T2D Medications: Choosing the Right Patient

CME

Choosing the Right Patient: Optimizing Success With Newer T2D Medications

Physicians: Maximum of 0.25 AMA PRA Category 1 Credit

ABIM MOC: maximum of 0.25 Medical Knowledge MOC point

Released: November 15, 2023

Expiration: November 14, 2024

Carol Hatch Wysham
Carol Hatch Wysham, MD

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Key Takeaways
  • In addition to glucose management, newer T2D medications including SGLT2 inhibitors, GLP-1 receptor agonists, and GIP/GLP-1 coagonists have medical benefits for patients with T2D and comorbidities such as cardiovascular disease, heart failure, chronic kidney disease, and obesity regardless of their weight or glucose levels.
  • Healthcare professionals should consider a patient’s comorbidities and treatment targets when choosing a medication to treat T2D to provide the best medical benefit.

To ensure maximum success and results with newer type 2 diabetes (T2D) medications including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 coagonists, healthcare professionals first need to determine which patient would be appropriate for a particular drug. Although the degree of hyperglycemia must be considered, it is also important to know whether the person has additional comorbidities, such as atherosclerotic cardiovascular disease, heart failure (HF), chronic kidney disease (CKD), history of stroke, or a combination of these. With this information, we can decide which medication is going to give patients the best medical benefit regardless of their A1C.

Patients With T2D With Cardiovascular Risks
If I see a patient with HF, I will choose an SGLT2 inhibitor preferentially, as we have overwhelmingly good data with SGLT2 inhibitors and HF benefit and do not yet have outcomes data to suggest benefit with the GLP-1 receptor agonists.

In the absence of HF, if a patient has CKD with albuminuria, I also would select an SGLT2 inhibitor first, as we do not yet have strong data for benefit with GLP-1 receptor agonists in those patients. However, my decision would change if the patient needed significant A1C reduction. For example, a patient with CKD with an elevated A1C of 1.5% to 2.0% above their goal and a glomerular filtration rate of 50 mL/min/1.73 m2 would benefit from an SGLT2 inhibitor. However, because of the elevated A1C in this case, I would choose the GLP-1 receptor agonist or GIP/GLP-1 coagonist first to decrease the patient’s glucose levels and then add the SGLT2 inhibitor later if appropriate. In my experience, this helps to decrease the adverse events patients may experience with an SGLT2 inhibitor when glucose is higher.

When considering atherosclerotic cardiovascular disease, I think those patients without HF are likely best served by a GLP-1 receptor agonist because there are better data from multiple large cardiovascular outcomes trials on the prevention of myocardial infarctions and strokes with these agents. It is possible that GIP/GLP-1 coagonists also may confer benefit, but we do not yet have data from cardiovascular outcomes trials to determine if we can substitute a GIP/GLP-1 coagonist for this indication.

Patients With T2D With Other Comorbidities
In patients with T2D and obesity or those who need to lose weight because of other comorbidities, such as metabolic dysfunction‒associated steatotic liver disease or obstructive sleep apnea, there is obvious benefit in taking a medication that can help them manage both their T2D and weight. A GIP/GLP-1 coagonist or a GLP-1 receptor agonist therefore would be a good choice. The current American Diabetes Association guidelines recommend choosing an agent with high or very high efficacy for weight loss in patients for whom weight management is a target. Of the currently available agents, semaglutide and tirzepatide have the greatest efficacy for weight loss, and with the recent approval of tirzepatide for the treatment of obesity, both are now approved for the treatment of obesity in the absence of T2D.  None of the currently available agents is approved for metabolic dysfunction‒associated steatotic liver disease, but some studies suggest there may be some benefit. As more agents become available for treatment of T2D and its related comorbidities, patient preference should be included in treatment decisions.

Newer T2D Medications and Health Insurance
Unfortunately, insurance coverage is often a consideration when choosing therapy. If, for example, a patient would benefit from semaglutide but it is not covered by their insurance, I will push for it if they have a compelling indication, such as cardiovascular disease. However, liraglutide also is indicated to reduce the risk of major adverse cardiovascular events in patients with T2D, so that may be a reasonable alternative if we are unable to get semaglutide for the patient. Unfortunately, liraglutide does not reduce weight or A1C to the same magnitude that semaglutide does. I do find that if I believe the patient needs a particular agent because of comorbidities, clear documentation of the need for that agent improves the chance of it getting approved by the insurance company. Some plans may require the patient to try another agent in the same class, such as liraglutide first.

Getting Higher Doses of GLP-1 Receptor Agonists Approved for Patients With T2D
Although I mostly prescribe the lower T2D doses of GLP-1 receptor agonists rather than those approved for obesity treatment, I do have the occasional patient who has insurance coverage for the higher dose regardless of whether they have T2D. In these cases, I remind patients that they have T2D and the medication is indicated for T2D, but that the higher dose form also could be used—if it is appropriate in terms of their A1C—to provide additional weight loss benefits. If it is not covered by the patient’s insurance, you can try appealing the decision, which sometimes works. In patients without T2D, I will appeal, citing the patient’s BMI and serious comorbidities that indicate they really need to lose weight.

Final Thoughts
Other weight loss medications, such as phentermine/topiramate, offer almost the same weight loss as semaglutide and are available for a much more affordable price. They may still be too expensive for some patients, but they may provide an alternative for some. Therefore, the approach I take is to try to get the GLP-1 receptor agonist first, but if I cannot get it for the patient, then I let people know that there are other medications that have high efficacy, and we try that.

If you would like to learn more about these medications, click here to watch a short video describing the mechanisms of action of SGLT2 inhibitors, GLP-1 receptor agonists, and GIP/GLP-1 coagonists in T2D and obesity.

Your Thoughts?
In your practice, what advice and counseling do you give patients with T2D with comorbidities who would benefit from weight loss? Leave a comment to join the discussion.

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How frequently do you consider other comorbidities when choosing a medication for a patient with T2D?

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