The administrative prevalence of cardiac amyloidosis is approximately 50 per 100 000 person-years. The pathophysiology of amyloidosis involves a misfolding of proteins with a beta-pleated sheet structure. This leads to the deposition of insoluble fibrils in the interstitium, which, in turn, impair organ function and cause a variety of diseases. Systemic types are the most common, especially light-chain (AL) and transthyretin (ATTR) amyloidosis with cardiac involvement. In this article, we present the diagnostic evaluation of amyloidosis and recent developments in its treatment. This review is based on publications retrieved by a selective search in PubMed for registry studies, meta-analyses, randomized controlled trials, systematic reviews, guidelines, and current position papers on "cardiac amyloidosis," "ATTR amyloidosis," "cardiac amyloidosis epidemiology," "cardiac amyloidosis treatment," and "ATTR amyloidosis treatment." Cardiac amyloidosis markedly impairs cardiac function and carries a poor prognosis as well as elevated mortality. The diagnosis is mainly based on specialized imaging studies including echocardiography, cardiac magnetic resonance imaging, and scintigraphy. The goal of treatment is to slow amyloid deposition. In ATTR amyloidosis, transthyretin stabilizers or RNA silencers can stabilize the clinical course: the use of tafamidis has been found to be associated with better outcomes and lower overall mortality at 30 months compared with placebo (HR 0.70 [0.51; 0.96]). Vutrisiran also lowers overall mortality and reduces recurrent cardiovascular events compared to placebo (HR 0.72 [0.56; 0.93]). Cardiac complications and comorbidities can be treated, depending on left ventricular function and drug tolerability, with SGLT2 inhibitors, beta-blockers, and mineralocorticoid receptor antagonists, among other drugs. Advanced cardiac amyloidosis carries a poor prognosis; early diagnosis and targeted treatment are of decisive importance. Better outcomes are now possible with the aid of improved imaging methods, disease-modifying treatment options, and the treatment of cardiac complications. Further approaches are now being studied.

SGLT2i combined with physical training attenuates metabolic dysfunction and pyroptosis-mediated renal cell death in diabetic kidney disease.

Insulin resistance and related metabolic disorders are becoming increasingly common among women of reproductive age. However, the mechanisms by which insulin signaling influences female fertility remain only partially understood. Currently, there is rapid growth in the use of new insulin-sensitizing medications, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, prescribed to women who may want to conceive, raising concerns about reproductive safety and benefits. Insulin acts at multiple points along the hypothalamic-pituitary-gonadal axis, including ovulatory function, oocyte maturation, and endometrial receptivity. Conditions such as polycystic ovary syndrome, diabetes, or obesity may impair oocyte development, modify IVF success rates, and compromise embryo implantation. Emerging evidence suggests that both SGLT2 inhibitors and GLP-1 receptor agonists improve factors such as ovulatory function and androgen balance, though both carry safety concerns during the periconception period. Clinicians managing women of reproductive age with insulin-related metabolic disorders should incorporate reproductive counseling into treatment planning. Ultimately, fertility-focused trials of newer insulin modifiers may be beneficial.

Effects of SGLT2I Therapy on Tubular Reabsorption and Tubular Epithelial Stress Injury in Patients With CKD.

Association of SGLT2 inhibitors with suicidality, all-cause mortality, and hospitalization in bipolar disorder: A cohort study of 1.23 million adults.

SGLT2i-Triggered hyperglycosuria Unveils CDKN2A-Driven distal tubular senescence and EMT, Fueling renal fibrosis.

Heart failure prevalence and incidence in Germany: National data on medical therapy and comorbidities.

Effects of SGLT2 inhibitor dapagliflozin on the heart of rats with long-standing Type 1 diabetes mellitus: Protein profile

Adult-onset seizure reflects the burden of acquired brain insults, but established disease-modifying preventive strategies are limited. We evaluated whether semaglutide initiation is associated with a lower incidence of adult-onset seizure compared with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and other glucose-lowering drugs (GLDs) in adults with type 2 diabetes. Using the All of Us Research Program, we emulated a population-based target trial in new-user, active-comparator cohorts from January 2018 to October 2023. We compared semaglutide vs other GLDs and semaglutide vs SGLT2i. Incident epilepsy or seizure was identified from diagnostic codes. Effects were estimated using inverse probability of treatment weighting with weighted Cox models and targeted maximum likelihood estimation (TMLE). Subgroup and sensitivity analyses with multiple outcome definitions and analytic approaches were conducted to assess the robustness of findings. We evaluated mediation through hemoglobin A1c (HbA1c) and body mass index (BMI) using the longitudinal Vansteelandt framework. We analyzed 10,213 patients in the semaglutide (n = 2,586, mean age, 60.1 years; 56.8% female) vs other GLDs cohort (n = 7,627, mean age, 63.7 years; 54.2% female) and 8,605 patients in the semaglutide (n = 2,814, mean age, 60.5 years; 66.2% female) vs SGLT2i cohort (n = 5,791, mean age, 64.4 years; 47.3% female). Semaglutide was associated with a lower risk of adult-onset seizure compared with other GLDs (weighted HR 0.44 [95% CI 0.25-0.79]; 4-year risk difference -1.78% [95% CI -2.58 to -0.98]) and SGLT2i (weighted HR 0.48 [95% CI 0.27-0.85]; 4-year risk difference -1.46% [95% CI -2.41 to -0.51]). TMLE estimated risk differences per 1,000 persons of -14.20 (95% CI -18.33 to -10.07) vs other GLDs and -7.62 (95% CI -11.65 to -3.60) vs SGLT2i, corresponding to numbers needed to treat of 70 and 131, respectively. Mediation was minimal for HbA1c (2.4% vs other GLDs; 6.5% vs SGLT2i) and BMI (0% vs other GLDs; 0.7% vs SGLT2i). Semaglutide initiation was associated with a lower risk of adult-onset seizure compared with SGLT2i and other GLDs in patients with type 2 diabetes, independent of glycemic and weight effects. Residual confounding, low event counts, and shorter follow-up limit causal interpretation. This study provides Class II evidence that semaglutide use was associated with a lower risk of adult-onset seizures compared with other GLDs and SGLT2i.

Asia faces a rising cancer burden, with type 2 diabetes mellitus (T2DM) prevalence in cancer patients at 24.4% (2.3-fold higher than that of the general population). Antineoplastic therapies (e.g., anthracyclines and vascular endothelial growth factor receptor [VEGFR] inhibitors) increase cardiorenal toxicity, exacerbated by T2DM. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefit non-oncologic populations but are understudied in T2DM-cancer patients. We assessed SGLT2i's effects on antineoplastic-related cardiorenal toxicity/survival via a multicenter retrospective cohort of 248 T2DM-cancer patients (56.0% male, mean age 66.7 years) 1:1 divided into SGLT2i/non-SGLT2i groups. Over 30.4 months of follow-up, SGLT2i reduced cardiovascular events by 86.1% (odds ratio [OR] = 0.139, 95% CI 0.027-0.710, p = .018) and all-cause mortality by 84.7% (HR = 0.153, 95% CI 0.055-0.431, p < .001). Echocardiography showed improved left ventricular ejection fraction (LVEF) and reduced left ventricular end-diastolic diameter (LVID)/left atrial (LA) dimensions (all p < .001). Despite lower baseline estimated glomerular filtration rate (eGFR) in the SGLT2i group, SGLT2i preserved renal function (post-treatment eGFR: 99.8 vs. 67.5 mL/min/1.73 m2; p = .054) and reduced uric acid (UA) levels by 23.6% (p < .001). Benefits persisted across solid tumor/hematological malignancies and anthracycline-based therapy, targeted antineoplastic therapy or immunotherapy subgroups, with no increase in infection. SGLT2i improve cardiorenal outcomes and survival in T2DM-cancer patients warranting prospective validation.

Pharmacologic treatment is widely used for managing gestational diabetes mellitus (GDM). However, evidence remains limited on the comparative effectiveness and safety across different drug classes for GDM. This study aims to compare the efficacy and safety of pharmacologic treatments for GDM using network meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science up to May 16, 2025 to identify trials evaluating glucose levels and maternal or neonatal complications in GDM patients using any pharmacologic agents, e.g., insulin, biguanides, sulfonylureas, α-glycosidase inhibitors, sodium-glucose cotransporter-2(SGLT-2) inhibitors, dipeptidyl peptidase IV(DPP-IV) inhibitors or Glucagon-like peptide-1receptor (GLP-1 RAs) versus standard care. We used random-effects model for both pairwise meta-analyses and frequentist network meta-analyses and applied the Confidence in Network Meta-Analysis (CINeMA) framework to assess the certainty of evidence. Seventy-three articles were eligible, comprising 71 trials in which 14 877 participants were enrolled and seven drug classes assessed. All subsequent effects refer to comparisons with standard care. Because of their moderate to high evidence of certainty, sulfonylureas were established as the most effective drugs used for lowering fasting glucose (mean difference [MD]: -0.33 mmol/L; 95% confidence interval [CI]: -0.55 to -0.1), followed by insulin (MD: -0.3 mmol/L; 95% CI: -0.4 to -0.21) and biguanides (MD: -0.2 mmol/L; 95% CI: -0.28 to -0.12). Biguanides were the most effective drugs used to control haemoglobin A1c (MD: -0.1%; 95% CI: -0.16 to -0.03), but their use was associated with increased adverse events leading to low birth weight among infants (OR: 2.04; 95% CI: 1.04-4.01). Insulin (OR: 0.51; 95% CI: 0.34-0.75), biguanides (OR: 0.39; 95% CI: 0.26-0.59), and sulfonylureas (OR: 0.5; 95% CI: 0.31-0.79) use could decrease the risk of macrosomia. Sulfonylureas were found to be more easily get premature delivery and neonatal hypoglycaemia than biguanides; evidence regarding their impact on low birth weight and long-term safety remains lacking. Insulin use provides significant benefits in achieving glycaemic control and minimising maternal and foetal complications, and it has a favourable overall safety profile. Biguanide use may be associated with an increased risk of low birth weight, warranting careful consideration and thorough counselling for shared decision-making. Currently, insufficient evidence supporting the efficacy and safety of sulfonylureas, α-glycosidase, DPP-IV, and SGLT-2 inhibitors; and GLP-1 RAs in GDM management is available.

Comprehensive drug safety assessment of sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and dipeptidyl peptidase 4 inhibitors: A Danish population-based active comparator new user cohort study.

Patients with type 2 diabetes mellitus (T2DM) are at increased risk of post-acute sequelae after COVID-19 (PASC). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and metformin may have systemic benefits beyond glycemic control. We evaluated the impact of prior SGLT2i and metformin use on the risk of post-acute COVID-19 complications. We conducted a retrospective, population-based cohort study using national healthcare claims databases, from July 1, 2021 to February 28, 2023. Cohorts were stratified based on SGLT2i or metformin, against patients had not received these medications. Overlap weighting was applied to adjust for baseline differences in demographics, vaccination status, comorbidities, and prior healthcare utilization. Competing-risks regression models were used to assess differences in the risk of long-COVID outcomes between 31 and 300days post-infection. Among 71,698 patients with T2DM, 22,501 (31.4%) had prior SGLT2i use, and 66,792 (93.1%) had prior metformin use. Compared with non-SGLT2i users, patients treated withSGLT2i had a significantly lower risk of neurological sequelae (aHR = 0.60 [0.45-0.81]), particularly memory and cognitive impairment (aHR = 0.63 [0.41-0.98]). SGLT2i was also associated with a reduced risk of post-acute symptoms (aHR = 0.87 [0.77-0.99]). Metformin use was associated with significantly lower risk of composite post-acute outcomes (aHR = 0.80 [0.68-0.96]) and post-acute symptoms (aHR = 0.77 [0.63-0.93]). Amongst patients on metformin, the addition of SGLT2i further lowered the risk of neurological sequelae (aHR = 0.81 [0.71-0.93]) and composite symptoms (aHR 0.87 [0.76-0.99]). SGLT2i and metformin use were associated with a lower risk of PASC and post-acute symptoms. There may be additional protective benefits when both agents are used concurrently.

Heart failure (HF) is the leading cause of morbidity and mortality in adults with congenital heart disease (ACHD), yet evidence-based pharmacological options remain limited. Sodium-glucose cotransporter 2 inhibitors (SGLT2I) have demonstrated robust benefits across the heart failure spectrum in acquired cardiovascular disease. This review is summarizing emerging data on the use of SGLT2I in ACHD, a population characterized by unique pathophysiology and unmet therapeutic needs. Recent literature, predominantly comprising case reports, retrospective cohorts, and small prospective studies, suggests that SGLT2I are generally safe and well tolerated in adult congenital heart disease heart failure (ACHD-HF). Across heterogeneous ACHD populations, including those with a systemic right ventricle (SRV) and Fontan circulation, SGLT2I use has been associated with improvements in natriuretic peptides, functional status, exercise capacity, and reductions in HF hospitalizations. Early data support favourable safety and low discontinuation rates. The use of SGLT2I in ACHD-HF is feasible, well tolerated and with potential clinical benefit. Further ACHD-specific randomized clinical trials to define efficacy, optimal patient selection, and long-term outcomes are warranted.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated efficacy and safety in patients with type 2 diabetes mellitus, chronic kidney disease, and heart failure. However, their effects in heart transplant recipients, a population with high cardiovascular risk, remain poorly understood. Clinical trials and observational studies were included. A systematic search was conducted in PubMed, Scopus, EMBASE, and Web of Science. Mean differences (MD) were calculated for continuous outcomes and risk ratios (RR) for binary outcomes, both with 95% confidence intervals (CI). Analyses were performed using RevMan version 5.4.1. Five retrospective cohort studies including 1512 heart transplant recipients (312 SGLT2i users and 1200 controls) were analyzed. SGLT2i use was not associated with significant changes in renal function (MD in eGFR: 3.96 mL/min/1.73 m2; 95% CI: -2.33 to 10.26; p = 0.22) or glycemic control (MD in HbA1c: -0.20%; 95% CI: -0.73 to 0.34; p = 0.47). Mortality was comparable between groups (RR: 0.64; 95% CI: 0.29-1.40; p = 0.26), with no significant increase in urinary tract infections (RR: 1.40; 95% CI: 0.25-7.72; p = 0.70). However, SGLT2i use was associated with significant reductions in body mass index (MD: -0.90 kg/m2; 95% CI: -1.67 to -0.14; p = 0.02) and systolic blood pressure (MD: -4.69 mmHg; 95% CI: -7.27 to -2.12; p < 0.001). In heart transplant recipients, the use of SGLT2 inhibitors was not associated with significant improvements in renal function or glycemic control and did not increase mortality or the incidence of urinary tract infections. However, SGLT2 inhibitor therapy was associated with significant reductions in body mass index and systolic blood pressure, suggesting a potential cardiometabolic benefit in this high-risk population. Given that hypertension and obesity are well-established cardiovascular risk factors and that hypertension, in particular, is a common complication among heart transplant recipients, these blood pressure and weight-lowering effects may be clinically meaningful. PROSPERO CRD420251057335.

Glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter-2 inhibitors in adults with type 2 diabetes and atrial fibrillation: a multicenter comparative effectiveness cohort study of cardiovascular and arrhythmic outcomes.

To investigate the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on cardiovascular function and hepatic metabolism in patients with type 2 diabetes mellitus (T2DM) and metabolic-dysfunction associated steatotic liver disease (MASLD). This is an unblinded real-world study using propensity score analysis of consecutive patients with T2DM and MASLD received either SGLT-2i (dapagliflozin; n = 21), GLP-1RA (dulaglutide; n = 21), or dipeptidyl peptidase-4 inhibitors (DPP-4i; n = 20). At baseline and after 12 months, we assessed the perfused boundary region (PBR) as a marker of glycocalyx thickness, peripheral and central systolic blood pressure (cSBP), pulse wave velocity (PWV), coronary flow reserve (CFR), left ventricular global longitudinal strain (GLS), controlled attenuation parameter (CAP), and liver stiffness (E). At 12 months, all patients had reduced glycosylated hemoglobin and body mass index compared to baseline (P < 0.001), as well as a significant reduction in cSBP, PBR, PWV, CAP, E, and increase in CFR and GLS (P < 0.01). The percentage decrease in peripheral and central SBP was related with the improvement in PBR, PWV, CFR, and GLS at 12 months (P < 0.01). Dulaglutide showed greater improvement in GLS (22.6% vs. 8.5%, vs. 5.9%, P = 0.015) and PBR (P = 0.037) than dapagliflozin and DDP-4i. Both dulaglutide and dapagliflozin showed a greater increase in CFR than DDP-4i post-treatment. The percentage reduction in CAP was associated with the decrease in PBR, PWV and with the increase in GLS (P < 0.05). Twelve-month treatment with either SGLT-2i or GLP-1RA improves central hemodynamics, coronary flow and reduces hepatic steatosis in T2DM individuals with MASLD.

The use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the perioperative setting may lead to SGLT2i-associated postoperative ketoacidosis (SAPKA) in patients with type 2 diabetes (T2D). Therefore, cessation of this drug is recommended before surgery. We aimed to study reported cases to assess the causality of SGLT2i, identify common characteristics, potential risk factors, treatment and outcomes of SAPKA. We conducted a systematic literature search to identify case reports of patients with metabolic acidosis and the presence of ketones who used SGLT2i in the perioperative setting. Case reports were summarised for common characteristics, assessed for quality and distributed to a panel of diabetes experts, who evaluated the likelihood of SAPKA using a questionnaire. Ninety-three papers containing 128 case reports fulfilled the inclusion criteria. The expert panel found SAPKA to be 'likely' in 53 (41%), 'possible' in 38 (30%) and 'unlikely' in 27 (21%) cases; 10 cases (8%) could not be validated due to insufficient data or implausible timing. SAPKA was therefore considered likely or possible in 71% (91/128) of cases. Common factors identified in the SAPKA reports included a diagnosis of T2D mellitus (n = 115), impaired perioperative intake (n = 30) and insufficient insulin supplementation (n = 10). Treatment with insulin was effective, and ketoacidosis resolved in all surviving patients, although significant morbidity, including ICU admission, was reported in a substantial proportion of cases. Confirming a SAPKA diagnosis is challenging due to the variable reporting quality and numerous confounding factors present during the perioperative period. Clinicians should remain aware of SAPKA given the increasing prevalence of SGLT2i use. Focusing on early recognition and treatment represents a potential alternative strategy to routine preoperative SGLT2i discontinuation, though this requires further prospective evaluation. This systematic review presents an overview and discussion of the many, to date, case reports of ketoacidosis thought to be associated with perioperative SGLT2 inhibitor treatment.

The purpose of this study is to investigate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on lower urinary tract symptoms (LUTS) in individuals with type 2 diabetes mellitus (T2DM). While SGLT2i are effective antidiabetic agents with cardiovascular and renal benefits, concerns remain about their impact on LUTS. This prospective observational study included 47 patients with T2DM without organic urinary tract disease or autonomic neuropathy. The Overactive Bladder (OAB)-Validated 8-question (OAB-V8) questionnaire was administered at baseline and reassessed at months 1 and 3 of SGLT2i treatment. The associations of alterations in symptom scores with metabolic parameters were assessed using Spearman's rank correlation. The mean overall OAB-V8 score decreased from 10.1 ± 5.0 to 8.8 ± 6.5 at month 1 (p = 0.01), with no significant difference at month 3 (p = 1.00). Subgroup analyses suggested transient improvement in patients with OAB (n = 17), with scores decreasing from 15.4 ± 4.0 to 12.4 ± 5.7 at month 1 (p = 0.04), followed by a return to baseline at month 3 (16.0 ± 9.0; p = 0.69). Patients without OAB (n = 30) showed stable scores at month 1 (7.1 ± 2.3 to 6.9 ± 6.1; p = 0.24) and dropped significantly by month 3 (6.6 ± 5.4; p = 0.03). Changes in overall scores were independent of body mass index or glycated hemoglobin levels, both in patients with and without OAB. Short-term SGLT2i therapy did not appear to worsen OAB symptoms in patients with T2DM. The results of the subgroup analyses should be viewed cautiously and validated in studies with larger populations. These results provide preliminary reassurance but highlight the need for larger, controlled studies with longer follow-up. The online version contains supplementary material available at 10.1007/s13340-026-00902-9.

Repurposing GLP-1 receptor agonists and SGLT-2 inhibitors in neurodegeneration and metabolically at-risk populations: Myth or reality? An overview of randomized clinical trials.