Treating the Obese Diabetic

Julia Kenkre; Tricia Tan; Stephen Bloom


Expert Rev Clin Pharmacol. 2013;6(2):171-183. 

In This Article

Sodium–Glucose Cotransporter 2 Inhibitors

These inhibitors are very new to the market, and as such their role in diabesity treatment is not yet clear. They work by promoting urinary excretion of glucose by preventing its tubular reabsorption via the sodium–glucose cotransporter. While they have not yet been approved by the US FDA, one agent in the class, dapagliflozin, has recently been approved for use in Europe as an adjunct to diet and exercise in combination with other glucose-lowering agents, including insulin, and as a monotherapy for metformin-intolerant patients.[43]

Sodium–glucose cotransporter 2 (SGLT2) inhibitors are associated with weight loss. The initial weight loss seen is secondary to a mild osmotic diuresis, but in the longer term, this effect is ascribed to a reduction of fat mass, secondary to a caloric loss via glucose excretion in urine.[44] In a RCT of dapagliflozin added on to metformin treatment, a significant reduction in mean HbA1c was seen at 24 weeks in the dapagliflozin group (0.67% in the 2.5 mg group, 0.7% in the 5 mg group and 0.84% in the 10 mg group) along with a significant reduction in bodyweight (2.2, 3.0 and 2.9 kg, respectively, versus placebo loss of 0.9 kg).[45]

The most frequently reported adverse events include constipation, diarrhea, nausea, urinary frequency and genitourinary infections. Long-term safety data are lacking in this class of agents.