Division of Endocrinology
Department of Medicine
Icahn School of Medicine at Mount Sinai
New York, New York
Zachary T. Bloomgarden, MD, MACE, has disclosed that he has received consulting fees from AstraZeneca, Boehringer Ingelheim, Merck, Novartis, and Sanofi and has ownership interest in Humana, Johnson & Johnson, and Novartis.
When treating patients with type 2 diabetes, the paramount goal is to control blood sugar. Fortunately, newer agents allow us to do that in a fashion that’s associated with additional benefits of weight loss, lipid improvement, blood pressure lowering, and addressing the entire spectrum of cardiovascular outcomes. To this end, my approach is to use the most effective treatment possible, which is why GLP-1 receptor agonists are my “go-to” drugs for treating diabetes in 2020.
The Case for GLP-1 Receptor Agonists
I prefer GLP-1 receptor agonists for several reasons, but primarily because they are highly effective at controlling blood sugar in a broad category of patients.
For example, in patients with decreased kidney function, the glycemic benefit of the GLP-1 receptor agonists is greater than other drug classes such as the SGLT2 inhibitors. With careful monitoring, GLP-1 receptor agonists can be given to patients with a low glomerular filtration rate (GFR) (< 30 mL/min), including end-stage renal disease, whereas the SGLT2 inhibitors should not be administered to patients with a GFR < 45 mL/min.
The efficacy of GLP-1 receptor agonists in the setting of renal impairment is important because many people with diabetes—particularly older patients, who constitute the majority of people living with diabetes in the United States—have decreased kidney function, and chronic kidney disease is a major cause of mortality in patients with diabetes.
The GLP-1 receptor agonists have also demonstrated benefit for patients with atherosclerotic cardiovascular disease. The mortality benefit has been well documented, including reductions in stroke and myocardial infarction. Moreover, this class of drugs is associated with a greater degree of weight loss than other drugs.
GLP-1 receptor agonists require daily or weekly injections, depending on the agent, but for patients who prefer to avoid injections we have oral semaglutide.
In addition, there are known issues with gastrointestinal intolerance in patients receiving GLP-1 receptor agonists. Most can be managed by providing a sympathetic explanation to patients about how the mechanism of action of these drugs leads to these side effects. However, patients with renal impairment who experience nausea, vomiting, diarrhea, and/or dehydration should be closely monitored because of a risk for worsened renal function.
Exceptions to the Rule
There are 2 clear exceptions to my preferential use of GLP-1 receptor agonists. For patients with macroalbuminuria and those with heart failure, particularly heart failure with reduced ejection fraction, I would choose SGLT2 inhibitors.
Although patients with these comorbidities typically make up a limited fraction of people living with diabetes, they are at very high risk from these complications and it is critical to match them with the ideal treatment. In these cases, the data clearly demonstrate that SGLT2 inhibitors are protective against adverse renal and cardiovascular outcomes. (However, when it comes to SGLT2 inhibitors, I no longer use canagliflozin because of an increased risk for amputation observed in the CANVAS trials.)
Conversely, for the general population of patients with diabetes, ie, those without macroalbuminuria or heart failure, we do not have evidence to support any greater benefit of SGLT2 inhibitors over GLP-1 receptor agonists.
Choosing Among GLP-1 Receptor Agonists
Once I have decided to use a GLP-1 receptor agonist, how do I choose between the available agents? I encourage you to visit the online decision support tool, Choosing Among GLP-1 Receptor Agonists for Patients With Type 2 Diabetes, which I developed with my colleagues, Martin J. Abrahamson, MD, FACP; Anne Peters, MD; Richard E. Pratley, MD; and Robert S. Zimmerman, MD. In this CME/CE-certified decision support tool, you can enter the details of your case and learn how 5 experts would proceed.
What is your “go-to” treatment for patients with type 2 diabetes? Answer the polling question and leave a comment in the discussion section.