Diabetes association with self-reported health, resource utilization, and prognosis post-myocardial infarction.

BACKGROUND: Diabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health-related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post-myocardial infarction (MI) patients with and without DM. HYPOTHESIS: In post-MI patients, DM is associated with worse HRQoL, increased HRU, and worse clinical outcomes. METHODS: The prospective, observational long-term risk, clinical management, and healthcare Resource utilization of stable coronary artery disease study obtained data from 8968 patients aged ≥50 years 1 to 3 years post-MI (369 centers; 25 countries). Patients with ≥1 of the following risk factors were included: age ≥65 years, history of a second MI >1 year before enrollment, multivessel coronary artery disease, creatinine clearance ≥15 and <60 mL/min, and DM treated with medication. Self-reported health status was assessed at baseline, 1 and 2 years and converted to EQ-5D scores. The main outcome measures were baseline HRQoL and HRU during follow-up. RESULTS: DM at enrollment was 33% (2959 patients, 869 insulin treated). Mean baseline EQ-5D score (0.86 vs 0.82; P < .0001) was higher; mean number of hospitalizations (0.38 vs 0.50, P < .0001) and mean length of stay (LoS; 9.3 vs 11.5; P = .001) were lower in patients without vs with DM. All-cause death and the composite of CV death, MI, and stroke were significantly higher in DM patients, with adjusted 2-year rate ratios of 1.43 (P < .01) and 1.55 (P < .001), respectively. CONCLUSIONS: Stable post-MI patients with DM (especially insulin treated) had poorer EQ-5D scores, higher hospitalization rates and LoS, and worse clinical outcomes vs those without DM. Strategies focusing specifically on this high-risk population should be developed to improve outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01866904 (https://clinicaltrials.gov)

Sodium-glucose co-transporter-2 inhibitors for hospitalised patients with COVID-19: a prospective meta-analysis of randomised trials

BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been proposed as a potential treatment for adults hospitalised with COVID-19, due to their potential anti-inflammatory and endothelial protective effects. Published evidence from randomised control trials (RCTs) does not provide evidence of benefit. We aimed to estimate the effect of oral administration of SGLT2 inhibitors compared with usual care or placebo in adults hospitalised with COVID-19. METHODS: Eligible RCTs that estimated the effect of oral administration of SGLT2 inhibitors compared with usual care or placebo on 28-day all-cause mortality (primary outcome) were included in this prospective meta-analysis. The primary safety outcome was ketoacidosis by 28 days. Trials were identified through systematic searches of ClinicalTrials.gov, EudraCT, and the WHO ISRCTN registry between Nov 1, 2022 and Jan 31, 2023. The search terms were "random*" AND "COVID" AND each SGLT2i, not restricted by trial status or language. Individual searches were then combined. Prespecified summary outcome data, overall and within subgroups of interest, were provided by each trial. The primary analyses were inverse variance weighted meta-analysis of odds ratios (ORs). Risk of bias was assessed using the Cochrane Risk of Bias tool. This study was registered with PROSPERO, CRD42023406442. FINDINGS: Three eligible trials randomly assigned 6096 participants (3025 to the SGLT2 inhibitor group and 3071 to the usual care or placebo group). 2381 (39%) patients were women and 1547 (25%) had type 2 diabetes at randomisation. By 28 days, there were 351 deaths in the SGLT2 inhibitor group and 382 deaths in the usual care or placebo group (summary OR 0·93 [95% CI 0·79-1·08]; p=0·33, I2 for inconsistency across trials 0%). The risk of bias was assessed as being low. Ketoacidosis was observed in seven participants in the SGLT2 inhibitor group and two patients in the usual care or placebo group. INTERPRETATION: Although administration of SGLT2 inhibitor was safe, we found no clear evidence that adding SGLT2 inhibitor therapy improved outcomes in patients hospitalised with COVID-19 compared with usual care or placebo. These data do not support the use of SGLT2 inhibitors as standard treatment in adults hospitalised for COVID-19. FUNDING: None

Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Co-Transporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Cardiovascular Outcomes Trials.

BACKGROUND:Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose contransporter-2 inhibitors (SGLT2i) have emerged as two new classes of antihyperglycemic agents that also reduce cardiovascular risk. The relative benefits in patients with and without established atherosclerotic cardiovascular disease (ASCVD) for different outcomes with these classes of drugs remain undefined. METHODS:We performed a systematic review and trial-level meta-analysis of GLP1-RA and SGLT2i cardiovascular outcomes trials using the PubMed and EMBASE databases. The primary outcomes were: the composite of myocardial infarction, stroke, and cardiovascular death (MACE); hospitalization for heart failure (HHF); and progression of kidney disease. RESULTS:In total, data from 8 trials and 77,242 patients, 42,920 (55.6%) in GLP1-RA trials and 34,322 (44.4%) in SGLT2i trials, were included. Both drug classes reduced MACE in a similar magnitude with GLP1RA reducing the risk by 12% (HR 0.88, 95%-CI 0.84 to 0.94; p<0.001) and SGLT2i by 11% (HR 0.89, 95%-CI 0.83 to 0.96; p=0.001). For both drug classes, this treatment effect was restricted to a 14% reduction in those with established ASCVD (HR 0.86, 95%-CI 0.80 to 0.93, P=0.002) whereas no effect was seen in patients without established ASCVD (HR 1.01, 95%-CI 0.87 to 1.16, P=0.81; p-interaction 0.028). SGLT2i reduced HHF by 31% (HR 0.69, 95%-CI 0.61-0.79, P<0.001) whereas GLP1-RA did not have a significant effect (HR 0.93, 95%-CI 0.83 to 1.04, p=0.20). Both GLP1-RA (HR 0.82, 95%-CI 0.75-0.89, p<0.001) and SGLT2i (HR 0.62, 95%-CI 0.58-0.67, p<0.001) reduced the risk of progression of kidney disease including macroalbuminuria, but only SGLT2i reduced the risk of worsening eGFR, end-stage kidney disease, or renal death (HR 0.55, 95%-CI 0.48-0.64, p<0.001). CONCLUSIONS:In trials reported to date, GLP1-RA and SGLT2i reduce atherosclerotic MACE to a similar degree in patients with established ASCVD, whereas SGLT2i have a more marked effect on preventing HHF and progression of kidney disease. Their distinct clinical benefit profiles should be considered in the decision-making process when treating patients with T2DM

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) for hospitalised patients with COVID-19: prospective meta-analysis of randomised trials

Background Sodium–glucose co-transporter-2 (SGLT2) inhibitors have been proposed as a potential treatment for adults hospitalised with COVID-19, due to their potential anti-inflammatory and endothelial protective effects. Published evidence from randomised control trials (RCTs) does not provide evidence of benefit. We aimed to estimate the effect of oral administration of SGLT2 inhibitors compared with usual care or placebo in adults hospitalised with COVID-19.Methods Eligible RCTs that estimated the effect of oral administration of SGLT2 inhibitors compared with usual care or placebo on 28-day all-cause mortality (primary outcome) were included in this prospective meta-analysis. The primary safety outcome was ketoacidosis by 28 days. Trials were identified through systematic searches of ClinicalTrials.gov, EudraCT, and the WHO ISRCTN registry between Nov 1, 2022 and Jan 31, 2023. The search terms were “random*” AND “COVID” AND each SGLT2i, not restricted by trial status or language. Individual searches were then combined. Prespecified summary outcome data, overall and within subgroups of interest, were provided by each trial. The primary analyses were inverse variance weighted meta-analysis of odds ratios (ORs). Risk of bias was assessed using the Cochrane Risk of Bias tool. This study was registered with PROSPERO, CRD42023406442.Findings Three eligible trials randomly assigned 6096 participants (3025 to the SGLT2 inhibitor group and 3071 to the usual care or placebo group). 2381 (39%) patients were women and 1547 (25%) had type 2 diabetes at randomisation. By 28 days, there were 351 deaths in the SGLT2 inhibitor group and 382 deaths in the usual care or placebo group (summary OR 0·93 [95% CI 0·79–1·08]; p=0·33, I² for inconsistency across trials 0%). The risk of bias was assessed as being low. Ketoacidosis was observed in seven participants in the SGLT2 inhibitor group and two patients in the usual care or placebo group.Interpretation Although administration of SGLT2 inhibitor was safe, we found no clear evidence that adding SGLT2 inhibitor therapy improved outcomes in patients hospitalised with COVID-19 compared with usual care or placebo. These data do not support the use of SGLT2 inhibitors as standard treatment in adults hospitalised for COVID-1