Efficacy and Safety of SGLT2 Inhibitors Quiz

Test your knowledge of recent findings in SGLT2 inhibitor efficacy and safety research.

1. The degree of HbA1c reduction by canagliflozin (an SGLT2 inhibitor) is independent of baseline HbA1c.

True

False

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Answer: False

Based on data presented at the European Association for the Study of Diabetes (EASD) meeting in Vienna in September 2014, although all levels of HbA1c demonstrated efficacy in response to drug dose, the degree of reduction of HbA1c depended on the baseline HbA1c. In a placebo-controlled trial, those with HBA1c ≥9% achieved an HbA1c reduction of -1.25% (100 mg dose) or -1.48% (300 mg dose) compared with those with HbA1c <8%, who only achieved a reduction of -0.45% (100 mg) or -0.65% (300 mg) vs. placebo. This study found no difference in level of HbA1c reduction when stratifying by duration of diabetes. Therefore, this drug, which has an entirely insulin-independent mechanism, may be a great second-line agent, regardless of duration of disease or baseline HbA1c.

Reference: Cerdas S, et al. Glycaemic efficacy of canagliflozin by baseline HbA1c and known duration of type 2 diabetes mellitus. EASD Meeting, Vienna, Austria. 16-19 Sept. 2014.

2. The effects of SGLT2 antagonists include which of the following?

A. Genital infections

B. Decrease insulin release

C. Reduction in microalbuminuria

D. A and C

E. All of the above

F. None of the above

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Answer: D, A and C.

SGLT2 antagonists have an entirely insulin-dependent mechanism. However, by leading to glycosuria (which is the mechanism by which these drugs lower blood glucose), they do result in an increase in genital infections, with women having a higher incidence of this adverse effect compared to men. Recent data on empagliflozin presented at EASD examining pooled data from 458 type 2 diabetic patients with pre-existing microalbuminuria (<300 mg/day) at baseline on background of RAAS inhibition therapy. Differences in demographics as well as baseline degree of microalbuminuria were adjusted for in the models. The authors report that both doses of empagliflozin (10 mg and 25 mg) were associated with a reduction in microalbuminuria vs. placebo of 27 mg (10 mg dose) and 29.3 mg (25 mg dose). This study is one of the first demonstrations of a reno-protective effect of this class of agents (as opposed to the concern for this class of agents that glucosuria may damage renal vasculature).

Reference: Cherny D, et al. Sodium glucose cotransporter 2 inhibition with empagliflozin reduces microalbuminuria in patients with type 2 diabetes. EASD Meeting, Vienna, Austria. 16-19 Sept. 2014.

3. Which of the following are concerns when using SGLT2 inhibitors in elderly patients?

A. Pre-existing hypertension

B. Increased risk of fractures

C. Neurocognitive effects and worsening of dementia

D. None of the above

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Answer: B, Increased risk of fractures.

The data is not yet definitive, however, there are studies that suggest that treatment with SGLT2 inhibitors may increase risk of fractures as compared to placebo due to its effects on phosphate and parathyroid hormone. One small study (n=85) of those receiving 5 mg dapagliflozin over 104 weeks showed a bone fracture rate of 9.4% vs. 6.0% in the placebo group. Another pooled analysis of 8 clinical trials with a mean duration of 68 weeks of canagliflozin suggested a ~30% increase in the rate of bone fractures. The mechanism of this early signal may result from the increase in serum phosphate (due to increased tubular resorption) with a possible secondary increase in parathyroid hormone. There is also evidence that, via changes in FGF23, SGLT2 may decrease concentrations of 1,25-dihydroxyvitamin D.

Reference: Taylor SI, et al. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015 Jan;3(1):8-10. Epub 16 Dec 2014.