Chronic kidney disease (CKD) is a significant complication present in over 40% of people with type 2 diabetes mellitus (T2D).1,2 The combination of T2D and CKD enhances the risk of developing kidney failure, atherosclerotic cardiovascular disease (ASCVD), heart failure, cardiovascular (CV) death, and all-cause mortality, thus highlighting the importance of risk management.3,4 Comprehensive care should include the management of diabetes, albuminuria, hypertension (HTN), and dyslipidemia with a combination of lifestyle interventions and pharmacotherapy with proven kidney and CV outcomes (Table 1).4 In most clinical trials, kidney outcomes are evaluated through a composite of end-stage kidney disease onset, sustained decrease in estimated glomerular filtration rate (eGFR) >40% to 57% from baseline, or renal death.5 The article will provide an overview of CKD management with a focus on people with T2D and CKD not on dialysis.
Because early stages of CKD are often asymptomatic, diabetes care and education specialists (DCESs) can play an active role in screening people with diabetes at risk for CKD in order to facilitate early diagnosis and management.4 Screening has been shown to be cost-effective in people with diabetes and is recommended at least annually for all people with diabetes, starting at diagnosis for those with T2D.5,6 Clinical practice guidelines recommend screening for CKD using both eGFR and a spot urine albumin-creatinine-ratio (UACR), ideally with an early morning void.5,7 eGFR is automatically calculated and reported with a basic metabolic panel, and several estimating equations are used in practice with variable accuracy and bias. The CKD-EPI 2021 creatinine equation refit without race is recommended as the initial assessment of kidney function. This equation should be prioritized over other available equations due to its acceptable performance without disproportionately affecting any one group of individuals.8 The use of UACR in the early stages of CKD is especially important as eGFR may remain high.9 Unfortunately, screening is underutilized, and less than half of people with T2D are screened for albuminuria annually, highlighting an opportunity for DCESs to optimize care.4
CKD diagnosis is made through the presence of either a decrease in eGFR, defined as <60 mL/min/1.732, or an abnormality in the kidney’s structure or function for at least 3 months. A number of kidney abnormality markers may be noted when making a CKD diagnosis, such as structural, histologic, urine sediment, and electrolyte abnormalities, and the presence of albuminuria tends to be the most common in adults.10,11 In addition to the diagnosis, further guidance and evaluation should be based on the clinical history and physical examination. Additional effort is taken to stage CKD based on eGFR, albuminuria, and the cause of CKD, which primarily drives outcomes, such as kidney failure.11 There may be a high degree of variability in eGFR and albuminuria, and those with abnormal results should have further screening for confirmation of CKD diagnosis.5,12
People with diabetes and CKD should be managed in a comprehensive, holistic, patient-centered approach to improve overall health outcomes.4,13 This approach requires a combination of lifestyle and pharmacotherapy interventions aimed at optimizing blood pressure (BP) and glycemic control in addition to aggressive management of cholesterol (Table 1). Together, there are 2 primary goals of comprehensive care: (1) reduce the risk of CKD progression and (2) prevent cardiovascular disease.13 Because of the complexity and resources typically required for managing diabetes and CKD concomitantly, incorporating a coordinated multidisciplinary treatment will improve structured education, shared decision-making, and promotion of self-management.4,13
Lifestyle interventions address diet, exercise, smoking, and weight. People with diabetes and CKD should consume an individualized and balanced diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts but low in processed meats, refined carbohydrates, and sugar-sweetened beverages.11,13 General targets of sodium (<2 g/d) and protein (0.8 g/kg/d) intake should be in accordance with the general population.11,13 The recommendation for physical activity consists of at least 150 minutes per week of moderate to intense physical activity and avoidance of sedentary behavior.11,13 People with T2D and overweight or obesity are recommended to achieve and maintain at least 5% weight loss through diet, physical activity, behavioral therapy, and in some cases, pharmacotherapy.14 However, neither the ADA Standards of Care nor Kidney Disease: Improving Global Outcomes (KDIGO) guidelines state specific weight loss goals for people also with CKD.
The standard glycated hemoglobin (A1C) goal for most people with CKD is less than 7%, but A1C should be individualized based on the risks and benefits of intensive glycemic control.5,13 Additionally, the accuracy and precision of A1C levels decrease with advancing CKD.13 Daily glucose monitoring with continuous glucose monitoring or self-monitoring of blood glucose may be useful. First-line treatment for most people with CKD, T2D, and eGFR ≥30 mL/min/1.73m2 is both metformin and a sodium-glucose cotransporter-2 inhibitor (SGLT2i). Additional therapy, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs), may be added to achieve individualized glycemic targets.5,13
Statin therapy is the mainstay treatment for primary and secondary prevention of ASCVD in people with diabetes and CKD.5,13 According to the 2024 ADA Standards of Care, in people ages 40 to 75 years at higher CV risk, including those with one or more ASCVD risk factors, high-intensity statin therapy is recommended.5 Because CKD is considered an ASCVD risk factor, most people with diabetes and CKD should receive a highintensity statin. Nonstatin therapy may be used in the setting of statin intolerance or when additional lowering of low-density lipoprotein cholesterol is needed.5,13
BP goals in people with CKD differ slightly between the 2024 ADA Standards of Care and 2022 KDIGO Diabetes in CKD guideline. The ADA Standards of Care recommend to target a BP level <130/80 mmHg.5 Lower or higher BP goals may be considered in some people based on the risks and benefits.5,13 Renin-angiotensin system inhibitors (RASis), either an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, are first-line treatment in people with diabetes and CKD and concomitant HTN and albuminuria.5,13 The recommendation for use is strongest in people with severely increased albuminuria (≥300 mg/g creatinine). Along with the BP lowering effects, RASis are preferred in this patient population based on the benefits in reducing albuminuria and slowing CKD progression. As a result, these medications should be titrated to the highest approved dose that is tolerated regardless of BP control.13 If albuminuria is not present, a dihydropyridine calcium channel blocker or thiazide diuretic may also be considered.5,13
The 2022 KDIGO Diabetes in CKD guideline recommends SGLT2i as first-line therapy in patients with T2D and CKD.13 The recommendation is independent of glycemic control and based on evidence demonstrating significant benefits in reducing CKD progression and CV risk in people with T2D and CKD.15-17 EMPA-KIDNEY and DAPA-CKD specifically enrolled a wide-range CKD population with or without T2D and showed benefit regardless of diabetes status.15,16 The 2024 KDIGO Evaluation and Management of CKD guideline now reflects these findings and recommends SGLT2i in patients with CKD with or without diabetes.11 Additionally, a stable dose of RASi was an inclusion criteria for these kidney outcome trials; however, based on guideline recommendations, it is not a requirement for people with T2D and CKD to be on a RASi prior to initiating SGLT-2i.13,15-17
It is important to note that although the glucose-lowering effect of SGLT2i weakens at lower eGFR levels, kidney and CV benefits of SGLT2i are still present. As a result, SGLT2i can be initiated in people with T2D and CKD in an eGFR as low as 20 mL/min/1.73m2.13 Once initiated, these agents can be continued even if the eGFR drops below 20 mL/min/1.73m2.13 It is recommended to discontinue therapy once dialysis or kidney transplant therapy is initiated owing to limited data evaluating the use of SGLT2i in these populations.13
Steroidal mineralocorticoid receptor antagonists (MRAs) have been shown to reduce albuminuria and BP but have not otherwise demonstrated a significant reduction in CKD progression.18 Nonsteroidal MRAs (ns-MRAs) have a high selectivity for mineralocorticoid receptors in the heart and kidney with less off-target effects than steroidal MRAs. Finerenone is currently the only ns-MRA with FDA approval. It has proven clinical kidney and CV benefits based on 2 phase 3 clinical trials in people with at least moderately increased albuminuria (UACR ≥30 mg/g) and a wide range of eGFR.19,20 Notable exclusions include heart failure with reduced ejection fraction and uncontrolled HTN. Finerenone is indicated for persistent albuminuria despite maximally tolerated RASi in people with CKD and T2D.4 Few patients in the trials were on concomitant SGLT2i, and therefore, it is reasonable to add finerenone after SGLT2i or in patients unable to use SGLT2i. For those indicated for RASi, SGLT2i, and finerenone, all cause initial hemodynamic decreases in eGFR, and thus initiating medication in a sequential manner should be considered. Patients must have an eGFR ≥25 mL/min/1.73m2 and normal potassium to initiate therapy. Finerenone may be continued until dialysis or kidney transplant as long as the drug is tolerated.13 The use of MRAs with RASi is limited by additive hyperkalemia, and finerenone is no exception.
GLP-1 RAs are a therapeutic class growing in importance and preference for those with CKD and T2D, as evidenced by its strong recommendation behind SGLT-2i and metformin.13 GLP-1 RAs have several compelling benefits in managing T2D, lowering the risk of CV events, and chronic weight management.5 Furthermore, most GLP-1 RAs require no dose adjustments in those with CKD but have limited data in those with severe CKD (eGFR <15 mL/min/1.732 ).13
Until recently, clinical trials with GLP-1 RAs were lacking patient populations selected explicitly for those with CKD or targeting kidney outcomes. Despite this, individual trials and meta-analyses suggested that GLP-1 RAs’ greatest effects on the kidneys were related to decreased albuminuria.21-23 Most recently, the FLOW trial was the first large randomized controlled trial that assessed the effects of a GLP-1 RA on kidney outcomes. The findings demonstrated that semaglutide significantly reduced the risk of major kidney disease and CV events in patients with T2D and CKD.24 Drug discontinuation due to adverse gastrointestinal events was more common in the semaglutide group, but fewer serious adverse events were reported compared to placebo.24
Given the prevalence of CKD in people with diabetes, DCESs are well positioned to assist with regular screening and prompt diagnosis. Evidence of decreased kidney function and structural kidney damage are most often detected through reduced eGFR and elevated UACR. Management should be a comprehensive, holistic approach, including lifestyle and pharmacotherapy interventions. RASi is the backbone of therapy in people with CKD and T2D, and other therapies, such as SGLT2i, ns-MRAs, and GLP-1 RAs, are important additional medications for slowing CKD progression, reducing albuminuria, and providing CV benefit. Making these therapies affordable and accessible to people with diabetes and CKD remains a challenge.
Stacey Cutrell, PharmD, is with High Point University Fred Wilson School of Pharmacy in High Point, NC. Vasyl Zbyrak, PharmD, BCPS, BCACP, is with Temple University School of Pharmacy in Philadelphia, PA. Sarah E. Wheeler, PharmD, BCACP, CDCES, is with Shenandoah University Bernard J. Dunn School of Pharmacy in Winchester, VA. John D. Bucheit, PharmD, BCACP, CDCES, FADCES, and Rachel W. Khan, PharmD, BCPS, are with Virginia Commonwealth University School of Pharmacy in Richmond, VA.
The authors declare having no professional or financial association or interest in an entity, product, or service related to the content or development of this article.
The authors declare having received no specific grant from a funding agency in the public, commercial, or not-for-profit sectors related to the content or development of this article.
Stacey Cutrell https://orcid.org/0009-0005-5788-1130
Sarah E. Wheeler https://orcid.org/0000-0002-6547-8860
John D. Bucheit https://orcid.org/0000-0003-3396-2612
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