#9 Novel Diabetes Therapy: SGLT2 Inhibitors

Overview

There is a diabetes epidemic in the United States. According to the Centers for Disease Control, 26 million children and adults—8.3% of the population—have diabetes, which is a defect in the body’s ability to convert glucose (blood sugar) to energy. Unfortunately, about seven million of them aren’t aware that they have this serious metabolic disorder. Another 79 million Americans have prediabetes, a precursor to this devastating disease that can cause a host of serious medical problems.

There is no cure for diabetes, although there are many ways of keeping diabetes under control. Treatments are designed to help the body regulate the sugar levels in the blood and prevent the development of long-term complications. Unfortunately, the optimal treatment of hyperglycemia—excess glucose in the bloodstream—in type 2 diabetes remains a major clinical challenge.

There are many diabetes medications, and most work by affecting the supply or use of insulin, which helps move glucose into the cells. But now there is now a new class of drugs ready for prime time called sodium-glucose co-transporter 2 protein inhibitors, or SGLT2 inhibitors. These drugs represent a paradigm shift in diabetes treatment because they reduce blood sugar in a totally new way: by causing it to be excreted during urination.

 When the protein SGLT2 is blocked after taking the once-a-day medication, a substantial amount of glucose flows out in the urine, and glucose levels soon drop. This is important because the kidneys naturally guard glucose very closely; it’s an evolutionary throwback to a time when meals were irregular and glucose was preserved as a vital source of energy. This is a major problem for people with diabetes today, because it directly contributes to their sustained elevated glucose levels.

The kidneys strive to keep urine glucose-free and only a tiny amount of glucose that is filtered by the kidneys is excreted in urine because sodium-glucose transport proteins make sure that it is reabsorbed back into the body. What the novel SGLT2 inhibitors do is block the return of high levels of glucose, allowing for its subsequent excretion.

Diabetes management often entails the use of multiple drugs for optimal control. While other diabetes mediations typically boost insulin levels or make the body more sensitive to insulin, SGLT2 inhibitors work independently of the hormone, leaving the door open for possible use as an add-on therapy.
Another advantage of this innovative treatment strategy is that with so many calories now lost during urination, the SGLT2 inhibitors also contribute to weight loss. This is a benefit because many people with diabetes are overweight and some diabetes medications they take contribute to their weight gain. Results of clinical trials with a SGLT2 inhibitor showed an average loss of five pounds compared to placebo over six months, as well as a reduction in blood pressure.

There are now many SGLT2 inhibitors in major clinical trials here and abroad, with one awaiting FDA approval in 2011. Study results have reported that the drugs are very effective after a few months of treatment and well tolerated, even among refractory patients. Responding well to this new therapy may offer hope for much improved diabetes management in an increasingly at-risk population both here in the United States and globally.
 

Where Are They Now

In 2015, the FDA issued an initial safety warning for this class of SGLT2 inhbiting drugs for type II diabetes patients, stating that these drugs have been found to lead to ketoacidosis, a serious condition where the blood becomes too acidic. The FDA will continue monitoring the situation to determine if dosing changes need to be implemented. However, sales of these drugs are still very successful and expected to increase by over 18-35% in the coming years, as the drugs have been linked to significant reduction in blood pressure and cardiovascular risk in patients with type II diabetes.

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