The Debate About SGLT-2 Inhibitors and GLP-1 Receptor Agonists

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and likewise, glucagon-like peptide-1 (GLP-1) receptor agonists, have been shown to be effective therapies in treating patients with type 2 diabetes. Additionally, the 2 classes of medicines have been linked to lower mortality than competing therapies, such as dipeptidyl peptidase 4 (DPP-4) inhibitors.

The results of some studies estimate that by 2050, 1 in 3 individuals in the United States will have type 2 diabetes. The excess of disease, then, will most likely result in a concurrent increase in common comorbidities such as cardiovascular disease, microvascular complications, hypertension, hyperlipidemia, and kidney disease. Coupled with those projections, these 2 classes appear to be a light of hope.

Yet, despite that several of these 2 medicines have proved to reduce adverse cardiovascular sequelae of diabetes, that has not been the case for all the options in their respective classes, and it is not particularly clear why that is. That, in turn, has led to some confusion for patients and providers alike.

At the American Diabetes Association's 78th Annual Scientific Sessions, Robert Gabbay, MD, PhD, the chief medical officer and senior vice president of the Joslin Diabetes Center, spoke with MD Mag about the controversies and debates surrounding SLGT-2s and GLP-1s—both classes of efficacious, but rather underused, medications.

Robert Gabbay, MD, PhD:

I think some of the confusion or controversy about both classes of drugs, SGLT-2 and GLP-1, is that in each case, there are various analogs. Some of the analogs have been demonstrated to have cardiovascular benefit, and some either have not yet been demonstrated and those trials are underway or perhaps because of study design or other factors—we don't really know—were not demonstrated to be beneficial from a cardiovascular [standpoint]. Not increase in cardiovascular risk, which is why all these studies were done in the first place, to assess safety, but whether they actually lower cardiovascular disease.

The biggest controversy, really, in both cases, is if these are class effects or individual to the drugs that were in the specific trials that demonstrated benefit. I think we'll know more as more these studies come out, particularly on the SGLT2 inhibitors. There are studies ongoing that are looking at the other agents and we'll know more as they come out.

In the GLP-1 [class], I think there clearly some that have shown benefit and others [that have not]. The debate, always, when you don't see a benefit is: was it that the study population was slightly different, or a number of study design factors that could explain it, or are the analogs actually different and they have different effects? I think it's that adds to some level of confusion in choosing them.

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