medwireNews: A pooled analysis of the DAPA-HF and DAPA-CKD trials suggests that taking the sodium-glucose cotransporter (SGLT)2 inhibitor dapagliflozin reduced the participants’ risk for developing type 2 diabetes by around a third.
However, in a commentary linked to the study in The Lancet Diabetes & Endocrinology, Alice Cheng (University of Toronto, Ontario, Canada) describes this finding as merely “a bonus.”
She stresses that there are already “sufficiently compelling reasons to use SGLT2 inhibition in patients with chronic kidney disease and heart failure to reduce the risk of both cardiovascular and renal outcomes.”
The analysis by Hiddo Heerspink (University of Groningen, the Netherlands) and colleagues included 1398 people from DAPA-CKD and 2605 from DAPA-HF who did not have type 2 diabetes at baseline.
Around 60% of these people had prediabetes. Cheng says this serves as a reminder “that people with kidney or cardiac disease have a high prevalence of dysglycaemia so we should remember to screen for this.”
Receipt of dapagliflozin did not result in any significant change in glycated hemoglobin levels after 12 months of use, compared with either baseline or placebo. This was the same regardless of whether people had normoglycemia or prediabetes at baseline.
Despite this, a significantly smaller proportion of people taking dapagliflozin than those taking placebo developed diabetes, at 4.3% versus 6.3% (2.6 vs 3.9 events per 100 patient–years), equating to a significant 33% risk reduction.
The difference emerged from 4 months and was driven by diabetes rates in people with prediabetes at baseline (4.2 vs 6.2 events per 100 patient–years); rates in those with baseline normoglycemia were very low (0.3 vs 0.6 events per 100 patient–years).
Cheng observes that this significant effect occurred in the context of no change in glycated hemoglobin and around 30% of people having an estimated glomerular filtration rate below 45 mL/min per 1.73 m2, “a renal threshold below which the glycaemic efficacy of SGLT2 inhibitors is restricted.”
This implies that SGLT2 inhibitor treatment may genuinely prevent type 2 diabetes, rather than just masking its onset, she says, although she adds that “this remains to be proven with a randomised controlled diabetes prevention trial that includes a washout period and tests of insulin sensitivity and β-cell function.”
But Cheng stresses that “although it is intellectually stimulating to consider the why and how of the observed reduction in new onset type 2 diabetes in this pooled analysis, the real message is to use SGLT2 inhibition in this population.”
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Lancet Diabetes Endocrinol 2021; doi:10.1016/S2213-8587(21)00295-3
Lancet Diabetes Endocrinol 2021; doi:10.1016/S2213-8587(21)00310-7