Sodium glucose co-transport 2 inhibitors in the treatment of type 2 diabetes mellitus: a meta-analysis of randomized double-blind controlled trials

Abstract

BackgroundThe discovery of sodium-glucose co-transporter 2 (SGLT2) inhibitors, with a novel mechanism independent of insulin secretion or sensitization, bring about a new therapeutic approach to the management of type 2 diabetes mellitus. The aim of this meta-analysis was to evaluate the safety and efficacy of SGLT2 inhibitors at different doses in randomized double blind clinical trials.MethodsThis meta-analysis was conducted by including randomized double-blind controlled trials of SGLT2 inhibitors in patients with type 2 diabetes irrespective of their antidiabetic drug exposure history but with an inadequate glycemic control. All the effect sizes were computed using the random effects model. Standardized mean differences (SMDs) and odds ratios (OR) were computed for continuous and dichotomous variables, respectively. Additional analyses like sensitivity analysis, subgroup analysis and meta-regression were also performed.ResultsThe pooled analyses demonstrated a significant reduction in mean changes in Hemoglobin A1c (HbA1c) (SMD = −0.78%, 95% CI, -0.87 to −0.69), fasting plasma glucose (FPG) (SMD = −0.70 mg/dl, 95% CI, -0.79 to −0.61), body weight (overall SMD = −0.59 kg, 95% CI, -0.65 to −0.52) and blood pressure from baseline with SGLT2 inhibitors based therapy. Consistently a significant number of patients treated with SGLT2 inhibitors achieved HbA1c < 7% (OR = 2.09, 95% CI, 1.77 to 2.46). SGLT2 inhibitors based therapy was associated with adverse events like genital and urinary tract infections.ConclusionAll studied doses of SGLT2 inhibitors, either as monotherapy or in combination with other antidiabetic agents, consistently improved glycemic control in patients with type 2 diabetes. However, a small percentage of patients suffer from genital and urinary tract infections.

Luseogliflozin and other sodium-glucose cotransporter 2 inhibitors: no enemy but time?

“…High-density lipoprotein (HDL) levels were significantly increased from baseline (mean increase + 0.21 mg/dl), whereas there was no change in low-density lipoprotein (LDL) levels [11]. Conversely, both dapagliflozin and canagliflozin were associated with genital tract infections, whereas the former was also associated with urinary tract infections, both infections being more common among female participants [11]. Vasilakou et al [10] also inferred that a minimal increase in the risk of hypoglycaemia was noted in comparison to placebo, but SGLT2 inhibitors were at least as safe as the active comparator [10].…”

“…Furthermore, compared with placebo, the use of SGLT2 inhibitors was associated with significant reduction in fasting plasma glucose (FPG) (mean reduction -0.70 mmol/l), body weight (mean reduction -0.59 kg), systolic (mean reduction -0.27 mm Hg) and diastolic blood pressure (mean reduction -0.24 mm Hg) from baseline [11]. High-density lipoprotein (HDL) levels were significantly increased from baseline (mean increase + 0.21 mg/dl), whereas there was no change in low-density lipoprotein (LDL) levels [11]. Conversely, both dapagliflozin and canagliflozin were associated with genital tract infections, whereas the former was also associated with urinary tract infections, both infections being more common among female participants [11].…”

“…Vasilakou et al [10] also inferred that a minimal increase in the risk of hypoglycaemia was noted in comparison to placebo, but SGLT2 inhibitors were at least as safe as the active comparator [10]. Nonetheless, the number of patients who experienced serious adverse events or discontinued treatment due to adverse events did not differ significantly between SGLT2 inhibitors and placebo-treated patients [11].…”

“…However, no difference was found when comparison was made against active comparator as monotherapy (mean difference -0.05%), especially against metformin [10]. Furthermore, compared with placebo, the use of SGLT2 inhibitors was associated with significant reduction in fasting plasma glucose (FPG) (mean reduction -0.70 mmol/l), body weight (mean reduction -0.59 kg), systolic (mean reduction -0.27 mm Hg) and diastolic blood pressure (mean reduction -0.24 mm Hg) from baseline [11]. High-density lipoprotein (HDL) levels were significantly increased from baseline (mean increase + 0.21 mg/dl), whereas there was no change in low-density lipoprotein (LDL) levels [11].…”

“…Indeed, the safety and efficacy of these agents in T2DM have been thoroughly studied, both in randomised controlled trials and in systematic reviews and meta-analyses [7,[10][11][12][13]. Vasilakou et al [10] have recently demonstrated that the use of canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, luseogliflozin, tofogliflozin, ertugliflozin and remogliflozin was accompanied by a significant reduction in HbA 1c levels compared with placebo as monotherapy (mean difference -0.79%) or as add-on treatment (mean difference -0.61%), or against active comparator as add-on treatment (mean difference -0.16%).…”