Sodium-glucose transporter-2 (SGLT-2) is the name of a transporter protein in the kidneys that has been a hot topic in diabetes research. In people with normal blood glucose (BG) levels, glucose is not excreted into the urine. The glucose molecules pass from the bloodstream into an area of the kidney called the glomerulus and are actively reabsorbed by SGLT-2 (in an area called the proximal convoluted tubule), rather than being lost into the urine, into the blood to conserve energy. Glucose represents a major body fuel, so any loss of glucose into the urine would be wasteful.
Another sodium-glucose cotransporter, SGLT-1, is also found in the gut and other tissues but accounts for only about 10% of glucose reabsorption. SGLT-2 accounts for most of the remaining reabsorption. In people with diabetes and elevated blood glucose levels, the SGLT transporters function just the same as in folks with normal BG levels: they encourage glucose that was going to be flushed out in the urine to reabsorbed into the bloodstream. That’s counterproductive, as the BG is too high already.
Some medications, called SGLT-2 inhibitors, block the action of the SGLT transporters, and the more selective SGLT-2 inhibitors work only in the kidney. Loss of glucose into the urine from the activity of these SGLT-2 inhibitor drugs causes both the BG levels and the A1c to fall. Despite the increase in urinary glucose excretion and increased urinary volume, most participants in clinical trials have not complained of excessive urination. Clinical trials have shown than SGLT-2 inhibitors do not intervene with glucose metabolism, so these drugs would be complementary to present approaches to glucose regulation.
Invokana is an example of an SGLT-2 inhibitor. Invokana may be used alone or with other diabetes drugs. Clinical trials of Invokana have shown decreases in A1C with minimal side effects. A recent study showed that people using Invokana had 30% lower risk of end stage kidney disease, worsening kidney function, and kidney or heart-related death. Reported side effects include constipation and diarrhea, nausea, reports of hypoglycemia when used with sulfonylureas or insulin, and some women have developed vaginal infections (high glucose concentration in the urine allow yeast organisms to flourish). SGLT2 inhibitors may affect other blood constituents, and cause higher serum levels of magnesium, phosphate, and hematocrit. Renal function, apparently, is not disturbed.
Other SGLT-2 Inhibitors:
- Invokana (canaglifozin)
- Farxiga (dapaglifozin)
- Jardiance (empagliflozin)
- Steglatro (ertugliflozin)