Relaxed prescription requirements for add-on sodium-glucose cotransporter 2 inhibitors (SGLT2i) now allow earlier use of these cardiorenal-protective therapies in eligible patients as the second antidiabetic medication after metformin. Dr Paul Lee and Dr David Lui, Specialists in Endocrinology, Diabetes & Metabolism in Hong Kong, discussed how changes in SGLT2i prescription requirements may benefit patients with type 2 diabetes (T2D) who have chronic kidney disease (CKD) or established cardiovascular disease (CVD), and the role of SGLT2i (eg, empagliflozin) in cardiovascular-kidney-metabolic (CKM) syndrome management.
From glucose- to CKM-centred care
Diabetes now affects roughly one in nine people in Hong Kong. [PLoS Med 2026;23:e1004749]
“The major burden of diabetes stems from macrovascular and microvascular complications including CVD and CKD, which is of growing clinical importance,” said Lee.
Recognizing the close interconnections among metabolic dysfunction as well as the cardiovascular (CV) system and the kidneys, the American Heart Association (AHA) Presidential Advisory formally proposed the concept of CKM syndrome to drive improvements in CKM health and related outcomes. This framework uses a five-stage system (stages 0–4) to guide early screening, and risk-stratify individuals according to adverse outcomes associated with more advanced CKM stages. (Figure) [Circulation 2023;148:1606-1635]
“In addition to lifestyle modification and risk factor control, we now have medications that not only independently control glycaemic levels, but also provide cardiorenal benefits,” highlighted Lui and Lee. “As a result, the focus has shifted beyond glycaemic management alone to proactive organ protection.”
Relaxed SGLT2i prescription requirements
“The relaxation in the required number of background antidiabetic medications from two to one for SGLT2i prescription in eligible patients would facilitate cardio-kidney protection for patients with T2D who have established CVD or CKD,” said Lee.
This update closely aligns with the 2026 CKM syndrome guideline jointly issued by the AHA, American College of Cardiology (ACC), American Diabetes Association (ADA), and American Society of Nephrology (ASN), which recommends SGLT2i as guideline-directed medical therapy (GDMT) in patients with T2D at increased CV risk or with atherosclerotic CVD (ASCVD) and those with T2D and CKD. (Table) [Circulation 2026;154:e50-e158] These recommendations are consistent with the ADA, ACC, and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. [Diabetes Care 2025;49:S183-S215; J Am Coll Cardiol 2020;76:1117-1145; Kidney Int 2024;105:S117-S314]
“Both SGLT2i and glucagon-like peptide-1 [GLP-1]–based therapies are cardiorenal-protective agents. Therefore, SGLT2i should be recommended in patients with both CKD and ASCVD,” advised Lui.
CKM benefits of SGLT2i
The CKM benefits of SGLT2i were evaluated in SMART-C, a collaborative meta-analysis involving 72,970 patients with diabetes and established ASCVD or at high risk of ASCVD, heart failure, or CKD across 12 large, randomized, double-blind, placebo-controlled SGLT2i trials. Of these patients, 3,065 (4 percent) were receiving GLP-1 receptor agonists (GLP-1 RAs) at baseline. The trials included in the meta-analysis were EMPA-REG OUTCOME, EMPA-KIDNEY, EMPEROR-Reduced, EMPEROR-Preserved, DECLARE-TIMI 58, DAPA-HF, DELIVER, DAPA-CKD, the CANVAS Programme, CREDENCE, VERTIS-CV, and SCORED. [Lancet Diabetes Endocrinol 2024;12:545-557]
The results showed that use of SGLT2i reduced the risk of major adverse CV events (MACE) both in patients receiving and in those not receiving concomitant GLP-1 RAs (hazard ratio [HR], 0.81; 95 percent confidence interval [CI], 0.63–1.03 and HR, 0.90; 95 percent CI, 0.86–0.94, respectively; pheterogeneity=0.31).
Effects on hospitalization for heart failure or CV death (HR, 0.76; 95 percent CI, 0.57–1.01 and HR, 0.78; 95 percent CI, 0.74–0.82, respectively; pheterogeneity=0.90) and CKD progression (HR, 0.65; 95 percent CI, 0.46–0.94 and HR, 0.67; 95 percent CI, 0.62– 0.72, respectively; pheterogeneity=0.81) were also consistent regardless of GLP-1 RA use.
“There is also evidence that SGLT2i reduced all-cause mortality in patients with T2D at high CV risk and prolonged the time to kidney replacement therapy in patients with CKD,” added Lui. [N Engl J Med 2015;373:2117-2128; Clin Kidney J 2023;16:1187-1198]
“SGLT2i improve glycaemia while having a low risk of hypoglycaemia, reduce blood pressure [BP], and have a modest weight-loss effect, which helps address obesity — the root cause of CKM syndrome,” said Lee. [NPJ Metab Health Dis 2025;3:29; Circulation 2023;148:1606-1635]
How can CKM care improve?
Early detection
“It is important not only to identify patients with diabetes early, but also to detect any complications as early as possible, even at asymptomatic stage,” advised Lee and Lui. “This also applies to patients with hypertension, as both diabetes and hypertension are classified as stage 2 of CKM syndrome.” (Figure)
However, albuminuria screening with urine albumin-to-creatinine ratio (uACR) testing is largely underutilized in patients with diabetes or hypertension. This leads to delayed detection of CKD and hinders timely initiation of GDMT. [Diabetes Obes Metab 2025;27:15-33]
“We should adopt a comprehensive CKM approach, with regular monitoring and management of patients’ CKM risk factors, including glycaemic control, BP, lipid profile, body mass index [BMI], waist circumference, estimated glomerular filtration rate [eGFR] and uACR,” shared Lui. “The frequency of each test is determined by the patients’ stage of CKM syndrome, with more frequent testing for those at more advanced stages.”
Regular screening for complications through assessment of CV risk factors, eGFR and uACR is available for patients with hypertension and diabetes under the Risk Assessment and Management Programme for Hypertension (RAMP-HT) and RAMP for Diabetes Mellitus (RAMP-DM). [Hong Kong Med J 2025;31:58-64]
SGLT2i use and counselling tips
Despite clear guideline recommendations and the significant burden of cardiorenal complications on Hong Kong’s healthcare system, there remains room for SGLT2i to be better utilized in patients with T2D and ASCVD or CKD. [BMC Prim Care 2022;23:317] “Possible clinician-relevant barriers include clinical inertia, cost, consultation time constraints, concerns about adverse effects [AEs], and limited familiarity with SGLT2i,” shared Lui. “From the patients’ perspectives, pill burden, perceived value of treatment, and medication cost are some of the main barriers.”
“Relaxed prescription requirements for SGLT2i may partially alleviate cost concerns and encourage clinicians to recognize the growing evidence supporting SGLT2i use in patients with CKM syndrome,” Lui commented. “After a decade of clinical experience with SGLT2i, we have gained familiarity with this drug class and have become adept at patient counselling.”
“Awareness of the CKM concept is important because patients with well-controlled glycaemia may question the need for additional medications, particularly when some may still perceive SGLT2i as antidiabetic agents,” emphasized Lui. “Reframing SGLT2i as organ-protective medications may improve patients’ acceptance.”
“In patients with detected albuminuria, it is important to clearly explain that albuminuria is a robust prognostic marker for both CV and kidney adverse outcomes, and that SGLT2i are clearly beneficial in this setting,” Lui and Lee emphasized. “This applies to patients with T2D and those with hypertension or obesity. If these patients have comorbid CKD, they will benefit from SGLT2i’s effect of delaying progressive decline in eGFR.”
“During patient counselling before SGLT2i initiation, we should always discuss the anticipated AEs such as urogenital infections, and rare AEs such as diabetic ketoacidosis [DKA],” Lui shared. “By describing the nature of these AEs and emphasizing precautionary strategies, we can promote greater acceptance and adherence.”
HKCP’s position statement
The Hong Kong College of Physicians’ (HKCP) 2025 position statement supports incorporation of the CKM framework into the local healthcare system, to prioritize identifying and treating CKM syndrome. Conditions such as hyperglycaemia, dyslipidaemia, obesity, kidney insufficiency, and hypertension should be viewed as chronic conditions requiring early intervention rather than “risk factors”. [Hong Kong Med J 2025;31:58-64]
Notably, the position statement emphasizes the need for an interdisciplinary care model in Hong Kong, integrating primary care and specialist care (eg, cardiologists, nephrologists, hepatologists, and diabetologists) to prevent complications and protect organs.
Summary
The concept of CKM syndrome emphasizes interconnectedness of metabolic, CV and CKD as well as a holistic framework for interdisciplinary care. Regular screening for complications through assessment of CV risk factors, uACR, and eGFR is essential for patients with T2D, hypertension, or CKD, as they are already at stage 2 of CKM syndrome. [Hong Kong Med J 2025;31:58-64; Circulation 2026;154:e50-e158]
“In addition to lifestyle modification, SGLT2i, as part of GDMT, confer CKM benefits,” said Lee. “HKCP’s position statement, the 2026 AHA/ACC/ADA/ ASN guideline, and relaxed prescription requirements for SGLT2i should increase clinicians’ confidence in advocating early screening, staging, and management of CKM syndrome.”
This special report is supported by an education grant from the industry.
