SGLT2 Inhibitors: Check Your A1c and BPs

Sodium glucose cotransporter 2 (SGLT2) inhibitors have a modest impact on A1c and, in some studies, have been shown to decrease blood pressure. The mechanism underling the latter effect is unclear but may be related to sodium loss. Here, one question on each topic.

What is the range of A1c reduction that has been described with monotherapy with SGLT2 inhibitors?

A. -0.1 to -0.3%

B. -0.6 to -1%

C. -0.9 to 1.2%

D. -1.2 to 1.5%

Click here for answer, discussion, and next question.

Answer: B. -0.6 to -1%.

The average A1c reduction is dose-dependent and varies based on the type of SGLT2 inhibitor used. However, in clinical studies to date, canagliflozin reduced mean A1c by 0.77% (100 mg dose) to 1.03% (300 mg dose) and dapagliflozin by 0.58% (2.5 mg dose), 0.77% (5 mg dose) and 0.89% (10 mg dose). Interestingly, in a study of cangliflozin in type 2 diabetes patients aged 55 to 80 years, those <65 years had a more robust A1c reduction (-0.65% and -0.82%) compared to those ≥65 years (-0.45% and -0.5%) for the 100 mg and 300 mg doses, respectively. Patients with moderately impaired renal function (GFR between 30-50 ml/min/1.73m2), however, responded with a lower A1c reduction compared to those with normal or mildly impaired renal function. This suggests that, because the drug acts in the kidney, there may be some heterogeneity by age and renal function that ought to be considered when the decision to use an SGLT2 inhibitor is made.

Which of the following parameters should be periodically monitored in patients with renal impairment who are on an SGLT2 inhibitor?

A. GFR

B. Serum potassium

C. Calcium

D. Blood pressure

E. A and B

F. B and D

Click here for answer and discussion.

Answer: F. Serum potassium (B) and blood pressure (D).

Because SGLT2 inhibitors induce osmotic diuresis, patients at risk for intravascular volume depletion (ie, elderly patients who may be on other antihypertensives) should be carefully monitored for symptomatic hypotension. In addition, the SGLT2 inhibitors’ action on a sodium-glucose transporter in the setting of renal impairment can affect serum potassium, magnesium, and phosphate levels. Serum potassium levels should be periodically checked, until a stable dose and stable renal function have been achieved.

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References:

Farxiga [package insert]. Princeton, NJ: Bristol-Meyers Squibb Company; 2014

Invokana [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2013.

Jardiance [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2014.