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© ANIMATED HEALTHCARE LTD/SPL. Glucose excretion from kidney following SGLT-2 treatment.
Call for more trials on glucose-lowering agents to treat diabetes and CKD

By Nicole MacKee
Large randomised controlled trials (RCTs) into glucose-lowering agents in people with diabetes and chronic kidney disease (CKD) are ‘urgently needed’, say the authors of a recent Cochrane Review.

The authors evaluated 44 studies involving more than 13,000 people and concluded that the best available evidence for lowering glucose levels supported the use of sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) agonists in people with an estimated glomerular filtration rate of 30 to <60 mL/min.

The Cochrane authors found ‘moderate certainty evidence’ that SGLT-2 inhibitors reduced glucose levels as well as blood pressure, potassium levels and heart failure risk. However, the drugs also increased the risk of genital infections and slightly reduced kidney function in the short term.

GLP-1 agonists ‘probably’ reduced glucose levels and might also reduce weight, the authors reported, but the drugs’ effect on kidney function, hypoglycaemia, gastrointestinal symptoms and pancreatitis was uncertain.

The authors said the benefits and safety of other classes of glucose-lowering drugs were uncertain.

‘The lack of high certainty evidence reviewed, highlights the urgent need for more large-scale RCTs of glucose-lowering agents in people with both diabetes and CKD,’ the authors wrote.

Lead author Dr Clement Lo, Consultant Endocrinologist and Research Fellow at Monash Health and Monash University’s School of Public Health and Preventive Medicine, Melbourne, said the key challenges in managing diabetes in patients with CKD were the significant changes that occurred in glucometabolism and renal drug clearance (including renal replacement therapy). ‘These can increase the risk of hyperglycaemia and hypoglycaemia,’ he said.

Dr Lo said the lack of high certainty evidence meant individualisation of treatment was very important.

‘There is a great need for active comparator trials or trials of new agents versus standard care among patients with diabetes and CKD,’ he said. ‘Until this evidence is available, prescribing decisions will have to be guided by evidence and experience from patients without CKD.’

Dr Lo said ‘living systematic reviews’ were also needed and his research group, led by Professor Sophia Zoungas, was already updating the Cochrane Review to include important trials published in the past six months.
Cochrane Database Syst Rev 2018; (9): CD011798.