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CKM risk factors and treatment
Reaching New Heights in CKM Care: The Latest in CKM Risk Factor Management and Treatment Optimization

Released: March 13, 2026

Jennifer Green
Jennifer Green, MD
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Key Takeaways
  • In patients with T2D, it is important that HCPs emphasize glycemic, blood pressure, and lipid management as well as the use of cardio-kidney protective therapies to address diabetes-related complication risks.
  • HCPs should consider early initiation of cardio-kidney protective therapies like SGLT2 inhibitors and GLP-1 receptor agonists in all patients with T2D, including those at lower risk for cardiovascular or kidney disease.
  • HCPs should expect some eGFR decline (≤30%) in patients with CKD who are started on ACE inhibitors, ARBs, or SGLT2 inhibitors, as this is an expected effect on kidney hemodynamics.

It is important for healthcare professionals (HCPs) to communicate the concept of cardiovascular–kidney–metabolic (CKM) syndrome to patients with CKM conditions. Furthermore, this education needs to be presented in a language that is appropriate and easily understood, so the average person can grasp the fact that these organs and systems are interconnected. HCPs also must consider the impact of disease or dysfunction on one organ/system and how that might affect others.

In my clinic, for example, we discuss the potential long-term consequences of diabetes with patients from the outset (either at the time of diagnosis or during their first clinic visit). Patients should understand that we are treating their diabetes, blood pressure, and lipids to keep their cardiovascular system, kidneys, and the rest of their body protected to the greatest extent possible from the adverse effects of diabetes and other metabolic conditions.

Another key principle that HCPs must communicate to patients is that the heart and kidneys, in particular, are connected and truly part of the same system. If the kidneys are not working properly, then there are bound to be adverse consequences that impact the heart and larger cardiovascular system. I think this is an easy link for people to make conceptually, but I choose to deliver that message in a more positive light. That is, many of the newly available therapies that help preserve kidney function over time also have been found to reduce the risk of heart failure or major adverse cardiovascular events (MACE). HCPs can do so by explaining to patients why they are prescribing these therapies—that they are used to protect the kidneys and benefit one’s cardiovascular health simultaneously. These are the important concepts to introduce into contemporary care.

Long-term Cardiovascular and Kidney Risk
Considering the high-impact actions that HCPs can take to reduce the long-term cardiovascular and kidney risks in patients with diabetes and/or metabolic syndrome, I will address metabolic syndrome first. Many patients likely have some degree of dysglycemia without a diabetes diagnosis. In my opinion, slowing the progression of prediabetes to diabetes, or perhaps preventing patients from developing diabetes altogether, is going to have the greatest metabolic impact. That is because diabetes is associated with a 2- to 4-fold increase in risk for adverse cardiovascular events and complications. One of the most effective ways to reduce progression from prediabetes to diabetes is weight management. For those with metabolic syndrome without diabetes, weight loss is likely to have the greatest and most meaningful impact.

Once patients develop type 2 diabetes (T2D), there are a variety of different tools we can use to address their CKM risk factors. I like to communicate these opportunities by showing my patients the Parthenon-like figure in the American Diabetes Association’s Standards of Care for managing the risk of diabetes complications. What this figure illustrates is that there are multiple strategies (or pillars) that we must employ to reduce the risk of diabetes-related complications; we cannot effectively reduce risk by only focusing on 1 pillar. These pillars comprise the management of hyperglycemia, blood pressure, and lipids as well as treatment regimens that include newer therapies with proven efficacy in reducing the risk of key cardiovascular and/or kidney outcomes that is independent of their glucose-lowering effects.

Again, there is not a single strategy that effectively reduces patients’ risk alone. For any given patient, it is likely that they will struggle to optimize the management of at least 1 pillar. Therefore, this provides HCPs the opportunity to help patients control the 3 other pillars as best as possible. For example, when patients are referred to endocrinology, it often is because they have a great deal of difficulty in managing their A1C. Within endocrinology clinics, generally, the mean A1C tends to be much higher than in the primary care setting. Although primary care HCPs can have a positive impact on patients’ glycemic control, not everyone can be brought to target in this setting. Furthermore, primary care’s responsibility also includes the management of blood pressure and lipids, as well as the selective use of cardio-kidney protective therapies. As an endocrinologist and for patients who struggle to get their A1C under 7%, I continue trying to achieve that goal with them, and I might double down on the implementation of the other risk reduction strategies to keep them healthy for as long as possible.

Early Initiation of Cardio-Kidney Protective Therapies
Early use of therapies like sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (RAs) in patients with diabetes is imperative. Remember, these therapies can be initiated from the outset in those with diabetes—across the board—for both glycemic control and favorable effects on weight. In today’s Standards of Care in Diabetes, glucose and weight management are given equal importance because excess weight is a pathophysiologic driver of T2D. It accelerates the progression or worsening of diabetes over time and independently increases the risk for several diabetes-related complications and comorbidities. That is why this approach should be taken for all patients with T2D, including those at lower risk.

An issue remains; the risks posed to recently diagnosed patients with T2D often are underappreciated. This is because HCPs in the US do not do a particularly good job of screening for potential cardiovascular or kidney disease in newly diagnosed patients. In particular, there is poor uptake among HCPs in monitoring urine–albumin-to creatinine ratio (UACR) annually in those with T2D, despite guideline recommendations to do so. Many of these patients will have evidence of kidney disease based on an elevated UACR at the time of diabetes diagnosis. This is because those with T2D often have hyperglycemia for an extended period of time and can have other independent risk factors for kidney and cardiovascular disease (ie, hypertension, dyslipidemia, and obesity) before they are diagnosed with T2D. Treating patients right away with therapies that provide cardio-kidney protection may, in fact, significantly reduce the risk of adverse outcomes among those who are fundamentally at higher risk early on than is readily appreciated today by HCPs.

A final note on this topic—most clinical trials that showed a benefit with the use of SGLT2 inhibitors or GLP-1 RAs were conducted in high-risk patients with T2D. That means enrolled patients either had kidney disease, established cardiovascular disease, or multiple risk factors for cardiovascular disease. That was for practical purposes because it is difficult to show significant risk reduction among those who do not have established disease or a heavy burden of risk of adverse events within the near future. But that does not mean that lower-risk patients will not benefit from treatment. There are data from the GRADE trial, which evaluated the effects of 4 glucose-lowering therapy classes added to metformin in patients without kidney disease and with T2D for an average of approximately 4 years. Cardiovascular outcomes data showed that patients treated with liraglutide plus metformin had a significantly reduced risk of MACE-5, MACE-6, and hospitalization for heart failure compared with all other groups combined, which included use of the insulin glargine, glimepiride, or sitagliptin plus metformin. Therefore, there are many reasons to think about the use of SGLT2 inhibitors and GLP-1 RAs early and at the time of diagnosis if considered appropriate for patients with T2D.

Strategies for Monitoring Kidney Function
When starting or intensifying cardio-kidney protective therapies in the outpatient setting, there certainly are some practical strategies that HCPs should follow and that help them assess the impact of these interventions. With any antihypertensives and lipid-lowering agents, HCPs must monitor the efficacy and potential toxicities related to each therapy. For kidney function specifically, you should monitor both estimated glomerular filtration rate (eGFR) and UACR at least annually in patients with chronic kidney disease (CKD). Of note, a significant reduction in UACR is generally a clear sign that the intervention has had a beneficial effect, including the slowing of CKD progression and reducing the risk of adverse cardiovascular events.

Now, volume status is a critical consideration when adding an SGLT2 inhibitor to patients’ regimen. A population in which I am careful about starting an SGLT2 inhibitor includes those with already well-controlled blood pressure, in whom I do not want to lower their blood pressure any further. For example, in a frail and older patient, perhaps their treatment regimen includes diuretic therapy. And remember, SGLT2 inhibitors have a diuretic effect, including both an osmotic diuretic effect and some natriuresis. If the patient’s blood pressure is well controlled and their volume status is a bit low, I usually discontinue their use of hydrochlorothiazide when adding an SGLT2 inhibitor. If they are on loop diuretics, I might decrease the dosage since the SGLT2 inhibitor will have a further independent diuretic effect. For patients in whom further blood pressure lowering or diuresis is not appropriate or necessary, HCPs should critically assess their existing antihypertensive and/or diuretic regimen. See if you can cut back on the therapies they are already taking to minimize the likelihood that they would become volume depleted or have a greater-than-expected reduction in eGFR with the addition of an SGLT2 inhibitor.

This is good, clinical common sense. It is much easier, if necessary, to add back the hydrochlorothiazide to control blood pressure after you have assessed the impact of the SGLT2 inhibitor on a patient’s volume status. I also find that I generally do not need to add back the hydrochlorothiazide for many patients because their blood pressure remains well controlled once I have substituted in the SGLT2 inhibitor. This is also a nice way to reduce patients’ pill and treatment burden; that is, look for opportunities to make substitutions with new therapies that have greater benefits when possible.

Strategies for Treatment Optimization
When treatment with an ACE inhibitor, ARB, or SGLT2 inhibitor is started, particularly in patients with CKD, there is often a transient drop in their eGFR. It is important to remember that this does not always represent an adverse effect on kidney function. In fact, the opposite is generally true. A modest decline in eGFR with the addition of these therapies often represents a favorable effect on intraglomerular or systemic hemodynamics rather than acute kidney injury. Furthermore, when adding these therapies to patients’ regimens for kidney protective reasons, nephrologists expect to see a reduction in eGFR. Of note, nephrologists do not initiate ACE inhibitors or ARBs with the goal of achieving good blood pressure control. Instead, they know that up-titration of these therapies to their maximally tolerated dose is what will effectively slow the worsening of kidney function over time.

I am an endocrinologist, but I have learned from my nephrology colleagues that a decline in eGFR of 30% or less actually represents a favorable effect on kidney hemodynamics and is expected to be kidney protective as well as cardioprotective over time. However, if you see patients’ eGFR decline greater than 30%, then you should be concerned about possible acute kidney injury and evaluate those patients accordingly.

Your Thoughts
How often do you prescribe cardio-kidney protective therapies like SGLT2 inhibitors and/or GLP-1 RAs in your patients with CKM conditions? You can get involved in the conversation by answering the poll question and posting a comment below.

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How often do you prescribe cardio-kidney protective therapies like SGLT2 inhibitors and/or GLP-1 receptor agonists in your patients with CKM conditions?

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