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Paul Chadwick

MD Curative Wound Care Consultancy; Visiting Professor Birmingham City University;Associate Editor, the Diabetic Foot Journal

Zibotentan, a developmental endothelin A receptor antagonist, in combination with dapagliflozin in SGLT2 inhibitor-naïve patients, was effective in reducing albuminuria in people with chronic kidney disease (CKD) already on optimised RAAS blockade in the XENITH-CKD trial published in the Lancet. In this randomised, active-controlled, phase 2b clinical trial, adults with CKD, an eGFR of ≥20 mL/min/1.73 m2 and a uACR of 150–5000 mg/g (approximately 17–565 mg/mmol) were randomised to 12 weeks of treatment with zibotentan 1.5 mg daily (high dose; N=179), zibotentan 0.25 mg (low dose; N=91) or placebo (N=177), all in combination with dapagliflozin 10 mg daily, and in addition to full doses of an ACE inhibitor or ARB if tolerated. At 12 weeks, compared with placebo, there was a significant 33.7% reduction in uACR in the high-dose zibotentan group and a 27% reduction in the low-dose group. Fluid retention had been identified in previous studies of endothelin A antagonists; therefore, weight and B-type natriuretic peptide were monitored during the study and demonstrated fluid retention event rates of 18% with high-dose zibotentan and dapagliflozin, 9% with low-dose zibotentan and dapagliflozin, and 8% with dapagliflozin alone.

Pam Brown GP in Swansea

Citation:

Brown P (2023) Diabetes

Distilled: Reaching a XENITH in cardiorenal protection. Diabetes & Primary Care 25: 199–200

Compared to people newly diagnosed with type 2 diabetes who were well controlled on glucoselowering therapy, those who were not on glucose-lowering therapy were found to have a higher 5-year risk of a first major adverse cardiovascular event (MACE), even if they achieved initial diabetes remission using lifestyle changes, according to this Danish real-world cohort study published in Diabetologia. Lower use of statins and RAAS inhibitors for primary prevention were identified in those not on glucose-lowering drugs but with persisting type 2 diabetes or in remission, and this was hypothesised to contribute to the higher MACE rates. Equalising statin and RAAS inhibitor prescribing to levels achieved in people with well-controlled type 2 diabetes taking glucose-lowering drugs was predicted to result in absolute reductions in first MACE risk. Those with poorly controlled type 2 diabetes taking glucose-lowering drug therapy had a similar standardised absolute 5-year cardiovascular risk to those with persisting type 2 diabetes not on glucose-lowering therapy, despite receiving similar levels of statins and RAAS blockade as the well-controlled group. These findings remind us that people newly diagnosed with type 2 diabetes may already be at significant risk of MACE, and we need to consider the need for statins and RAAS inhibitors to reduce this risk, even if glycaemia can be controlled without medication.

Pam Brown

GP in Swansea

Citation: Brown P (2023) Diabetes Distilled: MACE risk higher in newly diagnosed type 2 diabetes treated with lifestyle alone. Diabetes & Primary Care 25: 201–3