Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus: A real-world experience

Abstract

Background: Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are a class of drugs with modest antidiabetic efficacy, weight loss effect, and cardiovascular benefits as proven by multiple randomised controlled trials (RCTs). However, real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.

Aim: To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.

Methods: We evaluated the comparative efficacy data of 3 SGLT-2i drugs (dapagliflozin, canagliflozin, and empagliflozin) used for treating patients with type 2 diabetes mellitus. Data on the reduction of glycated hemoglobin (HbA1c), body weight, blood pressure (BP), urine albumin creatinine ratio (ACR), and adverse effects were recorded retrospectively.

Results: Data from 467 patients with a median age of 64 (14.8) years, 294 (62.96%) males and 375 (80.5%) Caucasians were analysed. Median diabetes duration was 16.0 (9.0) years, and the duration of SGLT-2i use was 3.6 (2.1) years. SGLT-2i molecules used were dapagliflozin 10 mg (n = 227; 48.6%), canagliflozin 300 mg (n = 160; 34.3%), and empagliflozin 25 mg (n = 80; 17.1). Baseline median (interquartile range) HbA1c in mmol/mol were: dapagliflozin - 78.0 (25.3), canagliflozin - 80.0 (25.5), and empagliflozin - 75.0 (23.5) respectively. The respective median HbA1c reduction at 12 months and the latest review (just prior to the study) were: 66.5 (22.8) & 69.0 (24.0), 67.0 (16.3) & 66.0 (28.0), and 67.0 (22.5) & 66.5 (25.8) respectively (P < 0.001 for all comparisons from baseline). Significant improvements in body weight (in kilograms) from baseline to study end were noticed with dapagliflozin - 101 (29.5) to 92.2 (25.6), and canagliflozin 100 (28.3) to 95.3 (27.5) only. Significant reductions in median systolic and diastolic BP, from 144 (21) mmHg to 139 (23) mmHg; (P = 0.015), and from 82 (16) mmHg to 78 (19) mmHg; (P < 0.001) respectively were also observed. A significant reduction of microalbuminuria was observed with canagliflozin only [ACR 14.6 (42.6) at baseline to 8.9 (23.7) at the study end; P = 0.043]. Adverse effects of SGLT-2i were as follows: genital thrush and urinary infection - 20 (8.8%) & 17 (7.5%) with dapagliflozin; 9 (5.6%) & 5 (3.13%) with canagliflozin; and 4 (5%) & 4 (5%) with empagliflozin. Diabetic ketoacidosis was observed in 4 (1.8%) with dapagliflozin and 1 (0.63%) with canagliflozin.

Conclusion: Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c, body weight, and better than those reported in RCTs, with low side effect profiles. A review of large-scale real-world data is needed to inform better clinical practice decision making.

Keywords: Albumin creatinine ratio; Canagliflozin; Cardiovascular disease; Dapagliflozin; Diabesity; Empagliflozin; Sodium glucose cotransporter-2 inhibitors; Type 2 diabetes mellitus.

Figure 1

Changes of glycated hemoglobin from baseline at 6 months, 12 months, and latest with various sodium glucose cotransporter 2 inhibiting agents: Dapagliflozin, canagliflozin, and empagliflozin. HbA1c: Glycated hemoglobin.

Figure 2

Weight changes, from baseline to latest follow up period with dapagliflozin, canagliflozin, and empagliflozin.

Figure 3

Boxplots showing latest weight, with dapagliflozin, canagliflozin, and empagliflozin in male and female patients. SGLT2: Sodium glucose cotransporter 2; F: Female; M: Male.

Figure 4

Trends in the urine albumin creatinine ratio among patients with baseline microalbuminuria (urine albumin creatinine ratio ≥ 3 mg/mmol). ACR: Albumin creatinine ratio.

Figure 5

Boxplot analyses of baseline glycated hemoglobin vs diabetic ketoacidosis risk in individual sodium glucose cotransporter 2 inhibitor drugs at baseline and after 12 months. A: Box plot explanatory data analysis of baseline glycated hemoglobin (HbA1c) as a risk factor for diabetic ketoacidosis (DKA) with individual sodium glucose cotransporter 2 inhibitor (SGLT2i) drug showing a correlation between the two variables; B: Box plot data analysis of HbA1c level at 12 months as a risk factor for DKA with individual SGLT2i drug showing a correlation between the two variables. DKA: Diabetic ketoacidosis; HbA1c: Glycated hemoglobin; SGLT2: Sodium glucose cotransporter 2.