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SGLT2i for Cardio Renal Metabolic Disease
Do It Better: Managing Cardio–Renal–Metabolic Disease Early Improves Patient Outcomes

Released: August 14, 2025

Jay H. Shubrook
Jay H. Shubrook, DO, FACOFP, FAAFP
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Key Takeaways
  • It is critical to do a complete lab workup of patients with suspected cardio–renal–metabolic disease to fully understand their needs and effectively manage them with pharmacotherapy.
  • SGLT2 inhibitors offer blood pressure and glucose-lowering benefits to patients with type 2 diabetes in addition to significant renal protective benefits for those with comorbid chronic kidney disease.
  • Healthcare professionals should use their pharmacy colleagues and others to assist in titrating, monitoring, and managing adverse events to help patients reach their health goals sooner. 

A patient presents to your clinic with type 2 diabetes (T2D). She received metformin alone for the first 5 or 6 years after her diagnosis, but then her A1C started to rise, as many patients with type 2 diabetes experience. She saw another healthcare professional (HCP) who prescribed a GLP-1 receptor agonist, and the patient took it multiple times. She felt very sick on it and was unhappy with her weight loss, even though she had an obese status. The patient stopped the GLP-1 receptor agonist and received and started insulin.

The patient is now receiving 40 units of basal insulin and metformin 1000 mg twice daily, but her A1C remains elevated at 8.2%. The patient also needs to receive knee surgery, but the HCPs in charge of that will not let her get the surgery unless she lowers her A1C. Before the patient presented to your office, she had labs completed with the following results: Estimated glomerular filtration rate (eGFR) is 60 mL/min/1.73 m2, urine albumin–to-creatinine ratio is 68 mg/g, lipids are well controlled with a high-intensity statin, and blood pressure is well controlled with lisinopril 5 mg daily (an angiotensin-converting enzyme [ACE] inhibitor).

Identifying Cardio–Renal–Metabolic Disease
When thinking about the available treatment choices for this patient, the first necessary component is lowering her A1C. HCPs also should recognize that the patient has an unidentified complication because she has albuminuria. Based on her current labs, she has stage G2A2 chronic kidney disease (CKD). If her eGFR further decreases to 55 mL/min/1.73 m2, she would have stage G3a A2 CKD. And upon asking the patient if anyone previously told her that she has kidney trouble, she responded that she was unaware of this, even though she had elevated albuminuria. That is a whole thing in and of itself.

As I think about treating this patient, I know that she needs a small to moderate reduction in her A1C. Furthermore, she has at least 1 diabetes-related complication: CKD. When thinking about treatment choices, we could maximize her ACE inhibitor or switch to an angiotensin II receptor blocker, but her blood pressure is well controlled already. We could use a GLP-1 receptor agonist, but the patient told us that she did not tolerate previous treatment with this class of agents. Therefore, an SGLT2 inhibitor is an excellent choice for this patient. The American Diabetes Association 2025 guidelines recommend that we consider making room for an SGLT2 inhibitor for a person with T2D and CKD.

Before starting an SGLT2 inhibitor, HCPs should always have the same set of questions ready for patients who are new to this class. For example, do the patients have a history of urinary tract or yeast infections? Have they had glycemic decay before? What therapies have they tried that they did not tolerate well?

With our patient case, she does not have a history of urinary tract or yeast infections. She has an A1C that is moderately elevated, and other therapies that we would consider were not previously tolerated well. The choice is then left at basal insulin plus bolus insulin (or basal–bolus insulin therapy); basal insulin, metformin, plus a dipeptidyl peptidase-4 inhibitor; or basal insulin, metformin, plus an SGLT2 inhibitor. What would you do next?

In my opinion, because of the patient’s albuminuria, the addition of an SGLT2 inhibitor is the preferred treatment approach. A dipeptidyl peptidase-4 inhibitor would help lower her A1C, but it will not provide a significant protective kidney benefit to the extent that SGLT2 inhibitors do. Basal–bolus insulin therapy would help lower her A1C too, but there is no additional protective kidney benefit with this therapy. And because the patient does not have any contraindications, she is a good candidate for an SGLT2 inhibitor even though her blood pressure is normal.

Addressing Gaps in Cario–Renal–Metabolic Disease
Before we initiated additional therapy, the patient was unaware of the complete complexity of her current condition. Thank goodness she needed surgery. Because of that, she received a consultation, and HCPs were able to do the proper testing to get the complete picture of her condition.

Often, we think of SGLT2 inhibitors as “glucoretics,” with many HCPs only using these therapies if there is a need for a fair amount of glucose or blood pressure lowering. Regarding our patient case, we did not need to lower her blood pressure, but she did need additional help with lowering her A1C. This also needed to happen in a relatively quick time period so that the patient could receive her knee surgery. Therefore, there was a gap in evaluating the entirety of the risk for this patient.

I also think that many HCPs are nervous about adding an SGLT2 inhibitor to patients’ treatment regimens because of concerns of adverse events. Although many people think of urinary tract infections and genital candidiasis, other potential adverse events could include dehydration or hypotension. If you are nervous about using this class of agents, you can always start patients on a lower dose and titrate up. For the patient case here, I recommend initiating the SGLT2 inhibitor at the full dose to maximize the glucose lowering. However, the lower dose will provide the same kidney protection.

In addition, we know that the level of glycolysis can be affected by the level of hyperglycemia. The patient has moderate hyperglycemia, so I would not expect a great amount of fluid loss or blood pressure drop. This can be an issue of the glucose routinely >200 mg/dL or hemoglobin A1C >10%. I also would not be worried about the new glycemic decay because she has T2D and is receiving insulin. We might need to reduce her insulin dose a little bit because we are starting another glucose-lowering agent. However, I believe that this presents an excellent opportunity to implement more frequent blood glucose monitoring or continuous glucose monitoring via a sensor, which the patient would qualify for because of her insulin use.

Many people forget that SGLT2 inhibitors can decrease one’s eGFR soon after initiation. Understand that you should not be worried about an eGFR change early on, as there will be a predicted drop in eGFR that will improve over time. And you should see an improvement in the albuminuria in as early as 3 months. HCPs can recheck that even sooner, too. There is no required monitoring when you start an SGLT-2 inhibitor unless the patient has unstable hemodynamics.

Early Intervention With a Multidisciplinary Care Approach
As we think about cardio–renal–metabolic disease, remember that cardiovascular disease, heart failure, and CKD are closely tied together. Kudos to the HCP who saw the patient before we did and tried to address her need for weight loss with a GLP-1 receptor agonist.

If we decided to use basal–bolus insulin therapy, it probably would have increased the patient’s weight. It would have done nothing to help her cardio–renal–metabolic disease. This patient case illustrates the opportunities that HCPs will see in their practice, which include prescribing a therapy that will have benefits that go beyond lowering A1C alone for T2D. Because I am mindful of patients’ blood pressure, I often work with my pharmacy team and ask, “We are going to start X therapy, so would you mind checking in with the patients to see how they are feeling, and are they completing blood pressure checks every 2 weeks? Can you confirm that they are tolerating their therapy or if they are having any trouble? And then can you help me titrate the agent?”

If I start patients on a lower dose, my pharmacy team can then decide if we need to titrate up. If patients’ blood pressure lowers, this is then a judgment call. I probably would keep our patient on the SGLT2 inhibitor. In the future, I also might use an angiotensin II receptor blocker instead of an ACE inhibitor.

There are times when we do not need a lot of monitoring in certain patient cases. The thing that HCPs should watch for most is a change in eGFR. There is also a potential risk for hypokalemia with SGLT2 inhibitor use, as a low frequency of events is reported in trials. However, treatment with a concomitant ACE inhibitor could balance that out.

This is the time when you can collaborate with your other HCP team members, including pharmacists, to provide more supportive and comprehensive care. They can help you maximize patients’ therapy so that we do not spend 3 months on each step. And therefore, at 3 months, we can help patients achieve their goals instead. There is particularly good evidence showing a therapeutic benefit of early A1C reduction leading to decreased risk of cardiovascular complications with SGLT2 inhibitors.

Your Thoughts
How often are you prescribing SGLT2 inhibitors in your practice? You can get involved in the discussion by answering the poll question and posting a comment below.

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