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Abstract
Anti-diabetic drugs for effectively lowering glucose with limited side effects are necessary in providing patient-centered diabetic management. Sodium glucose cotransporter 2 (SGLT 2) inhibitors provide a novel therapeutic approach for managing type 2 diabetic patients by lowering glucose levels by increasing urinary excretion of glucose independently of insulin secretion or action. Several SGLT 2 inhibitors were recently approved and available in the US, European and Korean markets. SGLT 2 improved glycemic control with low propensity of hypoglycemia. Through the clinical trials, most SLGT2 inhibitors were generally well tolerated. Genital tract infections were more frequent in most clinical studies of SGLT2 inhibitors and urinary tract infections were slightly increased in some studies. This review will describe the main safety issues that have been uncovered in clinical trials of SGLT 2 inhibitors.
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Table 1.
Adverse events of special interest associated with sodium glucose cotransporter 2 (SGLT2) inhibitors.
| Study design | Duration, wk | Reference | Hypoglycemiaa, % | Genital infection %a, % | Urinary tract infectiona, % |
|---|---|---|---|---|---|
| Dapagliflozin | |||||
| Monotherapy (vs. placebo) | 24 | [4] | 0–3 (3) | 8–13 (1) | 5–13 (4) |
| Add-on to metformin (vs. placebo) | 24 | [5] | 2–4 (3) | 8–13 (5) | 4–8 (8) |
| Add-on to pioglitazone (vs. placebo) | 24 | [7] | 0–2 (0) | 7–8 (3) | 4–8 (6) |
| Add-on to glimepiride (vs. placebo) | 24 | [6] | 7–8 (5) | 4–7 (1) | 4–7 (6) |
| Add-on to insulin (vs. placebo) | 48 | [8] | 54–60 (52) | 6–11 (3) | 8–11 (5) |
| Add-on to metformin (vs. glipizide) | 52 | [9] | 3.4 (39.7) | 12.3 (2.7) | 5.9 (7.6) |
| Canagliflozin | |||||
| Monotherapy (vs. placebo) | 26 | [10] | 3–4 (3) | 6–7 (2) | 5–7 (4) |
| Add-on to metformin + sulfonylurea (vs. placebo) | 26 | [12] | 27–30 (15) | 10–11 (3) | 6 (5) |
| Add-on to insulin (vs. placebo) | 18 | [13] | 49 (37) | 7–9 (1) | 2–3 (2) |
| Monotherapy (vs. glimepiride) | 52 | [20] | 5–6 (34) | 9–11 (5) | 6 (5) |
| Monotherapy (vs. sitagliptin) | 52 | [11] | 43 (41) | 12 (2) | 4(6) |
| Empagliflozin | |||||
| Monotherapy (vs. placebo) | 12 | [14] | 0 (1.2) | 0–3.7 (0) | 1.2–2.5 (1.2) |
| Add-on to metformin (vs. placebo) | 24 | [15] | 1.4–1.8 (0.5) | 3.7–4.7 (0) | 5.1–5.6 (4.9) |
| Add-on to insulin (vs. placebo) | 12 | [16] | 36.1 (35.3) | 5.2-7.7 (1.8) | 11.6-14.8 (8.8) |
| Add-on to metformin + pioglitazone (vs. placebo) | 24 | [29] | 1.2-2.4 (1.8) | 3.6-8.5 (2.4) | 11.9-17.0 (16.4) |
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