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Success With New T2D Medications

CE / CME

Strategies for Clinical Success With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and GIP/GLP-1 Coagonists

ABIM MOC: maximum of 0.25 Medical Knowledge MOC point

Physicians: Maximum of 0.25 AMA PRA Category 1 Credit™

Released: November 07, 2023

Expiration: November 06, 2024

Jennifer B Green
Jennifer B Green, MD
CME/CE Information

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Key Takeaways
  • SGLT2 inhibitors can cause osmotic diuresis, natriuresis, and glucosuria. Setting patients up for success with this category of medication involves accounting for the diuretic effect with their existing medications and discussing methods of preventing genitourinary infections.
  • GI adverse effects are common with GLP-1 receptor agonists and GIP/GLP-1 receptor coagonists but can be mitigated through dietary modifications. It is important to understand how patients’ eating habits may affect their tolerance of these medications.

When we decide to use newer therapies, such as sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 coagonists for treatment of patients with type 2 diabetes, the goal, ultimately, is for patients to tolerate the medication and to stay on it long term. To achieve this, we must be mindful of the counseling and advice that we can provide to patients to help ensure success for these 3 classes of medication.

SGLT2 Inhibitors
If we first consider SGLT2 inhibitors, a key point that I think is important to discuss with patients is that the SGLT2 inhibitors can cause osmotic diuresis, natriuresis, and glucosuria.

Regarding the diuretic effect, I am careful to look at my patients’ existing list of medications before I start the new medication. I look for other diuretics and medications they are taking that may also have a diuretic effect. If they are receiving other diuretic medications, such as a thiazide diuretic, or if their blood pressure is low, I will often stop that medication when I add the SGLT2 inhibitor until I can understand what effect the new agent will have on their volume status. If needed, the other medications, such as the thiazide, can always be added back later for blood pressure management. However, in my experience, I often do not need to add back that baseline medication because the SGLT2 inhibitor fills that role very well.

The most common adverse effect of the SGLT2 inhibitors is an increase in risk of genitourinary (GU) infections because of their mechanism of increasing glucose in the urine. This is most likely to occur in women or in men who are uncircumcised. The good news is that if a person has a GU infection related to an SGLT2 inhibitor, it tends to happen within the first 6 months, will generally respond to usual treatments, and does not tend to recur in most individuals. However, it is still important to discuss with patients, so that they know that this might occur.

With my patients, I discuss simple clinical recommendations to reduce the likelihood of GU infections happening, including being sure to clean and dry that area well each day and patting dry after urinating, even if they are not in the habit of doing that. I might consider other options if a patient tends to have a lot of recurrent GU infections already or if they have a disability or other reason why they find it hard to ensure personal hygiene.

Another factor that may increase the risk of GU infections on SGLT2 inhibitors is a high A1C. If patients starting an SGLT2 inhibitor also have an elevated A1C, I would ensure that appropriate steps are being taken to control their blood sugar as well.

If patients develop GU infections while receiving an SGLT2 inhibitor, I do not usually stop the SGLT2 inhibitor while treating the infection. There is no evidence that discontinuing the SGLT2 inhibitor helps them recover more quickly. I usually will keep them on the SGLT2 inhibitor and treat them with an antifungal, most commonly a course of fluconazole.

GLP-1 Receptor Agonists and GIP/GLP-1 Coagonists
With GLP-1 receptor agonists and the new coagonist tirzepatide, my recommendations for clinical success and maximizing tolerability are very similar, so I will group these drugs together in my discussion.

In my opinion, it is best to start low and go slow with these medications. Personally, I always start patients on the lowest dose of a GLP-1 receptor agonist or tirzepatide.

Before we start, I counsel them on the most common adverse effects, which are gastrointestinal in nature. In my experience and in the clinical trials, we see that the most common gastrointestinal adverse effect reported is nausea. Much less common, fortunately, is vomiting. Patients may also experience either loose stools or constipation.

I think discussing common adverse effects before initiating a new medication is crucial for success because when patients know the expected adverse effects and understand that they will usually improve even as they continue the medication, they are less alarmed if they have that problem and are less likely to stop the medication.

Of course, I also make sure to let patients know if that their adverse effects are severe, they tell me immediately that that is happening.

I also recommend to not titrate the medication faster than the titration schedule recommended by drug manufacturers. Many patients will actually do better with a slower titration schedule. For example, if I have a patient on a given dose of a GLP-1 receptor agonist who is still feeling a little bit nauseated, I will wait until the patient is feeling completely better before I uptitrate to the next highest dose. I think it is also important to keep in mind that some patients simply cannot tolerate a higher dose—even if given ample time to acclimate—and need to stay on the lowest dose tolerable.

Of note, nutritional counseling sometimes can be very helpful in ensuring the tolerability of these agents. For example, in my area, people often do not eat breakfast and may not even eat lunch, with an enormous dinner being their main meal of the day. I tell them that is almost a guaranteed way to feel bad while receiving these medications. I encourage patients to spread out their food intake as evenly throughout the day as they can. I remind my patients that eating a very large meal or a meal very high in fat can greatly increase the likelihood of nausea. If patients have acid reflux, they might also need to avoid spicy foods, at least at first. Patients should be moderate with their alcohol intake as well.

It is possible to manage some adverse effects with medications, but I personally would prefer if my patients could make some dietary modifications to make them less of an issue.

For medications that can cause weight loss, such as GLP-1 receptor agonists, malnutrition can be a concern. Fortunately, in my patient population, malnourishment while receiving GLP-1 agonists and tirzepatide does not seem to be a problem. However, when people lose a significant amount of weight, they are losing both adipose tissue and muscle tissue. For certain individuals, that may not be desirable. In fact, losing a lot of muscle mass is not desirable for anyone. It is possible that a patient, perhaps an older person, is eating much less than usual while receiving the medication and is not consuming enough protein. In a case like this, I refer patients to a nutritionist to talk about protein intake and to make sure they are not malnourished. I also encourage some weight-bearing exercise or resistance training, if they are able, to help to minimize the adverse effects on muscle mass and strength.

Finally, I believe it is important to remember that people will be on GLP-1 receptor agonists or a coagonist for very long periods of time. What might be perfectly acceptable for patients at a given point in their lives might not be needed as they age. With that in mind, I think it is important for healthcare professionals to reassess our patients’ overall health status. The key is to practice good clinical judgment and respond to our patients’ changing needs.

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 type 2 diabetes and obesity. 

Your Thoughts?
What advice and counseling do you give patients who are starting one of these classes of medications? Have you found a particular strategy very helpful that is not mentioned here? Leave a comment to join the discussion.

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Poll

1.

A patient newly diagnosed with type 2 diabetes presents with an A1C of 8.5% and a history of recurrent urinary tract infections and obesity. The patient has an additional goal of weight loss (BMI 32 kg/m2). Which of the following is the best option for initial pharmacotherapy based on current guidelines?

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