Effects of different doses of canagliflozin on blood pressure and lipids in patients with type 2 diabetes: a meta-analysis

Abstract

Background: Canagliflozin is a sodium glucosecotransporter-2 receptor inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM). However, it is less prescribed due to increased LDL cholesterol (LDL-C), high incidence of urinary tract infection (UTI), high cost. Data on the effect of canagliflozin on blood pressure (BP) are also limited. We conducted a meta-analysis of randomized controlled trials (RCTs) to review dosedependent effects of canagliflozin on BP and lipids in patients with T2DM.Methods: A meta-analysis of RCTs in patients with T2DM was conducted. MEDLINE, the Cochrane Library of Trials and Clinicaltrials.gov were searched for relevant studies from January 2008 to May 2021.Results: Compared with placebo, canagliflozin 100 mg reduced SBP by 3.43 mmHg and DBP by 1.05 mmHg. Canagliflozin 100 mg increased LDL-C by 0.10mmol/l and HDL cholesterol (HDL-C) by 0.05 mmol/l. Compared with placebo, canagliflozin 300 mg reduced SBP by 4.75 mmHg and DBP by 1.69 mmHg. Canagliflozin 300 mg increased LDL-C by 0.16 mmol/l and HDL-C by 0.06 mmol/l. Compared with canagliflozin 100 mg, canagliflozin 300 mg further reduced SBP by 1.21 mmHg and DBP by 0.64 mmHg, and further increased LDL-C by 0.06 mmol/l and HDL-C by 0.02 mmol/l. Compared with placebo and canagliflozin 100 mg, canagliflozin 300 mg increased the risk of UTI. Conclusion:The current meta-analysis provides new evidence on different doses of canagliflozin as an antihypertensive agent in T2DM complicated by hypertension; however, LDL-C and the risk of UTI should be monitored.

Neutral effect of SGLT2 inhibitors on lipoprotein metabolism: From clinical evidence to molecular mechanisms

“…Different meta-analyses have evaluated the effects of SGLT2i treatment on lipid profile. A meta-analysis of studies in patients with T2DM treated with placebo or canagliflozin 100 mg or 300 mg confirmed the lipid-rising effects of this drug, with canagliflozin 300 mg producing the maximal increases in LDL-C (+6.19 mg/dL, +0.16 mmol/l) and HDL-C (+2.32, +0.06 mmol/L) (Table 2) [31]. Unfortunately, the possible influence of background lipid-lowering medications has not been evaluated.…”

The Effect of Canagliflozin on High-Density Lipoprotein Cholesterol and Angiopoietin-Like Protein 3 in Type 2 Diabetes Mellitus

“…Some studies have explored the efficacy of SGLT2 inhibitor in clinical trials in circulating lipids. A meta-analysis including studies in patients with T2DM treated with placebo or canagliflozin suggested that canagliflozin 300 mg produced the maximal increases in HDL-C [ 16 ]. Another study showed that dapagliflozin suppressed small dense LDL-c and increased HDL-2c, a favorable cardiometabolic marker [ 17 ], while there are some controversial results in LDL-c level with SGLT2 inhibitor treatment.…”

“…Some studies have explored the efficacy of SGLT2 inhibitor in clinical trials in circulating lipids. A metaanalysis including studies in patients with T2DM treated with placebo or canagliflozin suggested that canagliflozin 300 mg produced the maximal increases in HDL-C [16]. Journal of Diabetes Research…”

Effectiveness and Tolerability of the Intensification of Canagliflozin Dose from 100 mg to 300 mg Daily in Patients with Type 2 Diabetes in Real Life: The INTENSIFY Study

“…Direct comparisons between 100 mg of canagliflozin daily (CANA100) and CANA300 from phase 3 randomized clinical trials (RCTs) [ 11 , 12 ], as well as indirect comparisons of CANA300 with other SGLT-2is [ 13 , 14 ], have shown that CANA300 induces significantly greater reductions in HbA1c, weight, and systolic blood pressure (SBP) than its comparators. However, although CANA300 seems to show greater efficacy than CANA100, no RCT to date has evaluated the strategy of intensifying SGLT-2i therapy by increasing the dose from CANA100 to CANA300.…”