Where Do SGLT2 Inhibitors Fit in Diabetes Care?

New Class of Drugs 'Turns Glucosuria on Its Head'

Clifford J. Bailey, PhD


October 15, 2013

In This Article

Use at Any Stage of Type 2 Diabetes

How good are they? When do we use them? Because they have a non-insulin-dependent mechanism of action, in principle they should be able to be used at any stage during the natural history of type 2 diabetes. Let's look at the trials and see what comes out. From studies with the drugs that have been looked at in detail to date (dapagliflozin and canagliflozin) and the available data that are coming through with the other flozins (eg, empagliflozin), we can see a consistent reduction in A1c levels in essentially all of the trials. This is in the region, in most cases, of slightly less than 1%, occasionally a little more. Bear in mind, however, that these trials have been undertaken with baseline A1c levels of 8% or less, so we are seeing the values coming down to the 7% mark. In individuals who have much higher baseline A1c, we see quite a big fall in A1c, as we do with many antihyperglycemic agents.

The amount of glucose that is being excreted in the urine is on the order of 50-100 g daily. If you work on the principle of about 4 calories to the gram of glucose, that means that between 200 and 400 calories daily are excreted in the urine, so you might indeed expect there to be a weight loss. Most patients with type 2 diabetes are either overweight or obese, and therefore weight loss would be an advantage. Indeed, this is what we see with that amount of calories being eliminated in the urine -- typically somewhere between 2 and 3 kg of weight loss over 6 months. Like the A1c value, the effect appears to carry on and is evident in studies that have been extended to 1 and even to 2 years, and soon we will have data for the 3-year follow-up. We are getting reductions in glucose as well as reductions in weight.

The glucose that is eliminated in the urine is also going to create a small amount of osmotic diuresis in the region of 200-400 mL daily. If you divide that among all of a person's daily voids, it is a fairly modest and not really noticeable amount. However, it may have an effect within the body. These therapies all seem to reduce A1c, weight, and blood pressure similarly. In individuals who have high systolic blood pressures to start with (blood pressure 140 mm Hg or higher) one might expect to see a 5-mm Hg reduction in systolic blood pressure, and perhaps a 2-mm Hg reduction in diastolic blood pressure. When the blood pressure is at the lower-normal range, one would see very little effect on blood pressure. We don't see individuals developing hypotension. The mechanism may be more complicated than osmotic diuresis, but we will have to wait and see.


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