The drug, Invokana, just approved by the FDA will be sold by Johnson & Johnson. It treats patients with type 2 diabetes in a new way, by causing blood sugar to be excreted in the urine. Most of the existing type 2 drugs work by increasing the supply or affecting the use of insulin.
Invokana is in the class of drugs called SGL2 inhibitors. Sodium-glucose transporter-2 (SGLT2) 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, because a transporter in kidney cells, called SGLT2, reabsorbed glucose back into the blood to conserve energy. Glucose represents a major body fuel, so any loss of glucose into the urine would be wasteful.
Normally, glucose molecules pass from the bloodstream into an area of the kidney called the glomerulus and is then actively reabsorbed by SGLT2 (in an area called the proximal convoluted tubule), rather than being lost into the urine.
Two sodium-glucose co-transporters have been identified that cause the glucose to be reabsorbed: SGLT1 and SGLT2. One of these, SGLT2, which is found only in the proximal tubule of the kidney, accounts for most of the reabsorption of glucose.
The other, SGLT1 is also found in the gut and other tissues, but accounts for only about 10% of glucose 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, so returning the filtered glucose to the bloodstream is counterproductive.
It was exciting to find that some chemicals can actually block the activity of the SGLT transporters. Some medications, called SGLT inhibitors, block the action of the SGLT transporters, and the more selective SGLT2 inhibitors work only in the kidney. Loss of glucose into the urine from the activity of these SGLT2 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.
Several companies are evaluating different SGLT2 inhibitors in clinical trials.
What's especially intriguing about the SGLT2 inhibitors is that they do not intervene with glucose metabolism, so these drugs would be complementary to present approaches to glucose regulation. Invokana may be used alone or in conjunction with other diabetes drugs.
Clinical trials of Invokana have shown decreases in A1C with minimal side effects. 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. Invokana is not recommended for patients with severe kidney disease. One nice side effect routinely seen is a small amount of weight loss.