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Association of British Clinical Diabetologists and UK Kidney Association Joint Clinical Practice Guidelines for the Pharmacological Management of Hyperglycemia in Adults With Type 2 Diabetes Mellitus and CKD

Association of British Clinical Diabetol… · 2025 · United Kingdom

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Authors
Janaka Karalliedde, Kieran McCafferty, Peter Winocour et al.
Title
Association of British Clinical Diabetologists and UK Kidney Association Joint Clinical Practice Guidelines for the Pharmacological Management of Hyperglycemia in Adults With Type 2 Diabetes Mellitus and CKD
Journal
Kidney International Reports, 2025
DOI
10.1016/j.ekir.2025.07.028
Licence
CC BY 4.0
Changes
Verbatim excerpts; formatting adapted

Full text retrieved 2026-10-27 from Europe PMC · PMC12545811

Licence statement of the original publication

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

This page reproduces excerpts of the original publication; the original is authoritative. It has not been reviewed by a physician, does not state a recommendation of Medelix and does not replace medical advice. The guideline may have been updated since.

Open the original publication →Full text on Europe PMC

Recommendations

Verbatim, with grade of recommendation or strength of consensus where given.

Kidney Function Measurements in Determining Medication Dosages in Diabetes

  • We recommend that eGFR is used, preferably using the more accurate serum creatinine–based CKD Epidemiology Collaboration equation, without adjustment for race or ethnicity, when determining if certain therapies can be used to adjust medication dosages in diabetes.16,17 It is important to recognize that eGFR equations have several limitations,18 and hence an individualized pragmatic approach needs to be taken when deciding to initiate or cease medications solely on the basis of kidney function because of these limitations. In the clinical scenarios where creatinine-based eGFR equations may be less reliable (e.g., extremes of body weight) we would recommend using cystatin-based eGFR equations as a more accurate eGFR will better guide or determine treatment adjustments or changes in dosing.

Recommendations

  • Individualized HbA1c targets should be applied in the management of people with CKD, using the levels suggested in Table 1Grade 1B
  • Additional comorbidities, that are frequently seen alongside CKD, and risk of hypoglycemia should influence therapy selection and HbA1c targets. In people who progress to advanced stages of CKD (eGFR < 45 ml/min) or those with rapid progression of CKD, more frequent monitoring of HbA1c and kidney function may be required. (Table 1, Table 2, and Figure 1)Grade 1B
  • Combinations of different classes of drugs are often needed to manage glycemia in CKD; judicious combinations of different classes should be considered based on their benefits and harmsGrade 2D
  • There is no firm evidence that insulin therapy reduces the risk of progressive kidney disease. Therefore, the aim of insulin therapy should be to improve glycemic control and improve quality of life, with a low risk of hypoglycemiaGrade 1C
  • Insulin requirements are likely to rise in the early stages of CKD because of increased insulin resistanceGrade 1C
  • As eGFR declines, insulin requirements are likely to diminish through reduced kidney insulin clearance. In people with CKD stage 3b and below who are on insulin, and whose HbA1c is ≤ 58 mmol/mol (7.5%), reduction of insulin dose should be consideredGrade 1C
  • People with CKD who are treated with insulin should undertake regular glucose monitoringGrade 1C
  • In people who are less able to manage with the requirements of a basal bolus regime, once daily regimes with longer-acting insulins should be consideredGrade 1D
  • If people experience hypoglycemia on neutral protamine Hagedorn (NPH) insulin or premixed insulins, conversion to analogue insulins may be of benefitGrade 1C
  • Metformin can be used down to an eGFR of 30 ml/min per 1.73 m2. The dosage should be reduced to 500 mg twice a day when the eGFR falls below 45 ml/min per 1.73 m2Grade 1B
  • Metformin should be paused during periods of acute illness, particularly when a person has acute kidney injury. Everyone who is treated with metformin should be given sick day guidance, which should be reiterated at every medication reviewGrade 1B
  • In people with eGFR < 60 ml/min per 1.73 m2, metformin should be withheld 24 hours before and up to 48 hours after any procedure that requires the use of radiographic contrast mediaGrade 1B
  • We recommend the consideration of starting SGLT-2 inhibitors in all individuals with T2DM and CKD with an eGFR > 20 ml/min per 1.73 m2Grade 1A
  • Where individuals are already receiving treatment with insulin or sulfonylureas, a reduction in dose of these drugs should be considered in people with T2DM and CKD with eGFR > 45 ml/min per 1.73 m2 and HbA1c that is not very high (e.g., < 64 mmol/mol [8%]) so as to reduce the risk of hypoglycemiaGrade 1A
  • The initiation of SGLT-2 inhibitors in people who have active foot disease (ulceration, infection, sepsis, and ischemia) should be avoided and these agents should be paused in people who develop active infected and/or vascular foot complications while on treatment. SGLT-2 inhibitors should only be reinstated after foot problems have fully resolved and following discussion with the multidisciplinary foot teamexpert opinion, no high-grade evidence
  • SGLT-2 inhibitors should be withdrawn in all people who develop diabetic ketoacidosis. However, if a definitive cause for diabetic ketoacidosis is identified (e.g., low-calorie diet, postoperative catabolic state, and inappropriate cessation of insulin) reinstatement of SGLT-2 inhibitor may be considered depending on careful assessment of the individualized risks and benefits by a diabetes specialistexpert opinion, no high-grade evidence
  • We do not recommend routine assessment of kidney function (creatinine and/or eGFR) within 6 to 8 weeks of SGLT-2 initiation because there is likely to be a transient and physiological deterioration, and this is not a reason to withdraw the drugexpert opinion, no high-grade evidence
  • We recommend that sick day guidance applies, during which SGLT-2 inhibitors should be temporarily paused in scenarios; for example, when people are unable to maintain any oral fluid or food intake for > 24 hours or in settings of acute medical emergencies requiring urgent hospitalization or before major surgery (expert opinion, no high-grade evidence). It is, however, essential that once the acute event has resolved and the person has recovered, the SGLT-2 inhibitor is promptly restarted.
  • We recommend the consideration of the injectable once weekly semaglutide (1 mg/wk subcutaneously) in people with T2DM and albuminuric CKD who have eGFR > 25 ml/min per 1.73 m2, irrespective of glycemic controlGrade 1B
  • Other agents within the class of GLP-1 RA or GLP-1 RA /GIP RA dual agonists can be used for the improvement of glycemic control with a low risk of both hypoglycemia and beneficial effects of weight loss in obese people with T2DM and CKDGrade 1A
  • There is evidence of protection from CVD with some GLP-1 RAs in people who have T2DM and a high risk of CVDGrade 1A
  • People with CKD who are treated with GLP-1 RAs or GLP-1 RA/GIP RA dual agonists need to only perform regular self-monitoring of blood glucose when they are also being treated with drugs that can cause hypoglycemia (sulfonylureas and insulins)Grade 1A
  • We recommend caution for the use of GLP-1 RA or GLP-1 RA/GIP RA dual agonists in people with CKD with advanced active diabetic retinopathy (proliferative diabetic retinopathy) and elevated HbA1c (>86 mmol/mol or 10%) and if treatment is started, avoidance of rapid reduction in HbA1c and liaising with ophthalmology teams to ensure retinal surveillance is in placeexpert opinion no high grade evidence
  • We recommend that people with CKD of all stages are suitable for treatment with DPP-4 inhibitorsGrade 1B
  • We recommend that doses of DPP-4 inhibitors are appropriately reduced in accordance with the degree of kidney impairment (including maintenance hemodialysis) except linagliptinGrade 1B
  • People with CKD can be safely prescribed DPP-4 inhibitors without the risk of hypoglycemia or weight gain at all stages of kidney diseaseGrade 1B
  • There are no current data to suggest that DPP-4 inhibitors (except saxagliptin) are associated with an excess risk of hospitalization for heart failureGrade 1A

Abstract

A growing and significant number of people with diabetes develop chronic kidney disease (CKD), and diabetes-related CKD is a leading cause of end-stage kidney disease (ESKD). People with diabetes and CKD have high morbidity and mortality, predominantly related to cardiovascular disease (CVD).

Hyperglycemia and hypertension are modifiable risk factors to prevent the onset and progression of CKD and related CVD. Recent clinical trials of people with type 2 diabetes mellitus (T2DM) and CKD have demonstrated reduction in composite kidney end point events (significant decline in kidney function, need for kidney replacement therapy, and kidney-related death) and cardiovascular risk with sodium-glucose cotransporter 2 (SGLT-2) inhibitors, nonsteroidal mineralocorticoid receptor antagonists (nsMRAs) and glucagon-like peptide 1 (GLP-1) receptor agonists (RAs).

The Association of British Clinical Diabetologists and UK Kidney Association Diabetic Kidney Disease Clinical Speciality Group have previously undertaken a narrative review and critical appraisal of the available evidence to inform clinical practice guidelines for the pharmacological management of hyperglycemia in adults with T2DM and CKD. This 2025 abbreviated updated guidance by a multidisciplinary group of health care professionals from primary and secondary care settings summarizes the key recommendations, clinical considerations and recent evidence that has implications for clinical practice for health care professionals who treat people with T2DM and CKD.

Contents of the original publication

The section headings of the original.

  • Background
  • Glycemic Targets for the Prevention and Management of CKD in People With Diabetes
  • Glycated Hemoglobin Targets for People who Have T2DM and CKD
  • Kidney Function Measurements in Determining Medication Dosages in Diabetes
  • Glucose-Lowering Therapies for People who Have T2DM and CKD
  • Insulin Therapy in People With CKD
  • Metformin
  • SGLT-2 Inhibitors
  • Practical Aspects of Using SGLT-2 Inhibitors in People With T2DM and CKD
  • GLP-1 RAs and Dual GLP-1 RA and GIP Agonists
  • DPP-4 Inhibitors
  • Sulfonylureas
  • Pioglitazone
  • nsMRAs
  • Cost-Effectiveness of Newer Treatments
  • Conclusion

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