There is now enough evidence of ‘extra‐glycaemic’ benefits of SGLT-2 inhibitors on cardiovascular and renal function to justify them being used irrespective of glycaemic control, Australian experts say.
The presence of comorbidities such as atherosclerotic cardiovascular disease, heart failure and chronic kidney disease (CKD) should guide the use of SGLT2 inhibitors rather than HbA1c levels or glucose response, according to clinicians in the Department of Endocrinology and Metabolism at St Vincent’s Hospital, Sydney.
In a letter to the Internal Medicine Journal they note that results from landmark trials have shown that the cardiovascular and renal beneﬁts of SGLT2 inhibitors are very likely independent of baseline glycaemia and the glucose-lowering effects of the drugs.
They cite the example of the DAPA-HF trial, in which patients with symptomatic heart failure with reduced ejection fraction randomised to dapagliﬂozin had a signiﬁcantly lower risk of worsening heart failure or cardiovascular death compared to placebo, irrespective of the presence of diabetes.
And similarly the CREDENCE trial showed that patients with type 2 diabetes and nephropathy had a signiﬁcant reduction in end-stage kidney disease when treated with canagliﬂozin compared to placebo despite a minimal difference in HbA1c.
Cardiovascular benefits with SGLT2 inhibitors were also independent of glycaemic effects trials such as EMPA-REG OUTCOME, CANVAS and DECLARE-TIMI 58.
“The discordance between the cardio-renal and glycaemic actions of SGLT2 inhibitors questions the central focus on glycaemic response. There needs to be a broader conceptualisation of response to include the cardiovascular, renal and metabolic effects of these drugs,” say the authors, who include Professor Ric Day and Dr Sophie Stocker.
They note that current PBS criteria for initiating SGLT2 agents in diabetes are based on levels of glycaemia, despite the cardiovascular and renal benefits being unrelated to them. And yet the Australian Diabetes Society algorithm allows SGLT2 inhibitors to be continued for ‘non-glycaemic benefits’ despite a lack of glycaemic response.
“We suggest that consideration be given to initiating SGLT2 inhibitors irrespective of baseline glycaemic control and continuing SGLT2 inhibitors, even in the absence of a significant HbA1c reduction, in light of the extra‐glycaemic benefits of these novel drugs,” they conclude.
The authors did not declare any conflict of interest.