Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis.

BACKGRUOUND: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. METHODS: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. RESULTS: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. CONCLUSION: Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Impact of SGLT2 inhibitors on patient outcomes: a network meta-analysis.

BACKGROUND: A comprehensive network meta-analysis comparing the effects of individual sodium-glucose cotransporter 2 (SGLT2) inhibitors on patients with and without comorbidities including diabetes mellitus (DM), heart failure (HF), and chronic kidney disease (CKD) has not been previously conducted. METHODS: We searched PubMed, Embase, Cochrane, and ClinicalTrials.gov for randomized controlled trials up to March 28, 2023. Network meta-analysis using a random-effects model was conducted to calculate risk ratios (RRs). Risk of Bias tool 2.0 was used to assess bias, and CINeMA to assess the certainty of evidence. In the subgroup analysis, the SGLT2 inhibitors were classified into highly (dapagliflozin, empagliflozin, and ertugliflozin) and less selective SGLT2 inhibitors (canagliflozin and sotagliflozin). RESULTS: A total of fourteen trials with 75,334 patients were analyzed. Among these, 40,956 had taken SGLT2 inhibitors and 34,378 had not. One of the main results with particular findings was empagliflozin users had a significantly lower risk of all-cause death compared to dapagliflozin users in DM population (RR: 0.81, 95% CI 0.69-0.96). In HF population, sotagliflozin users had a borderline significantly lower risk of CV death or hospitalization for HF (HHF) than dapagliflozin users (RR: 0.90, 95% CI 0.80-1.01). In non-HF population, those who used canagliflozin had a significantly lower risk of CV death or HHF compared with those who used dapagliflozin (RR: 0.75, 95% CI 0.58-0.98). At last, for HF patients, those who used less selective SGLT2 inhibitors had a significantly lower risk of MACEs compared to those who used highly selective SGLT2 inhibitors (RR: 0.75, 95% CI 0.62-0.90). CONCLUSIONS: Our network meta-analysis revealed that empagliflozin users with diabetes experienced a lower risk of dying from any cause than those using dapagliflozin. Additionally, canagliflozin users demonstrated a reduced risk of cardiovascular death or HHF compared to dapagliflozin users in those without HF. In HF patients, less selective SGLT2 inhibitors showed superior CV composite outcomes, even surpassing the performance of highly selective SGLT2 inhibitors. TRIAL REGISTRATION: PROSPERO [CRD42022361906].

A difficult-to-treat pleuropulmonary histoplasmosis in a patient with rheumatoid arthritis in Taiwan.

Amphotericin B and itraconazole are the primary agents for treating histoplasmosis. Newer azoles are alternatives for patients refractory to or intolerant of standard therapy. We report an 83-year-old woman with rheumatoid arthritis complicated with pleuropulmonary histoplasmosis who responded to liposomal amphotericin B, but progressed under voriconazole and posaconazole maintenance therapy.