Impact of dapagliflozin on cardiometabolic outcomes after myocardial infarction according to baseline glycaemic status and body mass index: a DAPA-MI substudy
Authors: Storey R F , Deanfield J , James S , Ajjan R , Eriksson N , Erlinge D , De Belder M , Gale C P , Zaman A , Hofmann R , Jiang Y , Langkilde A M , Parvaresh Rizi E , Oldgren J , Mcguire D K 
Published: October 2024

Abstract

Background
Dapagliflozin improved cardiometabolic outcomes compared with placebo following acute myocardial infarction (MI) in participants without prior diabetes mellitus (DM) or chronic heart failure (HF) in the DAPA-MI trial.

Purpose
To assess cardiometabolic outcomes in the DAPA-MI trial according to glycaemic status and body mass index (BMI) at randomisation (baseline).

Methods
Participants were categorised, according to their baseline HbA1c, as normoglycaemic (&lt;5.7% [39 mmol/mol]) or having pre-DM (5.7-&lt;6.5% [48 mmol/mol]). Those with HbA1c &gt;6.5%, diagnosis of DM during hospitalisation, or missing HbA1c result were excluded. New-onset DM during follow-up was defined as either investigator-reported DM diagnosis or HbA1c &gt;6.5%. Time to first occurrence of new-onset DM was assessed according to randomised treatment with dapagliflozin or placebo over median 11.6 months. Incidences of hospitalisation for HF (HHF), cardiovascular death/MI/stroke (MACE), first occurrence of NYHA class III or IV, and weight reduction &gt;5% were assessed according to baseline HbA1c subgroup. Hazard ratios with 95% confidence intervals (CI) were determined using Cox proportional hazards models, stratified by country (UK and Sweden), including randomized treatment as covariate. Similar analyses were performed according to baseline BMI ranges &lt;25, &gt;25-&lt;30, and &gt;30 kg/m2.

Results
3,425 out of 4,017 (85.3%) participants met the inclusion criteria, of whom 1,926 (56.2%) were normoglycemic and 1,499 (43.8%) had pre-DM at baseline. In those with normoglycaemia, new-onset DM during follow-up occurred in 6 (0.6%) and 15 (1.6%) participants assigned to dapagliflozin and placebo, respectively (HR 0.40, CI 0.15-1.03; P=0.06); in those with pre-DM, this outcome occurred in 77 (10.1%) and 97 (13.1%) participants, respectively (HR 0.74, CI 0.55-0.99; P&lt;0.05), without significant interaction between the subgroups (P int=0.23)(Figure). A similar pattern was seen for new-onset DM during follow-up according to the BMI subgroup (P int=0.22), with greater absolute risk reduction seen in patients with obesity (5.0% vs. 9.8%, HR 0.52, 0.32-0.82; P&lt;0.01)(Figure). There was no significant treatment effect or interaction according to baseline HbA1c for incidences of HHF or MACE, whereas first occurrence of NYHA class III or IV was reduced more with dapagliflozin versus placebo in the pre-DM subgroup (HR 0.38, CI 0.23-0.61; P&lt;0.001) compared with the normoglycaemia subgroup (HR 0.87, CI 0.58-1.30; P=0.50; P int&lt;0.01). Dapagliflozin increased the incidence of &gt;5% weight loss in both HbA1c subgroups and all BMI subgroups with no significant interactions.

Conclusions
Dapagliflozin, compared with placebo, reduces the occurrence of new-onset DM following MI, regardless of baseline HbA1c or BMI and with greater absolute risk reduction in those with pre-DM or obesity. Dapagliflozin has a greater beneficial effect on HF symptom burden (NYHA class III-IV) in those with pre-DM versus normoglycaemia.