Value of SGLT-2 Inhibitors in Type 2 Diabetes

Experts Javier Morales, MD, and Dhiren Patel, PharmD, CDE, BC-ADM, BCACP, elucidate the value of SGLT-2 inhibition in the management of type 2 diabetes and reflect on the clinical tolerability of available agents in this setting.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: [Sodium—glucose cotransporter 2] (SGLT-2) inhibitors work by inhibiting a protein called the SGLT-2 protein, which is responsible for about 90% of reabsorption of glucose back into the circulation. Through this mechanism and through this inhibition, the excess glucose is excreted through the urine, and it hits one of the core defects of type 2 diabetes that has not been previously targeted through other drugs that we’ve had on the market.

One of the biggest benefits of using an SGLT-2 inhibitor is that it hits a core defect when we look at the different defects that are responsible before hypoglycemia in a patient with type 2 diabetes are examined. We’ve had medications that have targeted various core defects, but the defect that has not been targeted until this class became available is in the kidneys. We know a lot of glucose reabsorption takes place, so this medication class specifically targets that and allows excess glucose through the urine.

The feedback that I’ve received regarding SGLT-2 inhibitors has been quite positive. As pharmacists it’s important to explain the benefits of the class but also some of the adverse events that could be associated with it. In terms of some of the benefits that patients will see beyond just the glycemic benefits might include some weight loss associated with the drug class or some blood pressure reduction. Patients who have a history of heart failure have seen some benefit there, as well as patients who have any type of renal impairment. We’ve seen improvement in albuminuria.

But by the same token, there are some adverse events that we should counsel patients on, and those include infections. Patients could experience urinary tract infection or mycotic infections in both men and women. Most recently we’ve seen some commercials for SGLT-2 inhibitors, and patients have been coming to me and asking, “Hey, I saw this on TV. Can you tell me a little bit more about it?” That has been regarding some of the amputation risks that have been specifically associated with one of the agents. Again, there are some differences among the class, so it’s important to understand those differences and talk to your patients based off of that tailored regimen that the patient might be on.

Javier Morales, MD: Most of these agents have been found to be quite user-friendly for the patient In fact, most patients do report satisfactory results in terms of their A1c lowering. In addition to that, they do like the fact that they wind up shedding a couple of pounds when they’re on the SGLT-2 inhibitors. Unfortunately, there is an increased risk of mycotic genital infections, particularly amongst women and uncircumcised men. There are many things that could be recommended that might be beneficial such as drinking a little bit more water and trying to avoid things like barrier protection.

However, there are really no data looking at vitamin or mineral supplementation or probiotics in terms of trying to minimize these events. It winds up being a little bit of a challenge, however, to the practitioner in patients who may be experiencing urogenital symptoms and may be on an SGLT-2 inhibitor. It could be a bacterial urinary tract infection, or it could be a mycotic. If it’s treated as a bacterial urinary tract infection, the mycotic infection will likely worsen. And likewise, a lack of appropriate treatment for a potential bacterial urinary tract infection could lead to problems later on down the road. Most patients do find it quite easy to use, and it has been quite welcomed by the population in general.