Type 2 Diabetes: Optimizing SGLT-2 Inhibitor Selection

Experts Javier Morales, MD, and Dhiren Patel, PharmD, CDE, BC-ADM, BCACP, consider the optimal use of respective SGLT-2 inhibitors to manage type 2 diabetes given safety and efficacy profiles and the potential need to intensify SGLT-2 inhibitor therapy.

Javier Morales, MD: The decision of when to implement the use of a dipeptidyl peptidase-4 (DPP-4) inhibitor versus a sodium—glucose cotransporter 2 (SGLT-2) inhibitor winds up being a discussion between you and the patient and also needs to take into consideration the patient’s overall status. When we look at what an SGLT-2 inhibitor has to offer relative to a DPP-4 inhibitor, an SGLT-2 inhibitor may have a beneficial effect on overall circulating volume because it does have a thiazide-like diuretic effect. It may also have a beneficial effect on systolic blood pressure reduction. Looking at the more recent publications, cardiovascular outcomes and safety have proven to be beneficial. However, when looking at the DPP-4 inhibitors, they tend to be more weight neutral. Patients won’t lose any weight on these agents. The benefit is that there will be no hypoglycemic events unless you’re using it in combination with the secretagogue or insulin, but they offer no effect whatsoever on blood pressure reduction that’s meaningful.

However, they do prove to be efficacious, and they do offer around a 0.4% to 0.6% reduction in glycated hemoglobin A1C. For some patients, that may be enough in order to get them to their proscribed target. The SGLT-2 inhibitors, however, do offer a little bit better efficacy. For those patients who may have a higher hemoglobinA1C may reap the benefit of additional A1C lowering.

Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: There are 4 SGLT-2 inhibitors that are currently on the market and a few more that are in development. The 4… on the market are empagliflozin, dapagliflozin, canagliflozin, and most recently approved one, ertugliflozin. You have 4 different SGLT-2 inhibitors that are on the market, and there are quite a few differences among them. From a higher level, adverse reactions of those drugs are actually very different, and I’ll share 1 example.

With canagliflozin, there’s a specific box warning regarding an amputation risk, which doesn’t exist with the others. Other differences include renal dosing. They all have different renal cutoffs, and depending on the prescription or what you’re counseling that patient on, it’s going to be important to look at their renal function because that’s going to dictate the dose you put the patient on.

Other differences include that cardiovascular data are different among them, and they have different labeled indications. I’ll share an example there. Specifically, with empagliflozin there is a label claim regarding cardiovascular death and the benefit there from a cardiovascular standpoint, which doesn’t exist with any of the other medications as of right now.

Javier Morales, MD: Most of the SGLT-2 inhibitors in the marketplace today usually come in 2 dose administrations: a lower dose and a higher dose. You have 4 different agents in the marketplace, with more to come. The decision of which agent to use should be individualized. Initially following the EMPA-REG trial, which wound up being a revolutionary study, it was decided that those patients at a higher risk of cardiovascular event rates would benefit from being on a medication like Jardiance, or empagliflozin.

However, more recent data from cardiovascular studies demonstrate that there was cardiovascular benefit in those patients who were on dapagliflozin, or Farxiga. The CANVAS study, which looked at the agent Invokana [canagliflozin], also showed benefit from a cardiovascular endpoint. They all tend to be beneficial, and I think what drives most practitioners nowadays in which agent to use is really going to be the insurance company and the coverage that they may offer. When it comes to the SGLT-2 inhibitors, however, there are no head-to-head studies between these agents that demonstrate that one may be more efficacious than the other. That needs to be taken into consideration when making an appropriate decision choice.