Efficacy and Safety of Vildagliptin and Remogliflozin as Add-on Therapy to Metformin in Patients of Type 2 Diabetes Mellitus: An open-label comparative study.

Objectives: This study aimed to evaluate the safety and efficacy of remogliflozin compared to vildagliptin as an add-on drug to metformin in type 2 diabetes mellitus (T2DM) treatment. Metformin is considered a first-line drug in T2DM. However, as the disease progresses with heightened insulin resistance and declining ß-cell function, the use of metformin alone is often inadequate to achieve optimum glucose levels. Methods: This prospective, randomised study was conducted at Maulana Azad Medical College and Associated Hospital in New Delhi, India, between February 2020 to January 2021. This study recruited 60 T2DM patients aged 35-70 years with glycated haemoglobin (HbA1c) >6.5% taking metformin at a daily dosage of 1,500-3,000 mg for ≥3 months. Patients were randomly assigned in a 1:1 ratio to receive either vildagliptin (50 mg) or remogliflozin (100 mg) twice daily for 90 days. The primary endpoint was a change in HbA1c levels from baseline to the end of 90 days whereas secondary endpoints were changes in lipid profile and weight. Results: The decrement in mean HbA1c levels was significantly higher in the remogliflozin group than in the vildagliptin group (-8.1% versus -2.4%; P <0.001). In addition, more significant weight loss was found in remogliflozin-treated patients (-5.2% versus -0.6%; P <0.01). Both treatments were well tolerated throughout the study. Conclusion: Compared to vildagliptin, remoglilflozin was significantly more effective in glycaemic control and weight loss in patients with T2DM and can therefore be considered as an add-on drug in T2DM not adequately controlled by metformin monotherapy.

Efficacy and Findings of a Blinded Randomized Reintroduction Phase for the Low FODMAP Diet in Irritable Bowel Syndrome.

BACKGROUND & AIMS: The efficacy of a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet in irritable bowel syndrome (IBS) is well established. After the elimination period, a reintroduction phase aims to identify triggers. We studied the impact of a blinded reintroduction using FODMAP powders to objectively identify triggers and evaluated the effect on symptoms, quality of life, and psychosocial comorbidities. METHODS: Responders to a 6-week low FODMAP diet, defined by a drop in IBS symptom severity score (IBS-SSS) compared with baseline, entered a 9-week blinded randomized reintroduction phase with 6 FODMAP powders (fructans, fructose, galacto-oligosaccharides, lactose, mannitol, sorbitol) or control (glucose). A rise in IBS-SSS (≥50 points) defined a FODMAP trigger. Patients completed daily symptom diaries and questionnaires for quality of life and psychosocial comorbidities. RESULTS: In 117 recruited patients with IBS, IBS-SSS improved significantly after the elimination period compared with baseline (150 ± 116 vs 301 ± 97, P < .0001, 80% responders). Symptom recurrence was triggered in 85% of the FODMAP powders, by an average of 2.5 ± 2 FODMAPs/patient. The most prevalent triggers were fructans (56%) and mannitol (54%), followed by galacto-oligosaccharides, lactose, fructose, sorbitol, and glucose (respectively 35%, 28%, 27%, 23%, and 26%) with a significant increase in abdominal pain at day 1 for sorbitol/mannitol, day 2 for fructans/galacto-oligosaccharides, and day 3 for lactose. CONCLUSION: We confirmed the significant benefit of the low FODMAP diet in tertiary-care IBS. A blinded reintroduction revealed a personalized pattern of symptom recurrence, with fructans and mannitol as the most prevalent, and allows the most objective identification of individual FODMAP triggers. Ethical commission University hospital of Leuven reference number: s63629; Clinicaltrials.gov number: NCT04373304.

Gut Microbiota Prevents Sugar Alcohol-Induced Diarrhea.

While poorly-absorbed sugar alcohols such as sorbitol are widely used as sweeteners, they may induce diarrhea in some individuals. However, the factors which determine an individual's susceptibility to sugar alcohol-induced diarrhea remain unknown. Here, we show that specific gut bacteria are involved in the suppression of sorbitol-induced diarrhea. Based on 16S rDNA analysis, the abundance of Enterobacteriaceae bacteria increased in response to sorbitol consumption. We found that Escherichia coli of the family Enterobacteriaceae degraded sorbitol and suppressed sorbitol-induced diarrhea. Finally, we showed that the metabolism of sorbitol by the E. coli sugar phosphotransferase system helped suppress sorbitol-induced diarrhea. Therefore, gut microbiota prevented sugar alcohol-induced diarrhea by degrading sorbitol in the gut. The identification of the gut bacteria which respond to and degrade sugar alcohols in the intestine has implications for microbiome science, processed food science, and public health.

The effect of luseogliflozin on bone microarchitecture in older patients with type 2 diabetes: study protocol for a randomized controlled pilot trial using second-generation, high-resolution, peripheral quantitative computed tomography (HR-pQCT).

BACKGROUND: Older patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fracture independent of their bone mineral density (BMD), which is explained mainly by the deteriorated bone quality in T2DM compared to that in non-diabetic adults. Sodium-glucose co-transporter (SGLT) 2 inhibitors have been studied in several trials in T2DM, and the Canagliflozin Cardiovascular Assessment Study showed an increased fracture risk related to treatment with the SGLT2 inhibitor canagliflozin, although no evidence of increased fracture risk with treatment with other SGLT2 inhibitors has been reported. The mechanism of the difference in the fracture risk between the SGLT2 inhibitors is unknown, but the differences among the SGLT2 inhibitors in the selectivity of SGLT2 against SGLT1 may affect bone metabolism, since among the SGLT2 inhibitors the selectivity of canagliflozin is lowest. We will investigate whether the SGLT2 inhibitor luseogliflozin, which has the higher SGLT2 selectivity, affects bone metabolism by using high-resolution, peripheral quantitative computed tomography (HR-pQCT) which provides direct in vivo morphometric information about the bone microarchitecture. METHODS/DESIGN: This is a single-center, randomized, open-label, active-controlled, parallel pilot trial. Eligible participants are older (age ≥ 60 years) individuals with T2DM with HbA1c levels at 7.0-8.9%. A total of 24 participants will be allocated to either the luseogliflozin group (taking luseogliflozin) or the control group (taking metformin) in a 1:1 ratio to compare the groups' changes in bone microarchitecture of the radius and tibia which are analyzed by HR-pQCT before and at 48 weeks after the administration of each medication. The laboratory data associated with glycemic control and bone metabolism will be collected every 12 weeks during the study. Recruitment began in June 2019. DISCUSSION: The reason that we use metformin as an active control is to avoid yielding differences in glycemic control between the luseogliflozin and control groups. Besides, metformin is considered to have a neutral effect on bone. This trial should reveal the effect of luseogliflozin on bone metabolism in older patients with T2DM. TRIAL REGISTRATION: The study was registered with the University Hospital Medical Information Network (UMIN000036202) on 1 April 2019 and with the Japan Registry of Clinicla Trials (jRCTs071180061) on 14 March 2019.

Investigation and Management of Stool Frequency and Consistency Associated With SGLT1 Inhibition by Reducing Dietary Carbohydrate: A Randomized Trial.

Treatment with licogliflozin, a dual sodium-glucose co-transporter (SGLT)1/2-inhibitor, is associated with increased stool frequency and loose stools, attributed to SGLT1 inhibition. To investigate the effect of carbohydrate content and supplements on licogliflozin-induced stools, a randomized, open-label, two-part (N = 24/part), three-period crossover study was carried out in overweight or obese adults. Significantly higher (P < 0.01) change from baseline in 3-day total number of bowel movements was observed following 3 days of licogliflozin treatment (50 mg q.d.) together with a 50% carbohydrate meal compared with a 25% and 0% carbohydrate meal. The number of stools with Bristol Stool Chart score of 6 or 7 was also significantly lower following a 0% carbohydrate meal. Supplementation with psyllium 6 g or calcium carbonate 1 g had no effect on stool changes following treatment. Licogliflozin was generally safe and well-tolerated. Loose stool associated with licogliflozin treatment and ingestion of meals can be managed by reducing the carbohydrate content of meals taken with licogliflozin.

Luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, preserves renal function irrespective of acute changes in the estimated glomerular filtration rate in Japanese patients with type 2 diabetes.

Acute decline in estimated glomerular filtration rate (eGFR), a typical finding after initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors, is associated with maintaining renal function in type 2 diabetes. However, the relationship between the magnitude of acute decline in eGFR and the course of eGFR thereafter is not known. A pooled analysis of four 52-week phase III trials of luseogliflozin 2.5 mg daily (or up to 5 mg daily) in Japanese patients with type 2 diabetes was conducted and stratified according to the tertile of magnitude of acute change in eGFR during the 2 weeks after initiation. The mean age, glycated hemoglobin, eGFR, and urinary albumin were 60 years, 7.8%, 79.6 mL/min/1.73 m2, and 62.7 mg/g Cr, respectively. Acute change in eGFR varied widely between patients (N = 941; mean, -2.3; min, -35.5; max, 27.6). Patients with greater acute decline in eGFR, characterized by higher baseline eGFR and increased diuretic use, showed rapid recovery and maintenance of eGFR thereafter. Higher eGFR, longer duration of diabetes, and higher body mass index and diuretic use were associated with greater acute decline in eGFR. The course of eGFR from 12 to 52 weeks was maintained regardless of acute changes. Although acute changes in eGFR varied widely among patients with type 2 diabetes, the course of eGFR thereafter was stable regardless of the degree of acute changes.

The efficacy and safety of luseogliflozin and sitagliptin depending on the sequence of administration in patients with type 2 diabetes mellitus: a randomized controlled pilot study.

Background: The efficacy and safety of SGLT-2 and DPP-4 inhibitor monotherapies in T2DM is well established; however, data on the effect of combination therapies and sequence of administration are lacking. We investigated the efficacy and safety of the sequence of SGLT-2 and DPP-4 inhibitor administration in Japanese T2DM patients.Research design and methods: In this single-institution, open-label, randomized controlled study, T2DM patients inadequately controlled (HbA1c ≥6.5%) with conventional therapy were randomized to receive luseogliflozin-sitagliptin (LS; luseogliflozin 2.5 mg for 0-12 weeks, then luseogliflozin plus sitagliptin 50 mg for 12-24 weeks) or sitagliptin-luseogliflozin (SL; sitagliptin 50 mg for 0-12 weeks, then sitagliptin plus luseogliflozin 2.5 mg for 12-24 weeks). The main outcome was the difference in mean change in HbA1c at 24 weeks relative to baseline between both groups.Results: Of the 41 enrolled and randomized patients, 34 completed the study. Mean ± SD HbA1c at baseline was 10.35 ± 1.04% and 10.02 ± 1.40% in the LS and SL groups, respectively, and mean ± SD change in HbA1c at 24 weeks from baseline was -3.81 ± 1.21% vs -2.46 ± 1.42% (P < 0.01), respectively. No drug-related adverse events were reported.Conclusion: Over the 24-week period, LS was more effective in reducing HbA1c levels than SL in Japanese T2DM patients.

The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes.

BACKGROUND: There is an unmet need for a safer and more effective treatment for obesity. This study assessed the effects of licogliflozin, a dual inhibitor of sodium-glucose co-transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with type 2 diabetes mellitus (T2DM) and/or obesity. METHODS: Patients with obesity (BMI, 35-50 kg/m2 ) were enrolled into a 12-week study (N = 88; licogliflozin 150 mg q.d.). Patients with T2DM were enrolled into a second, two-part study, comprising a single-dose cross-over study (N = 12; 2.5 - 300 mg) and a 14-day dosing study (N = 30; 15 mg q.d). Primary endpoints included effects on body weight, effects on glucose, safety and tolerability. Secondary endpoints included urinary glucose excretion (UGE24 ) and pharmacokinetics, while exploratory endpoints assessed the effects on incretin hormones (total GLP-1, PYY3-36 , and GIP), insulin and glucagon. RESULTS: Treatment with licogliflozin 150 mg q.d. for 12 weeks in patients with obesity significantly reduced body weight by 5.7% vs placebo (P < 0.001) and improved metabolic parameters such as significantly reduced postprandial glucose excursion (21%; P < 0.001), reduced insulin levels (80%; P < 0.001) and increased glucagon (59%; P < 0.001). In patients with T2DM, a single dose of licogliflozin 300 mg in the morning prior to an oral glucose tolerance test (OGTT) remarkably reduced glucose excursion by 93% (P < 0.001; incremental AUC0-4h ) and suppressed insulin by 90% (P < 0.01; incremental AUC0-4h ). Treatment with licogliflozin 15 mg q.d. for 14 days reduced 24-hour average glucose levels by 26% (41 mg/dL; P < 0.001) and increased UGE24 to 100 g (P < 0.001) in patients with T2DM. In addition, this treatment regimen significantly increased total GLP-1 by 54% (P < 0.001) and PYY3-36 by 67% (P < 0.05) post OGTT vs placebo, while significantly reducing GIP levels by 53% (P < 0.001). Treatment with licogliflozin was generally safe and well tolerated. Diarrhea (increased numbers of loose stool) was the most common adverse event in all studies (90% with licogliflozin vs 25% with placebo in the 12-week study), while a lower incidence of flatulence, abdominal pain and abdominal distension (25%-43% with licogliflozin vs 9%-11% with placebo in the 12-week study) were among the other gastrointestinal events reported. CONCLUSION: Licogliflozin treatment (1-84 days) leads to significant weight loss and favourable changes in a variety of metabolic parameters and incretin hormones. Dual inhibition of SGLT1/2 with licogliflozin in the gut and kidneys is an attractive strategy for treating obesity and diabetes.

SMOFlipid Protects Preterm Neonates against Perinatal Nutrition-Associated Cholestasis.

OBJECTIVE: Intravenous lipid infusions improve both short- and long-term outcomes of premature neonates. However, prolonged infusion of lipids has been implicated in the development of parenteral nutrition-associated cholestasis (PNAC). We speculated that the multicomponent SMOFlipid would be hepatoprotective against PNAC. STUDY DESIGN: This is a retrospective review comparing the incidence and severity of direct hyperbilirubinemia in preterm infants <1,500 g who were hospitalized for a minimum of 2 weeks during a 20-month period in which all preterm infants on total parenteral nutrition (TPN) received fat as Lipofundin with the following 20-month period in which all preterm infants on TPN received SMOFlipid. RESULTS: Infants in the SMOFlipid period had a lower incidence of PNAC (6 vs. 13%; p = 0.022), lower peak direct bilirubin levels (3.2 vs. 7.1 mg/dL; p = 0.018), and a shorter length of stay (51 vs. 60 days; p = 0.019). The relative risk of developing direct hyperbilirubinemia during the Lipofundin period was 2.22 (1.1-4.3) as compared with period 1; p = 0.018; NNT-14. CONCLUSION: SMOFlipid was hepatoprotective in our population of preterm neonates <1,500 g receiving long-term TPN as compared with those receiving Lipofundin, despite similar levels of exposure to both intravenous lipid load and duration in the two groups.

Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study): study protocol for a randomized, controlled, multicenter, international clinical trial.

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017.

Effects of Sorbitol on the Pharmacokinetics of Lamivudine Solution and the FDA's Decision to Increase the Dose of Lamivudine Solution for Pediatric Patients.

The article by Adkison et al. described sorbitol effects on lamivudine exposures. The results indicate a plausible mechanism for lower lamivudine exposures in pediatric patients receiving the solution formulation with concomitant medications containing sorbitol. In this commentary, we discuss lower lamivudine exposures in pediatric patients receiving the solution formulation, the impact of sorbitol on lamivudine exposures, and the US Food and Drug Administration's (FDA's) decision to increase the dose of the lamivudine solution for all pediatric patients.

Rectal ulcer due to Kayexalate deposition - an unusual case

SUMMARY Sodium polystyrene sulfonate (PSP) or Kayexalate is a cation-exchange resin, widely used in the management of hyperkalaemia due to renal disease. A rare, yet potentially dangerous, adverse event related to sodium polystyrene sulfonate use is intestinal mucosal injury, especially in the colon. The injury to the gastrointestinal mucosa can range from mild and superficial to wall necrosis and bowel perforation. The mechanism that leads to mucosal damage remains unclear. However, it is believed that sorbitol, commonly given to counteract PSP's tendency to cause constipation, may play an important role in the development of gastrointestinal injury. Other potential risk factors are uraemia or end-stage renal disease, hemodynamic instability, solid organ transplantation, postoperative status and concomitant opioid administration. The authors present a case of diarrhoea and haematochezia after the administration of PSP without sorbitol, in a patient with hyperkalaemia due to acute kidney injury, in the absence of other risk factors. A colonoscopy was performed and revealed a rectal ulcer which histological findings were suggestive of mucosal injury due to Kayexalate deposition. This case supports the concept that this widely used drug can itself, without sorbitol, cause injury to the gastrointestinal wall. Even though this is a rare adverse effect, the widespread use of this medication may put a large population at risk.

RESUMO O polistireno sulfonato de sódio (PSP) ou kayexalato é uma resina de troca iônica, amplamente usada no tratamento da hipercalemia associada à doença renal. Um efeito adverso raro, mas potencialmente grave, dessa terapêutica é a agressão à parede do trato gastrointestinal, principalmente ao nível do cólon, que pode ser ligeira e superficial ou culminar em necrose e perfuração intestinal. O mecanismo pelo qual o PSP lesa a mucosa intestinal não é totalmente conhecido. Contudo, pensa-se que o sorbitol, frequentemente administrado em simultâneo para contrabalançar o efeito obstipante do PSP, possa ter um papel preponderante no desenvolvimento de lesão gastrointestinal. Outros potenciais fatores de risco são a presença de uremia ou doença renal em estágio terminal, instabilidade hemodinâmica, pós-operatório, pós-transplante renal e a administração concomitante de opioides. Os autores descrevem um caso de diarreia e hematoquesias após a administração de PSP sem sorbitol, numa paciente com hipercalemia secundária a lesão renal aguda, sem outros fatores de risco para o desenvolvimento desse efeito adverso. A investigação etiológica com colonoscopia revelou a presença de uma úlcera retal, cujo estudo histológico foi compatível com lesão por deposição de cristais de kayexalato. Este relato incomum reforça o conceito de que este fármaco de uso frequente, mesmo na ausência de sorbitol, pode ser lesivo para a mucosa intestinal. Assim, e apesar de este ser um efeito adverso raro, a utilização difundida do PSP coloca uma vasta população em risco.

Pharmacokinetics and Pharmacodynamics of Luseogliflozin, a Selective SGLT2 Inhibitor, in Japanese Patients With Type 2 Diabetes With Mild to Severe Renal Impairment.

This open-label, parallel-group, multicenter study aimed to assess the effects of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of luseogliflozin. A single 5-mg dose of luseogliflozin was administered to Japanese patients with type 2 diabetes mellitus in the following groups: G1, normal renal function; G2, mild renal impairment; G3a, mild to moderate impairment; G3b, moderate to severe impairment; G4, severe impairment, based on estimated glomerular filtration rate (eGFR; ≥90, 60-89, 45-59, 30-44, 15-29 mL/min/1.73 m2 , respectively). While luseogliflozin pharmacokinetics were similar for patients across all renal function groups, the increase in plasma concentration was slightly slower and maximum concentration was slightly reduced in the lower eGFR groups compared with the other groups. However, luseogliflozin pharmacodynamics were affected by the severity of renal impairment. Urinary glucose excretion (UGE) increased in all groups relative to baseline levels, but the degree of UGE increase was smaller in the lower eGFR groups. Moreover, plasma glucose AUC changes from baseline tended to be smaller in the lower eGFR groups. No clear trends were observed between eGFR and incidence, type, or severity of adverse events. Thus, luseogliflozin administration should be carefully considered, as patients with renal impairment may show an insufficient response to treatment.

Sodium-glucose cotransporter-2 inhibitor luseogliflozin added to glucagon-like peptide 1 receptor agonist liraglutide improves glycemic control with bodyweight and fat mass reductions in Japanese patients with type 2 diabetes: A 52-week, open-label, single-arm study.

AIMS/INTRODUCTION: The aim of the present study was to evaluate the safety and efficacy of luseogliflozin added to liraglutide monotherapy in Japanese individuals with type 2 diabetes. MATERIALS AND METHODS: This 52-week, multicenter, open-label, single-arm clinical study enrolled Japanese patients who had inadequate glycemic control with diet/exercise and liraglutide monotherapy. Major efficacy end-points included the changes from baseline in glycated hemoglobin, fasting plasma glucose and bodyweight. Body composition was also assessed in individuals who had access to bioelectrical impedance analysis. Safety assessments included adverse events, clinical laboratory tests, vital signs and 12-lead electrocardiograms. RESULTS: Of 76 patients who received luseogliflozin, 62 completed the study. The changes from baseline in glycated hemoglobin, fasting plasma glucose, and bodyweight (mean ± SE) were -0.68 ± 0.10%, -32.1 ± 3.6 mg/dL and -2.71 ± 0.24 kg at week 52, respectively (all, P < 0.001 vs baseline). Luseogliflozin was associated with greater reductions in fat mass than lean mass at all measuring points (n = 22): fat vs lean mass changes (mean ± SE) at week 52 were -2.49 ± 0.45 kg (P < 0.001 vs baseline) and -0.44 ± 0.26 kg (P = 0.107 vs baseline), respectively. Insulin secretion and Matsuda Index were also improved at weeks 12 and 52 compared with baseline. Adverse events and adverse drug reactions occurred in 65.8 and 27.6% of patients, respectively. The overall safety profile, including frequency of hypoglycemia, was found to be consistent with those of previous studies and there were no new safety concerns. CONCLUSIONS: Luseogliflozin added to liraglutide was well tolerated, and improved glycemic control with bodyweight and fat mass reductions in Japanese type 2 diabetes patients.

Luseogliflozin improves liver fat deposition compared to metformin in type 2 diabetes patients with non-alcoholic fatty liver disease: A prospective randomized controlled pilot study.

This study aimed to assess the effect of luseogliflozin on liver fat deposition and compare luseogliflozin to metformin in type 2 diabetes (T2D) patients with non-alcoholic fatty liver disease (NAFLD). Thirty-two T2D patients with NAFLD diagnosed by computed tomography or abdominal sonography were recruited. Participants were randomly assigned to receive either luseogliflozin (2.5 mg, newly administered) or metformin (1500 mg, newly or additionally administrated). Data on the liver-to-spleen attenuation ratio (L/S), visceral fat area, body mass index, glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), fasting plasma glucose, C-peptide immunoreactivity (CPR), and CPR index were collected at baseline and after 6 months. The change in L/S was significantly greater in the luseogliflozin group than in the metformin group. Similarly, the changes in the visceral fat area, HbA1c, and body mass index were significantly greater in the luseogliflozin group than in the metformin group. The changes in ALT, fasting glucose, CPR, and CPR index were not significant in both groups. In conclusion, luseogliflozin significantly reduced liver fat deposition as compared to metformin, which may indicate clinical relevant benefits for NAFLD.

Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open-Label, Randomized Study.

In children aged ≤4 years, the relative bioavailability of lamivudine oral solution was 37% lower than that of a tablet formulation. An open-label, four-way crossover study was conducted in healthy adults to evaluate the effect of sorbitol, a common liquid excipient, on the pharmacokinetics of lamivudine oral solution (ClinicalTrials.gov identifier, NCT02634073). Sixteen subjects were randomized to one of four sequences consisting of four doses of lamivudine 300 mg (10 mg/mL) alone or with sorbitol 3.2, 10.2, or 13.4 g. Sorbitol 3.2, 10.2, and 13.4 g decreased lamivudine maximum concentration (Cmax ) by 28%, 52%, and 55% and area under the concentration-time curve from time 0 to 24 h (AUC0-24 ) by 20%, 39%, and 44%, respectively. Three subjects (19%) reported five nonserious adverse events (one drug-related). The dose-dependent effects of sorbitol on lamivudine Cmax and AUC0-24 reveal an absorption-based interaction that may decrease lamivudine exposure in patients coadministered sorbitol-containing medicines.

Rectal ulcer due to Kayexalate deposition - an unusual case.

Sodium polystyrene sulfonate (PSP) or Kayexalate is a cation-exchange resin, widely used in the management of hyperkalaemia due to renal disease. A rare, yet potentially dangerous, adverse event related to sodium polystyrene sulfonate use is intestinal mucosal injury, especially in the colon. The injury to the gastrointestinal mucosa can range from mild and superficial to wall necrosis and bowel perforation. The mechanism that leads to mucosal damage remains unclear. However, it is believed that sorbitol, commonly given to counteract PSP's tendency to cause constipation, may play an important role in the development of gastrointestinal injury. Other potential risk factors are uraemia or end-stage renal disease, hemodynamic instability, solid organ transplantation, postoperative status and concomitant opioid administration. The authors present a case of diarrhoea and haematochezia after the administration of PSP without sorbitol, in a patient with hyperkalaemia due to acute kidney injury, in the absence of other risk factors. A colonoscopy was performed and revealed a rectal ulcer which histological findings were suggestive of mucosal injury due to Kayexalate deposition. This case supports the concept that this widely used drug can itself, without sorbitol, cause injury to the gastrointestinal wall. Even though this is a rare adverse effect, the widespread use of this medication may put a large population at risk.