Diabetes Self-Management Blog

SGLT1 and 2 are proteins that move glucose out of the intestines and kidneys. Blocking them might keep glucose in the intestines and cause more glucose to be urinated out via the kidneys, lowering blood sugar levels. That’s what “SGLT inhibitor” drugs try to do. (Note: I’m not endorsing these drugs. I just find them really interesting and worth understanding.)

SGLT stands for sodium-glucose cotransporter. SGLT2 works in the kidneys, reabsorbing glucose from the urine back into the blood. If you inhibit SGLT2 with a drug, more glucose will be lost in the urine, and your blood sugar levels will go down.

SGLT2 inhibitor drugs called canagliflozin (brand name Invokana) and dapagliflozin (Farxiga) are already on the market. In studies, they lower A1C by about 1%. Because they increase urine output, they also seem to lower blood pressure a bit and cause weight loss averaging about 2 to 5 1/2 pounds. But very few studies have shown an A1C benefit of more than 1%.

Blocking SGLT2 only takes you so far. According to an article in Clinical Diabetes, SGLT2 inhibitors block only 30% to 50% of urine glucose from being reabsorbed. No one knows exactly why.

Perhaps other transporters are involved. A major one is SGLT1. It has a small effect on the kidneys and mostly works in the intestines to move glucose from food into the blood. So blocking SGLT1 action could reduce blood glucose by keeping it from getting into the blood so quickly.

A new study shows that inhibiting SGLT1 may lower blood glucose in several exciting ways.

Here’s how this may work. Many experts believe that refined flours and sugars and low-fiber diets fool our body. People have glands in the lower part of the small intestine (the distal ileum) that sense glucose and produce hormones called incretins. The best known incretin is glucagon-like peptide-1 (GLP-1). Incretins tell our bodies to produce insulin and get ready to work with it.

But modern refined foods are absorbed into the blood so quickly that the food never reaches the glands in the distal ileum. So our bodies don’t know to produce insulin and cells don’t know to be open to it. This may be a main cause of Type 2 diabetes.

SGLT1 does most of the glucose absorbing. So by inhibiting SGLT1, the glucose stays in the intestine, reaches the distal ileum, and stimulates production of GLP-1.

GLP-1 is the hormone that “incretin mimetic drugs” like exenatide (Byetta) and liraglutide (Victoza) mimic. One study showed that people who took a combined SGLT1 and SGLT2 blocker called LX4211 had GLP-1 levels that were higher (and glucose levels that were lower) after meals than they did before taking the medicine.

It may be that blocking SGLT1 and 2 together will lower blood glucose levels more. LX4211 looks promising in studies, but the studies were done by the developer, Lexicon Pharmaceuticals, so we must be cautious.

Not a cure
These are nice results, but note a few things. With LX4211, the A1C reduction was as much as 1.25%. That’s good, if there are few negative effects. But we don’t know that yet. These medicines haven’t been out long enough. And a 1.25% drop in A1C is not a cure. You still have to eat right and move your body.

Doctors have concerns about the SGLT2 inhibitors that are already out there, but physicians interviewed recently by Diabetes in Control seem increasingly in favor of using them. Some side effects, like bladder and vaginal infections, are happening less frequently than was feared.

The GLP-1 boosting effects of the SGLT1 inhibitor could probably be accomplished by eating more fiber every time we eat carbohydrate. Fiber will delay absorption until the carbohydrate reaches the distal ileum, triggering GLP-1, which triggers insulin.

The costs of these medicines can be considerable, over $9 a day, but that can often be avoided. When I checked, co-pays may be covered by the manufacturer for 12 months for Invokana, if you have private insurance to pay for the rest. Farxiga also offers 12 months of free co-pays, but says you can renew it year after year. (People using Medicare, Medicaid, TriCare, and other federally funded prescription programs aren’t eligible for either of these discount programs.)

So you might want to check them out. If any readers are taking SGLT2 inhibitors now, how are they working for you?

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