Risks vs Benefits for SGLT2 Inhibitor Medications
Weight Loss
A study by Weber and colleagues found that the SGLT2 inhibitor dapagloflozin lead to a reduction in body weight from -1.0 kg to -0.3 kg compared with placebo.12 Cefalu and colleagues found that daily prescribing of 100 mg and/or 300 mg of canagliflozin evidenced dose-dependent loss of weight.13 Neeland and colleagues found that empagliflozin utilization resulted in less adiposity indices in 3,300 subjects.14
Albuminuria
Sodium-glucose cotransporter 2 inhibitors have a reno-protective role in patients with type 2 DM (T2DM). In those receiving renin-angiotensin blockers with T2DM and hypertension, dapagliflozin decreased their albuminuria.15 Canagliflozin has a similar potential.16 Empagliflozin reduced the urine albumin-creatinine ratio in patients with macro- or micro-albuminuria, supporting a direct renal effect by SGLT2 inhibitors.17
Systolic Blood Pressure
Sodium-glucose cotransporter 2 inhibitors can have beneficial effects on physiologic vascular outcomes. In patients with T2DM and hypertension, dapagliflozin reduced mean systolic blood pressure (SBP) compared with placebo: -7.3 mm Hg vs -10.4 mm Hg, respectively.12 Prescribing canagliflozin treatment at 100 mg or 300 mg reduced SBP (-4.3 mm Hg and -5.0 mm Hg, respectively, vs placebo at -0.3 mm Hg).18 Subjects taking empagliflozin 10 mg or 25 mg exhibited an adjusted mean BP change from baseline of -4.60 mm Hg and -5.47mm Hg, respectively, whereas placebo induced a -0.67 mm Hg decline.19
Risks
Nausea, fatigue, polyuria, polydipsia, and xerostomia are common SGLT2 AEs. Use of SGLT2 inhibitors can induce certain other more serious AEs as well.
Increased Risk for Amputations
The Canagliflozin Cardiovascular Assessment Study (CANVAS) and the Canagliflozin Cardiovascular Assessment Study-Renal (CANVAS-R) documented that canagliflozin doubled the incidence of leg and foot amputations in research participants compared with placebo (6.3 vs 3.4 per 1,000 patient-years).16 Therefore, canagliflozin should be prescribed with caution in persons with a prior history of foot ulceration, neuropathy, and/or vascular diseases.20
Acute Renal Injury
The mechanism of kidney damage by SGLT2 inhibitor drugs is not completely understood. About 100 patients experienced renal failure after the intake of SGLT2 inhibitor drugs.21 Among them, more than half reported symptom onset within a month of starting the medication, and their symptoms improved after discontinuing the SGLT2 medication. As a result, the FDA issued a warning to monitor renal function before initiating and during such pharmacotherapy.21
Ketoacidosis
Sodium-glucose cotransporter 2 inhibitors might lead to elevated ketone body levels22 and euglycemic ketoacidosis;23 however, this risk reportedly is negligible.24 Use of SGLT2 inhibitors is not recommended for patients evidencing the presence of precipitating factors like acute gastroenteritis or insulin pump failure.25
Genitourinary Infections
About 10% to 15% of women taking SGLT2 inhibitor medications developed urinary tract infections and vulvovaginitis.26 This could be because of a glycosuria effect caused by SGLT2 inhibitors.27
Hypotension
Sodium-glucose cotransporter 2 inhibitors cause contraction of intravascular volume. Therefore, patients taking SGLT2 inhibitors are at risk for hypotension, leading to dizziness and potentially dangerous falls. Patients already taking volume-depleting medications, such as diuretics, should be advised to use this group of medications with caution and report these AEs.28
