Introduction Type 2 diabetes mellitus (T2DM) often requires combination therapy when metformin alone fails to achieve adequate glycemic control. Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, and glimepiride, a sulfonylurea, are commonly prescribed as add-on therapies. This study compared their efficacy and safety in patients with inadequately controlled T2DM. Methods A nonrandomized prospective observational comparative study was conducted at a tertiary care teaching hospital between April and November 2024. A total of 170 adults with inadequately controlled T2DM receiving metformin (1000 mg) were allocated to receive either dapagliflozin (10 mg) (n=85) or glimepiride (2 mg) (n=85) and were followed for 24 weeks. Primary outcomes included changes in glycated hemoglobin (HbA1c), fasting blood sugar (FBS), and postprandial blood sugar (PPBS). Secondary outcomes included body weight, blood pressure, and adverse events. Results Both treatment groups demonstrated significant improvements in glycemic control over 24 weeks. At study completion, HbA1c was significantly lower in the dapagliflozin group than in the glimepiride group (7.60±0.64% vs. 8.00±0.68%; p=0.01). Glimepiride produced a greater reduction in FBS (101.82±20.65 vs. 115.98±15.09 mg/dL; p<0.001), while PPBS was comparable between groups (p=0.45). Dapagliflozin resulted in significant weight loss and reductions in systolic and diastolic blood pressure, whereas glimepiride was associated with weight gain. Overall, adverse events were more frequent with dapagliflozin, primarily polyuria and genital infections, while hypoglycemia and tremors occurred more frequently with glimepiride. Conclusions Both dapagliflozin and glimepiride were effective as add-on therapy to metformin in improving glycemic control. Dapagliflozin was associated with greater HbA1c reduction, weight loss, lower blood pressure, and a lower risk of hypoglycemia, whereas glimepiride achieved greater fasting glucose reduction. Treatment selection should be individualized based on patient characteristics, comorbidities, and therapeutic goals.

This study aimed to elucidate how sodium-glucose cotransporter 2 (SGLT2) inhibitors and sulfonylureas differentially modulate hepatic metabolism in persons with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D). In this 48-week randomized, open-label, parallel-group trial, Japanese participants with type 2 diabetes and biopsy-confirmed MASLD received either tofogliflozin or glimepiride. Paired liver biopsy samples and serum were collected at baseline and after 48 weeks. We performed a post hoc metabolomic analysis to assess hepatic and systemic metabolic shifts and their correlations with histological and clinical parameters. Tofogliflozin treatment significantly increased hepatic glucose 1-phosphate and acetyl-CoA levels, reflecting a metabolic shift toward ketogenesis and gluconeogenesis. Regarding TCA cycle intermediates, tofogliflozin elevated serum citrate but reduced serum succinate; notably, the reduction in succinate correlated with reduction in liver enzyme levels. Furthermore, higher baseline serum succinate predicted superior histological improvements (ballooning and inflammation) in the tofogliflozin group. In contrast, glimepiride specifically reduced hepatic branched-chain amino acids (BCAAs), which was associated with decreased steatosis. Tofogliflozin also elevated serum urea cycle intermediates, suggesting a distinct "aestivation-like" response to hypovolemia. The metabolic signature of SGLT2 inhibitors in the human liver is characterized by starvation-induced glucose production and hypovolemia-induced aestivation-like response. Serum succinate emerged as a potential biomarker associated with MASLD severity and treatment-related improvements under SGLT2 inhibition.

Given that alpinetin possesses hypoglycemic and cardioprotective properties, it holds potential for co-administration with the antidiabetic agent glimepiride. The aim was to evaluate the impact of alpinetin on the pharmacokinetics and hypoglycemic efficacy of glimepiride, thereby providing a foundation for the development of alpinetin and informing its potential clinical translation. Pharmacokinetic studies were performed in rats following oral administration of glimepiride (1 mg/kg) alone or combined with alpinetin (30 mg/kg). The effect of the combination of glimepiride and alpinetin on blood glucose levels was investigated in a rat model of type 2 diabetes mellitus (T2DM). In vitro experiments were conducted to evaluate the effect of alpinetin on glimepiride metabolic stability and to assess its role on cytochrome P450 2C9 (CYP2C9) activity. Co-administration of glimepiride with alpinetin resulted in significant changes in the pharmacokinetics of glimepiride, as evidenced by an increase in area under the concentration-time curve (AUC), elimination half-life (t1/2), maximum concentration (Cmax), and a decrease in clearance. Glimepiride in combination with alpinetin enhanced the hypoglycemic effect in T2DM rats. Mechanistic studies in liver microsomes revealed that alpinetin improved glimepiride metabolic stability and inhibited CYP2C9 activity. The combination of glimepiride with alpinetin may increase the systemic exposure of glimepiride through inhibition of CYP2C9 activity. This likely contributes to the enhanced hypoglycemic effect observed, but also underscores the need for caution regarding the potential risk of hypoglycemia.

Although sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with a lower risk of hypoglycemia, they may result in weight reduction, and provide additional benefits for cardiovascular disease, chronic kidney disease, and heart failure. However, their use in Japanese individuals with type 2 diabetes (T2D)-many of whom are older and without obesity-raises concerns regarding sarcopenia. This study aims to investigate the impact of the SGLT2 inhibitor tofogliflozin, compared with sulfonylurea glimepiride, on skeletal muscle mass in patients with T2D without obesity.

Diabetes mellitus is a chronic metabolic disorder affecting millions worldwide, necessitating the effective management of blood glucose levels through anti-diabetic medications. Sulfonylureas and Biguanides, particularly Gliclazide, Glimepiride, Glipizide, Glibenclamide, and Metformin, are commonly used in combination therapies for improved glycemic control. Several methods, including UV spectrophotometry, high-performance liquid chromatography, high-performance thin-layer chromatography, micellar chromatography, and liquid chromatography-mass spectrometry, were assessed for their effectiveness. This study evaluates various analytical techniques employed to ensure the quality, efficacy, and safety of these formulations, under the ICH guidelines. RP-HPLC emerged as the most reliable technique, demonstrating superior sensitivity, precision, and linearity, with optimized retention times and low detection limits. LC-ESI-MS/MS exhibited the highest sensitivity, precision, and linearity, making it suitable for pharmacokinetic studies. Spectrophotometric and electrochemical methods provided cost-effective alternatives but lacked sensitivity. RP-HPLC and MS-based techniques can enhance data processing efficiency. These advancements will strengthen pharmaceutical quality control, ensure the safety and efficacy of anti-diabetic drug formulations, while optimizing therapeutic outcomes for diabetes management.

Several studies have supported Dr Gideon Koren’s 1993 landmark article, “Medications Which Can Kill a Toddler with One Tablet or Teaspoonful.” Although each study has its own merits, most focus solely on pediatric overdoses, and few provide an exhaustive reference list for real-time evaluation of ingestions in children and adults. The following xenobiotics warrant special attention because of their potential to cause serious outcomes, even after exposure to small volumes. This list does not imply that all pediatric exposures to these agents result in fatality, and the absence of a xenobiotic from this list does not indicate that it is necessarily safe. α1-Adrenergic agonists and imidazoline receptor agonists: Clonidine, guanfacine, naphazoline, oxymetazoline, tetrahydrozoline, xylazine (veterinary). Sulfonylureas: Chlorpropamide, glyburide, glipizide, glimepiride. Calcium channel blockers: Verapamil, diltiazem, nifedipine, amlodipine, nicardipine, nimodipine; β-Blockers: Metoprolol, labetalol, propranolol, sotalol. Tricyclic antidepressants: Imipramine, desipramine, amitriptyline, nortriptyline. Opioids: Codeine, hydrocodone, methadone, morphine, heroin. Antidiarrheals: Diphenoxylate plus atropine, loperamide. Salicylates and methyl salicylate: Oil of wintergreen, bismuth subsalicylate, mentholated balms, paramao or lawang root oil . Antipsychotics: Loxapine, thioridazine, chlorpromazine. Antimalarials: Chloroquine, hydroxychloroquine, quinine, primaquine. Antiarrhythmics: Quinidine, disopyramide, procainamide, flecainide, amiodarone. Camphor: A terpenoid used as an analgesic, antipruritic agent, and component of cooling gels, ointments, balms, mothballs, household fragrances, and essential oils. Oral camphor use occurs in some regions for religious ceremonies, traditional remedies, aphrodisiacs, or lactation suppression. Nonalkaloid toxic lignan: Podophyllin, podofilox. Unique plant toxins: Colchicine. Oral acetylcholinesterase inhibitors: Rivastigmine, donepezil, galantamine, carbamate pesticides. Methylxanthines: Theophylline, 1,3-dimethylxanthine, caffeine. Other opioids: Buprenorphine, fentanyl. Toxic alcohols: Methanol, ethylene glycol, diethylene glycol. Caustics and other household products: Acidic or alkaline household products, hydrofluoric acid, selenious acid, acetonitrile, methylene chloride. Accidental overdoses continue to occur regularly despite the implementation of various safety measures, including widespread public education, the use of childproof containers, and easy access to poison control centers. In the US, poison control centers receive more than 2.4 million calls annually, with more than 50% involving children younger than 6 years. Most pediatric accidental ingestions involve household cleaning products and analgesics, followed by cosmetics, foreign objects, and dietary supplements. Adult overdoses may be unintentional but often involve larger total doses or high-risk medications, including opioids and sedative-hypnotics. America's Poison Centers identify the 5 most common substance classes as analgesics, household cleaners, antidepressants, cosmetic or personal care items, and cardiovascular drugs. The number of ingestions involving cleaning products increased sharply during the COVID-19 pandemic but has since declined.

The objective was to identify risk factors for long-term sequelae in children with congenital cytomegalovirus (cCMV) infection and to develop a prognostic scoring system (cCMVnet score) to support individualized management. This retrospective study was conducted within the prospective European Registry of Children with cCMV and included 570 children born between 2011 and 2024 in 11 countries. Eligible participants had confirmed cCMV, early cranial ultrasound and brain MRI (≤ 90 days of life), and at least six months of follow-up. The primary outcome was sequelae, defined as sensorineural hearing loss (SNHL), motor impairment, epilepsy, or visual impairment. Predictors were identified using multivariable logistic regression with Elastic-Net selection, followed by development and internal validation of the score. Overall, 63.2% were symptomatic at birth and 28.9% developed sequelae, mainly SNHL (24.7%), motor impairment (8.2%), epilepsy (4.0%), and visual impairment (2.6%). Splenomegaly, severity of hearing loss and neuroimaging abnormalities (white matter changes, calcifications, ventriculomegaly, and cortical malformations/migration abnormalities) were significant predictors. The cCMVnet score showed strong discrimination (AUC 0.872). At a 2.99 point cut-off, sensitivity was 81.3%, specificity 85.3%, and negative predictive value 90.6%.Conclusions: The cCMVnet score enables accurate risk stratification beyond symptomatic status integrating clinical, audiological, and neuroimaging findings. External validation is needed before widespread implementation.

A 45-year-old woman with long-standing hypertension and premature menopause presented with progressive bilateral pitting leg edema. Initial evaluation showed albuminuria, microscopic hematuria and pyuria, severe mixed dyslipidemia, and prediabetes. Despite optimization of blood pressure and cardiometabolic therapy, edema progressed to the thighs, and urinary protein excretion increased. Renal ultrasonography showed increased parenchymal echogenicity, with scarring of the lower half of the left kidney. Subsequent evaluation revealed hypoalbuminemia and nephrotic-range proteinuria of 8.64 g/day. Autoimmune and viral hepatitis screening was negative, and a right renal biopsy confirmed minimal change disease (MCD)/podocytopathy. Treatment with prednisolone 60 mg/day and diuretic therapy led to rapid clinical remission, with complete resolution of edema and reduction of 24-hour urinary protein to 190 mg/day by May 2025 and 55 mg/day by July 2025. The course was complicated by steroid-induced Cushingoid features and worsening glycemia, requiring temporary addition of glimepiride. By March 2026, the patient remained clinically well with excellent lipid and glycemic control. This case highlights the importance of early nephrology referral and kidney biopsy in adults with progressive albuminuria and edema, even when cardiometabolic comorbidities such as hypertension, prediabetes, and severe dyslipidemia coexist.

Background/Objectives: Diabetes mellitus type 2 (T2DM) is often associated with hypertension, necessitating treatment with combinations of medications that address both glycemic control and blood pressure. Whether commonly co-prescribed antihypertensives modify the glycemic efficacy of a sulfonylurea remains insufficiently characterized in controlled preclinical models. Methods: One hundred adult male Wistar rats were allocated to ten parallel groups (n = 10): healthy and diabetic untreated controls; glimepiride, bisoprolol or amlodipine monotherapy (in healthy and diabetic animals); and the diabetic combinations glimepiride+bisoprolol and glimepiride+amlodipine. T2DM was induced with a high-fat diet plus low-dose streptozotocin (35 mg/kg, i.p.) and confirmed by fasting blood glucose ≥ 200 mg/dL. Glycated hemoglobin (HbA1c) was measured weekly for 11 weeks. Non-parametric inference (Kruskal-Wallis, Dunn's with Bonferroni correction, Mann-Whitney U, Wilcoxon signed-rank) was complemented by Random Forest regression and PCA/K-means clustering. Results: Week-11 HbA1c differed markedly across groups (Kruskal-Wallis H = 94.3, p < 0.001). Glimepiride + bisoprolol achieved near-normal control (4.37% ± 0.15), statistically indistinguishable from healthy groups (p ≥ 0.33), and was the only diabetic regimen with a declining trajectory (-0.66 percentage points; Wilcoxon p = 0.004). Adding either antihypertensive to glimepiride did not worsen glycemic control. Amlodipine monotherapy did not attenuate hyperglycemia (8.47% ± 0.20), approaching that of untreated diabetic controls (9.31% ± 0.18), consistent with the absence of intrinsic glucose-lowering activity. All agents showed pronounced disease-state dependence (healthy-diabetic divergence 2.33-3.13 points). Random Forest prediction was accurate (R[2] = 0.985), and unsupervised clustering separated effective from ineffective regimens, corroborating the statistical findings. Conclusions: In this model, bisoprolol co-administration enhanced and amlodipine co-administration preserved glimepiride-mediated glycemic control. Glimepiride+bisoprolol emerged as the most effective regimen, supporting cardioselective β-blockade as a metabolically favorable antihypertensive partner for sulfonylurea therapy and warranting clinical confirmation. More broadly, these results provide a preclinical, evidence-based rationale for selecting metabolically favorable antihypertensives in patients with coexisting T2DM and hypertension, with the potential to improve glycemic outcomes and reduce the risk of adverse drug-disease interactions during combination therapy.