -3.62]; p<0.001) and diastolic (WMD: -1.68 mmHg [-2.14, -1.23]; p<0.001) BP were significantly lower with long-term canagliflozin use, when compared to placebo (Figure 1). This effect was significantly stronger in the 300mg subgroup, when compared to the 100mg subgroup for both systolic (p=0.02) and diastolic (p=0.01) BP. There was no significant change in the risk of hypotension with the use of canagliflozin (Odds ratio: 1.59 [0.80, 3.19]; p=0.19). Conclusion: Long-term Canagliflozin is associated with reduced body weight and may be one mechanism for the beneficial BP response observed . Favorable changes in body weight and BP may be responsible for improved cardiovascular outcomes in T2DM patients with Canagliflozin.
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