Dose-ranging effects of SGLT2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis

Arch Endocrinol Metab. 2022 Mar 8;66(1):68-76. doi: 10.20945/2359-3997000000440.

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.

Keywords: SGLT2 inhibitors; meta-analysis; type 2 diabetes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Blood Glucose
  • Body Weight
  • Brazil
  • Canagliflozin / therapeutic use
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents* / therapeutic use
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Canagliflozin

Grants and funding

this work was funded by CAPES, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) no. 307015/2010-6 and Fundo de Incentivo à Pesquisa of Hospital de Clínicas de Porto Alegre. C.B.L. is a recipient of a scholatship from CNPq (PQ-2).