Abstract
The lowest dosage of empagliflozin (10 mg) showed similar benefits on glycated hemoglobin (HbA1c) level, body weight, blood pressure, and total and cardiovascular mortality in comparison with the highest available dose (25 mg) in the EMPAREG trial. These findings have not been clearly demonstrated for canagliflozin and dapagliflozin. The objective was to compare the effect of different doses of SGLT2 inhibitors commercially available in Brazil on HbA1c and body weight of patients with type 2 diabetes. MEDLINE, Cochrane and Embase databases were searched from inception until 11th October 2021 for randomized controlled trials of SGLT2 inhibitors in type 2 diabetes patients, lasting at least 12 weeks. HbA1c and body weight variations were described using standard mean difference. We performed direct and indirect meta-analysis, as well as a meta-regression with medication doses as covariates. Eighteen studies were included, comprising 16,095 patients. In the direct meta-analysis, SGLT2 inhibitors reduced HbA1c by 0.62% (95% CI -0.66 to -0.59) and body weight by 0.60 kg (95% CI -0.64 to -0.55). In the indirect meta-analysis, canagliflozin 300 mg ranked the highest regarding reductions in HbA1c and body weight. The remaining medications and dosages were clinically similar, despite some statistically significant differences among them. Canagliflozin 300 mg seems to be more potent in reducing HbA1c and body weight in patients with type 2 diabetes. The remaining SGLT2 inhibitors at different doses lead to similar effects for both outcomes. Whether these glycemic and weight effects are reflected in lower mortality and cardiovascular events is still uncertain and may be a topic for further studies.
Highlights
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antihyperglycemic medications that inhibit renal glucose reabsorption in the proximal convoluted renal tubule and lead to glucosuria [1-3]
The present study shows that SGLT2 inhibitors have similar effects on HbA1c and body weight regardless of the agent used and the employed dosage
All SGLT2 inhibitors at different doses were associated with genital mycotic infections, but not with bone fractures or urinary tract infection
Summary
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antihyperglycemic medications that inhibit renal glucose reabsorption in the proximal convoluted renal tubule and lead to glucosuria [1-3]. SGLT2 inhibitors have a beneficial effect on blood pressure (BP) and body weight [4-6]. Canagliflozin, dapagliflozin and empagliflozin are the three SGLT2 inhibitors currently approved by the Food and Drug Administration (FDA) for clinical use and the usual recommended doses are. In the EMPA-REG Outcome trial, a smaller dose of empagliflozin (10 mg) produced similar benefits on glycated hemoglobin (HbA1c) level, body weight and blood pressure in comparison with the highest available dose (25 mg) [8]. Data regarding canagliflozin and dapagliflozin at different doses are lacking, since the Canvas Trial failed to find separate. All SGLT2 inhibitors at different doses were associated with increased risk of genital mycotic infection (Supplemental Material – Figure 3S). As heterogeneity among trials was high, we performed a meta-regression using medication dose as a covariate, which did not explain the heterogeneity found.
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