Evaluation of the Lifetime Benefits of Metformin and SGLT2 Inhibitors in Type 2 Diabetes Mellitus Patients with Cardiovascular Disease: A Systematic Review and Two-Stage Meta-Analysis.

BACKGROUND: Metformin and sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular benefits but their comparative effects on mortality in type 2 diabetes mellitus (T2DM) patients with cardiovascular disease (CVD) are unknown. Hence, we evaluated and compared lifetime benefits arising from metformin or SGLT2 inhibitors in T2DM patients with CVD. MATERIALS AND METHODS: Studies published in the PubMed, EMBASE and CENTRAL databases before 28 October 2023 were retrieved. Treatment effects of metformin against US FDA-approved SGLT2 inhibitors in T2DM patients with CVD were evaluated and lifetime gains in event-free survival were estimated from our primary endpoints of all-cause and cardiovascular mortality. Risk ratios were derived to assess their impact on secondary outcomes such as major adverse cardiovascular events and hospitalizations for heart failure. RESULTS: Overall, 14 studies were included. Five studies published Kaplan-Meier curves for the primary outcome of all-cause mortality. Individual participant data were reconstructed from these Kaplan-Meier curves, from which we conducted our two-stage meta-analysis. Participants receiving metformin and SGLT2 inhibitors experienced a reduction in the risk for all-cause mortality as compared with those not taking metformin and placebo. However, participants receiving SGLT2 inhibitors had a higher all-cause mortality (hazard ratio 1.308, 95% confidence interval 1.103-1.550) versus metformin. Treatment with metformin was estimated to offer an additional 23.26 months of survival free from all-cause mortality versus 23.04 months with SGLT2 inhibitors. CONCLUSIONS: In patients with T2DM and CVD, metformin and SGLT2 inhibitors were associated with substantially lower all-cause mortality rates and slightly longer life expectancies than in patients without. Metformin presented an advantage over SGLT2 inhibitors in reducing all-cause mortality.

'Insight' in medical training: what, why, and how?

The term 'insight' is generically defined in English language as the ability to perceive deeper truths about people and situations. In clinical practice, patient insight is known to have important implications in treatment compliance and clinical outcomes, and can be assessed clinically by looking for the presence of illness awareness, correct attribution of symptoms to underlying condition, and acceptance of treatment. In this article, we suggest that cultivating insight is actually a highly important, yet often overlooked, component of medical training, which may explain why some consistently learn well, communicate effectively, and quickly attain clinical competency, while others struggle throughout their clinical training and may even be difficult to remediate. We herein define 'insight' in the context of medical training as having an astute perception of personal cognitive processes, motivations, emotions, and ability (strengths, weaknesses, and limitations) that should drive self-improvement and effective behavioural regulation. We then describe the utility of cultivating 'insight' in medical training through three lenses of (i) promoting self-regulated, lifelong clinical learning, (ii) improving clinical competencies and person-centred care, and (iii) enhancing physician mental health and well-being. In addition, we review educational pedagogies that are helpful to create a medical eco-system that promotes the cultivation of insight among its trainees and practitioners. Finally, we highlight several tell-tale signs of poor insight and discuss psychological and non-psychological interventions that may help those severely lacking in insight to become more amenable to change and remediation.

Left Ventricular Ejection Fraction Association with Acute Ischemic Stroke Outcomes in Patients Undergoing Thrombolysis.

(1) Background: Little is known about how left ventricular systolic dysfunction (LVSD) affects functional and clinical outcomes in acute ischemic stroke (AIS) patients undergoing thrombolysis; (2) Methods: A retrospective observational study conducted between 2006 and 2018 included 937 consecutive AIS patients undergoing thrombolysis. LVSD was defined as left ventricular ejection fraction (LVEF) < 50%. Univariate and multivariate binary logistic regression analysis was performed for demographic characteristics. Ordinal shift regression was used for functional modified Rankin Scale (mRS) outcome at 3 months. Survival analysis of mortality, heart failure (HF) admission, myocardial infarction (MI) and stroke/transient ischemic attack (TIA) was evaluated with a Cox-proportional hazards model; (3) Results: LVSD patients in comparison with LVEF ≥ 50% patients accounted for 190 and 747 patients, respectively. LVSD patients had more comorbidities including diabetes mellitus (100 (52.6%) vs. 280 (37.5%), p < 0.001), atrial fibrillation (69 (36.3%) vs. 212 (28.4%), p = 0.033), ischemic heart disease (130 (68.4%) vs. 145 (19.4%), p < 0.001) and HF (150 (78.9%) vs. 46 (6.2%), p < 0.001). LVSD was associated with worse functional mRS outcomes at 3 months (adjusted OR 1.41, 95% CI 1.03-1.92, p = 0.030). Survival analysis identified LVSD to significantly predict all-cause mortality (adjusted HR [aHR] 3.38, 95% CI 1.74-6.54, p < 0.001), subsequent HF admission (aHR 4.23, 95% CI 2.17-8.26, p < 0.001) and MI (aHR 2.49, 95% CI 1.44-4.32, p = 0.001). LVSD did not predict recurrent stroke/TIA (aHR 1.15, 95% CI 0.77-1.72, p = 0.496); (4) Conclusions: LVSD in AIS patients undergoing thrombolysis was associated with increased all-cause mortality, subsequent HF admission, subsequent MI and poorer functional outcomes, highlighting a need to optimize LVEF.

Percutaneous coronary intervention in patients aged 80 years old and above: a systematic review and meta-analysis.

Background: Ischaemic heart disease remains the main cause of death in the world. With increasing age, frailty and comorbidities, senior patients aged 80 years old and above who undergo percutaneous coronary intervention (PCI) are at higher risk of mortality and other complications. Aims: We aimed to examine the overall outcomes for this group of patients. Methods: Four databases (PUBMED, EMBASE, SCOPUS and CENTRAL) were searched. Studies with patients aged 80 years old and above who underwent PCI for all indications were included. Pooled outcomes of all-cause death, cardiac death, in-hospital death, subsequent stroke/transient ischaemic attack (TIA), subsequent myocardial infarction (MI), subsequent congestive cardiac failure (CCF), and overall major adverse cardiac events (MACE) were obtained for meta-analysis. Results: From 2,566,004 patients, the pooled cumulative incidence of death was 19.22%, cardiac death was 7.78%, in-hospital death was 7.16%, subsequent stroke/TIA was 1.54%, subsequent MI was 3.58%, subsequent CCF was 4.74%, and MACE was 17.51%. The mortality rate of all patients was high when followed up for 3 years (33.27%). ST-elevation myocardial infarction patients had more outcomes of in-hospital death (14.24% vs 4.89%), stroke/TIA (1.93% vs 0.12%), MI (3.68 vs 1.55%) and 1-year mortality (26.16% vs 13.62%), when compared to non-ST-elevation myocardial infarction patients. Conclusions: There was a high mortality rate at 1 year and 3 years post-PCI in the overall population of senior patients aged 80 years old and above, regardless of indication. This necessitates further studies to explore the implications of these observations.