Tirzepatide Reduces Fat Mass and Provides Good Glycaemic Control in Type 2 Diabetes Patients Undergoing Haemodialysis: A Single-Centre Retrospective Study.

OBJECTIVE: Tirzepatide is an injectable peptide approved by the US Food and Drug Administration for the treatment of Type 2 diabetes (T2DM). Its weight-loss effect primarily targets fat reduction; however, such effect on patients with chronic kidney disease (CKD) undergoing haemodialysis (HD) has not been reported. METHODS: Nine patients with CKD undergoing HD received weekly tirzepatide doses (2.5-7.5 mg) once a week. Evaluations encompassed tirzepatide's impact on dry weight (DW) and body composition assessed at baseline and study conclusion using bioelectrical impedance analysis. This longitudinal study included nine patients, with a median age of 53 years and median HD duration of 4 years. RESULTS: Tirzepatide treatment significantly decreased glycated albumin compared with the value at baseline (22.7 ± 5.4 vs. 18.3 ± 2.5%, p = 0.028, respectively). Significant reductions were observed in DW (-1.0 kg, p = 0.024) and body mass index (-0.6 kg/m2, p = 0.050) following tirzepatide administration. Total fat mass was also reduced, but not significantly (- 2.51% from baseline, p = 0.214). In contrast, skeletal muscle mass was not decreased (-1.02% from baseline, p = 0.722). No serious side effects other than nausea were observed during the study period. CONCLUSION: Tirzepatide effectively provides good glycaemic control in T2DM patients undergoing HD, decreasing DW by reducing body fat mass without increasing frailty risk.

Improvement of phenolic profile and biological activities of wild mustard sprouts.

The current study aimed to assess the effect of the germination process of wild mustard seeds on the phenolic profile, antioxidant, antibacterial, and antidiabetic properties, and some relevant enzyme activities. The total phenolic and flavonoid contents increased 5- and 10-fold, respectively, and were maximized on 5-days sprouts. One new phenolic compound was identified on 5-days sprout extract using HPLC. The concentrations of the identified phenolic compounds increased 1.5-4.3 folds on 5-days sprouts compared with dry seeds. The total antioxidant activity multiplied 17- and 21-fold on 5-days sprouts using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays, respectively. The activity of carbohydrate-cleaving, phenolic-synthesizing and antioxidant enzymes also increased during germination. On 5-days sprouts, there was a substantial correlation between the highest ß-glucosidase and peroxidase activities with highest phenolic and flavonoid levels and maximum antioxidant activity. The phenolic extract of 5-days sprouts exhibited antimicrobial activities against Escherichia coli and Staphylococcus aureus and showed potent antidiabetic activity established by its inhibitory effect against α-amylase and α-glucosidase compared to dry seeds.

Association of RASGRP1 polymorphism with vascular complications in Chinese diabetic patients with glycemic control and antihypertensive treatment.

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.

Significant elevation of serum CA19-9 and CA242 levels induced by dulaglutide.

The use of dulaglutide, a common medication for managing type 2 diabetes, rarely causes elevated pancreatic tumour markers. Here, we report the case of a woman in her mid-60s with diabetes for over 10 years. The patient presented with markedly elevated serum CA19-9 and CA242 levels revealed during a routine health examination despite being asymptomatic. She had been receiving dulaglutide injections for 16 months. Imaging and interventional assessments did not reveal any hepatobiliary, gastrointestinal or pancreatic neoplasm. After excluding alternate diagnoses, the patient was determined to exhibit an adverse reaction to dulaglutide use. Management involved the discontinuation of dulaglutide, which resulted in normalisation of serum CA19-9 and CA242 levels within 6 weeks. This case underscores the importance of discontinuing dulaglutide and monitoring changes in the biomarker levels in asymptomatic patients receiving dulaglutide, rather than immediately resorting to imaging and endoscopic examinations.

Metformin attenuates lung ischemia-reperfusion injury and necroptosis through AMPK pathway in type 2 diabetic recipient rats.

BACKGROUND: Diabetes mellitus (DM) can aggravate lung ischemia-reperfusion (I/R) injury and is a significant risk factor for recipient mortality after lung transplantation. Metformin protects against I/R injury in a variety of organs. However, the effect of metformin on diabetic lung I/R injury remains unclear. Therefore, this study aimed to observe the effect and mechanism of metformin on lung I/R injury following lung transplantation in type 2 diabetic rats. METHODS: Sprague-Dawley rats were randomly divided into the following six groups: the control + sham group (CS group), the control + I/R group (CIR group), the DM + sham group (DS group), the DM + I/R group (DIR group), the DM + I/R + metformin group (DIRM group) and the DM + I/R + metformin + Compound C group (DIRMC group). Control and diabetic rats underwent the sham operation or left lung transplantation operation. Lung function, alveolar capillary permeability, inflammatory response, oxidative stress, necroptosis and the p-AMPK/AMPK ratio were determined after 24 h of reperfusion. RESULTS: Compared with the CIR group, the DIR group exhibited decreased lung function, increased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, but decreased the p-AMPK/AMPK ratio. Metformin improved the function of lung grafts, decreased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, and increased the p-AMPK/AMPK ratio. In contrast, the protective effects of metformin were abrogated by Compound C. CONCLUSIONS: Metformin attenuates lung I/R injury and necroptosis through AMPK pathway in type 2 diabetic lung transplant recipient rats.

Cardiovascular and mortality benefits of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists as third-step glucose-lowering medicine in patients with type 2 diabetes: a retrospective cohort analysis.

INTRODUCTION: Studies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). The literature does not provide evidence specifically for patients with these conditions who are adding one of these medicines to two glucose-lowering medications (ie, as "third-step" therapy). We explored the effects of different third-step medications on cardiovascular outcomes in patients with diabetes and these comorbid conditions. Specifically, we compared third-step SGLT2 or GLP1 to third-step dipeptidyl peptidase-4 inhibitors (DPP4), insulin, or thiazolidinediones (TZD). RESEARCH DESIGN AND METHODS: We assembled a retrospective cohort of adults at five Kaiser Permanente sites with DM2 and ASCVD, CKD, or HF, initiating third-step treatment between 2016 and 2020. Propensity score weighted Poisson models were used to calculate adjusted rate ratios (ARRs) for all-cause mortality, incident major adverse cardiovascular event (MACE), and incident HF hospitalization in patients initiating SGLT2 or GLP1 compared with DPP4, insulin, or TZD. RESULTS: We identified 27 542 patients initiating third-step treatment with one or more of these conditions (19 958 with ASCVD, 14 577 with CKD, and 3919 with HF). ARRs for GLP1 and SGLT2 versus DPP4, insulin, and TZD in the patient subgroups ranged between 0.22 and 0.55 for all-cause mortality, 0.38 and 0.81 for MACE, and 0.46 and 1.05 for HF hospitalization. Many ARRs were statistically significant, and all significant ARRs showed a benefit (ARR <1) for GLP1 or SGLT2 when compared with DPP4, insulin, or TZD. CONCLUSIONS: Third-step SGLT2 and GLP1 are generally associated with a benefit for these outcomes in these patient groups when compared with third-step DPP4, insulin, or TZD. Our results add to evidence of a cardiovascular benefit of SGLT2 and GLP1 and could inform clinical guidelines for choosing third-step diabetes treatment.

Effects of metformin, saxagliptin and repaglinide on gut microbiota in high-fat diet/streptozocin-induced type 2 diabetic mice.

INTRODUCTION: There has been increasing evidence that the gut microbiota is closely related to type 2 diabetes (T2D). Metformin (Met) is often used in combination with saxagliptin (Sax) and repaglinide (Rep) for the treatment of T2D. However, little is known about the effects of these combination agents on gut microbiota in T2D. RESEARCH DESIGN AND METHODS: A T2D mouse model induced by a high-fat diet (HFD) and streptozotocin (STZ) was employed. The T2D mice were randomly divided into six groups, including sham, Met, Sax, Rep, Met+Sax and Met+Rep, for 4 weeks. Fasting blood glucose level, serum biochemical index, H&E staining of liver, Oil red O staining of liver and microbiota analysis by 16s sequencing were used to access the microbiota in the fecal samples. RESULTS: These antidiabetics effectively prevented the development of HFD/STZ-induced high blood glucose, and the combination treatment had a better effect in inhibiting lipid accumulation. All these dosing regimens restored the decreasing ratio of the phylum Bacteroidetes: Firmicutes, and increasing abundance of phylum Desulfobacterota, expect for Met. At the genus level, the antidiabetics restored the decreasing abundance of Muribaculaceae in T2D mice, but when Met was combined with Rep or Sax, the abundance of Muribaculaceae was decreased. The combined treatment could restore the reduced abundance of Prevotellaceae_UCG-001, while Met monotherapy had no such effect. In addition, the reduced Lachnospiraceae_NK4A136_group was well restored in the combination treatment groups, and the effect was much greater than that in the corresponding monotherapy group. Therefore, these dosing regimens exerted different effects on the composition of gut microbiota, which might be associated with the effect on T2D. CONCLUSIONS: Supplementation with specific probiotics may further improve the hypoglycemic effects of antidiabetics and be helpful for the development of new therapeutic drugs for T2D.

A systematic review on reporting quality of economic evaluations for negotiated glucose-lowering drugs in China national reimbursement drug list.

BACKGROUND: This study aimed to examine the reporting quality of existing economic evaluations for negotiated glucose-lowering drugs (GLDs) included in China National Reimbursement Drug List (NRDL) using the Consolidated Health Economic Evaluation Reporting Standards 2013 (CHEERS 2013). METHODS: We performed a systematic literature research through 7 databases to identify published economic evaluations for GLDs included in the China NRDL up to March 2021. Reporting quality of identified studies was assessed by two independent reviewers based on the CHEERS checklist. The Kruskal-Wallis test and Mann-Whitney U test were performed to examine the association between reporting quality and characteristics of the identified studies. RESULTS: We have identified 24 studies, which evaluated six GLDs types. The average score rate of the included studies was 77.41% (SD:13.23%, Range 47.62%-91.67%). Among all the required reporting items, characterizing heterogeneity (score rate = 4.17%) was the least satisfied item. Among six parts of CHEERS, results part scored least at 0.55 (score rate = 54.79%) because of the incompleteness of characterizing uncertainty. Results from the Kruskal-Wallis test and Mann-Whitney U test showed that model choice, journal type, type of economic evaluations, and study perspective were associated with the reporting quality of the studies. CONCLUSIONS: There remains room to improve the reporting quality of economic evaluations for GLDs in NRDL. Checklists such as CHEERS should be widely used to improve the reporting quality of economic researches in China.

Metformin for endometrial hyperplasia.

BACKGROUND: Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets that are currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. A levonorgestrel intrauterine device may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown, in some human studies, to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. This is an update of a review first published in 2017. OBJECTIVES: To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, PubMed, Embase, Google Scholar, OpenGrey, LILACS, and two trials registers from inception to 5 September 2022. We searched the bibliographies of all relevant studies, and contacted experts in the field for any additional trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo, no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, extracted data from included studies, assessed the risk of bias in the included studies, and assessed the certainty of the evidence for each outcome. We resolved disagreements by discussion or by deferring to a third review author. When study details were missing, review authors contacted the study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. MAIN RESULTS: We included seven RCTs, in which a total of 387 women took part. In the comparison, Metformin plus megestrol versus megestrol alone, we rated the certainty of the evidence as low for the outcome, regression of endometrial hyperplasia. We rated the quality of the evidence as very low for the rest of the outcomes, in all three comparisons. Although there was a low risk of selection bias, there was a high risk of bias in the blinding of personnel and outcome assessment (performance bias and detection bias) in many studies. This update identified four new RCTs and six ongoing RCTs. Metformin versus megestrol We are uncertain whether metformin increases the regression of endometrial hyperplasia towards normal histology over megestrol (odds ratio (OR) 4.89, 95% confidence interval (CI) 1.56 to 15.32; P = 0.006; 2 RCTs, 83 participants; I² = 7%; very low-certainty evidence). This evidence suggests that if the rate of regression with megestrol is 61%, the rate of regression with metformin would be between 71% and 96%. It is unresolved whether metformin results in different rates of abnormal uterine bleeding or hysterectomy compared to megestrol. No study in this comparison reported progression of hyperplasia to endometrial cancer, recurrence of endometrial hyperplasia, health-related quality of life, or adverse effects during treatment. Metformin plus megestrol versus megestrol monotherapy The combination of metformin and megestrol may enhance the regression of endometrial hyperplasia towards normal histology more than megestrol alone (OR 3.27, 95% CI 1.65 to 6.51; P = 0.0007; 4 RCTs, 258 participants; I² = 0%, low-certainty evidence). This suggests that if the rate of regression with megestrol monotherapy is 54%, the rate of regression with the addition of metformin would be between 66% and 84%. In one study, 3/8 (37.5%) of participants who took metformin had nausea that settled without further treatment. It is unresolved whether the combination of metformin and megestrol results in different rates of recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, or hysterectomy compared to megestrol monotherapy. No study in this comparison reported abnormal uterine bleeding, or health-related quality of life. Metformin plus levonorgestrel (intrauterine system) versus levonorgestrel (intrauterine system) monotherapy We are uncertain whether there is a difference between groups in the regression of endometrial hyperplasia towards normal histology (OR 0.29, 95% CI 0.01 to 7.56; 1 RCT, 46 participants; very low-certainty evidence). This evidence suggests that if the rate of regression with levonorgestrel monotherapy is 96%, the rate of regression with the addition of metformin would be between 73% and 100%. It is unresolved whether the combination of metformin and levonorgestrel results in different rates of abnormal uterine bleeding, hysterectomy, or the development of adverse effects during treatment compared to levonorgestrel monotherapy. No study in this comparison reported recurrence of endometrial hyperplasia, progression of hyperplasia to endometrial cancer, or health-related quality of life. AUTHORS' CONCLUSIONS: Review authors found insufficient evidence to either support or refute the use of metformin, specifically megestrol acetate, given alone or in combination with standard therapy, for the treatment of women with endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials, yielding long-term outcome data are still needed to address this clinical question.

Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

GLP-1 receptor agonist improves metabolic disease in a pre-clinical model of lipodystrophy.

Aims: Individuals with lipodystrophies typically suffer from metabolic disease linked to adipose tissue dysfunction including lipoatrophic diabetes. In the most severe forms of lipodystrophy, congenital generalised lipodystrophy, adipose tissue may be almost entirely absent. Better therapies for affected individuals are urgently needed. Here we performed the first detailed investigation of the effects of a glucagon like peptide-1 receptor (GLP-1R) agonist in lipoatrophic diabetes, using mice with generalised lipodystrophy. Methods: Lipodystrophic insulin resistant and glucose intolerant seipin knockout mice were treated with the GLP-1R agonist liraglutide either acutely preceding analyses of insulin and glucose tolerance or chronically prior to metabolic phenotyping and ex vivo studies. Results: Acute liraglutide treatment significantly improved insulin, glucose and pyruvate tolerance. Once daily injection of seipin knockout mice with liraglutide for 14 days led to significant improvements in hepatomegaly associated with steatosis and reduced markers of liver fibrosis. Moreover, liraglutide enhanced insulin secretion in response to glucose challenge with concomitantly improved glucose control. Conclusions: GLP-1R agonist liraglutide significantly improved lipoatrophic diabetes and hepatic steatosis in mice with generalised lipodystrophy. This provides important insights regarding the benefits of GLP-1R agonists for treating lipodystrophy, informing more widespread use to improve the health of individuals with this condition.

Functional insulin therapy in type 1 diabetics: Short-term effects on weight and nutritional intake.

INTRODUCTION-AIM: Flexible insulin therapy is currently considered the gold standard therapy of type 1 diabetes. We aimed to study the evolution of glycemic control, weight and nutritional intake of a group of patients with type 1 diabetes, three months after the initiation of functional insulin therapy (FIT). METHODS: This was a prospective longitudinal study having included 30 type 1 diabetic patients hospitalized for education to FIT. Each patient underwent an assessment of glycemic control (glycated hemoglobin (A1C) and number of hypoglycemia), weight and nutritional intake before FIT and 3 months after the initiation of this educative approach. RESULTS: The mean age of patients was 21,8 ± 7,9 years and the sex ratio was 0,5. The mean duration of diabetes was 7,2 ± 6 years. Three months after initiation of FIT, we observed a significant lowering of A1C, which went from 9,2 ± 1,6% to 8,3 ± 1,4% (p<0,001) of the number of minor hypoglycemia (p=0,001) and that of severe hypoglycemia (p= 0,021). the average weight went from 64,6 ± 13,1 kg to 65,5 ± 13,5 kg (p = 0,040) with a significant increase in BMI (p = 0,041). Weight gain was observed in 67% of patients. This weight gain contrasted with a significant decrease in caloric (p = 0,040) and in carbohydrates intakes (p = 0,027). CONCLUSION: Weight gain, associated with better glycemic control, should encourage the healthcare team to strengthen therapeutic education of patients undergoing FIT in order to limit weight gain.

Shared decision-making approach to type 2 diabetes management.

OBJECTIVE: To provide an online interactive decision aid to facilitate shared decision making in the context of medication choices for patients with type 2 diabetes mellitus (T2DM). SOURCES OF INFORMATION: The best available clinical prediction model for patients with T2DM was selected based on a review of guidelines, DynaMed, and UpToDate and a search of PubMed. A list of pharmacotherapeutic options for T2DM was compiled based on a review of guidelines, narrative reviews, and expert opinion. To determine the benefits and harms of each treatment, federated search engines were searched for meta-analyses of randomized controlled trials, supplemented by individual randomized controlled trials for outcomes not reported in meta-analyses. MAIN MESSAGE: Approximately 2.1 million Canadians have T2DM, with a resulting increased risk of death, cardiovascular disease, and microvascular outcomes. While more than a dozen medication options are available, decisions regarding these medications are challenging, as patients vary in their preferences. Shared decision making has the potential to individualize these difficult decisions, but the number of diabetes-related outcomes and available treatment options have made this historically impractical. It is within this context that the PEER Diabetes Medication Decision Aid was developed. This decision aid provides patients with personalized 10-year risk estimates for 6 clinically important diabetes-related outcomes. The tool also allows patients to focus on the outcome that matters most to them and to compare the benefits and harms of up to 12 different treatment options. This information is displayed in personalized absolute numbers, along with practical considerations such as cost. CONCLUSION: The PEER Diabetes Medication Decision Aid provides a practical tool that can enable patients with T2DM to come to autonomous and well-informed medication decisions.

Summary of clinical investigation plan for The DIATEC trial: in-hospital diabetes management by a diabetes team and continuous glucose monitoring or point of care glucose testing - a randomised controlled trial.

BACKGROUND: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. METHODS: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. DISCUSSION: The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov with identification number NCT05803473 on March 27th 2023.

Use of Intravenous Lipid Emulsion Therapy and Insulin in a Case of Tarka Intoxication.

INTRODUCTION: Tarka (trandolapril/verapamil hydrohloride extended-release) is a fixed-dose combination antihypertensive drug formed from verapamil hydrochloride and trandolapril. Toxicologic manifestations of Tarka overdose are altered mental status, bradycardia, hypotension, atrioventricular block (first-degree), hyperglycemia, metabolic acidosis, and shock. CASE PRESENTATION: We report a case of Tarka toxicity in a 2-year-old girl who presented with altered mental status, cardiogenic shock, hypotension, bradycardia, severe metabolic acidosis, hyperglycemia, and first-degree atrioventricular block. We started fluid resuscitation, epinephrine, norepinephrine, and insulin. Because of the patient's hyperlactatemia and hypotension despite standard therapies, we initiated intravenous lipid emulsion (ILE) therapy, after which her condition improved promptly. DISCUSSION: Tarka overdose may be life-threatening as it can cause cardiogenic shock. In our patient, the regression of lactate elevation in a short time with ILE therapy and the improvement of her general condition highlight the importance of ILE. CONCLUSIONS: ILE is an alternative treatment method for acute lipophilic drug intoxications, such as Tarka.

Risk of acute pancreatitis among new users of empagliflozin compared to sulfonylureas in patients with type 2 diabetes: A post-authorization safety study.

PURPOSE: This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin. METHODS: Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters. RESULTS: The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up. CONCLUSIONS: The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis.

[Features of type 2 diabetes mellitus and its pharmacotherapy in outpatients].

BACKGROUND: Type 2 diabetes mellitus (DM) remains the most common type of DM and is associat-ed with disabling complications, reduced quality of life and reduced life expectancy. Satisfactory control of carbohydrate metabolism remains the key way to manage them. AIM: To perform a retrospective analysis of carbohydrate metabolism (in terms of glycated hemoglobin - HbA1c), the prevalence of complications, and features of hypoglycemic and concomitant therapy in patients with type 2 DM. MATERIALS AND METHODS: The analysis of sex and age characteristics, achieved level of HbA1c, diabetes complications, sugar-reducing and concomitant therapy according to the data of outpatient records of the patients who are on dispensary registration with an endocrinologist in the Endocrinology Department of the Consultative and Diagnostic Polyclinic of the Tomsk Regional Clinical Hospital in Tomsk was carried out. RESULTS: 546 outpatient medical records of patients with type 2 DM were analysed, among which there were 39.6% men (n=216) with a history of type 2 DM 8.0 years [3.0; 13.0] , median age 64.0 years [54.5; 71.0] and 60.4% women (n=330), history of type 2 DM 10.0 years [5.0; 15.0], median age 70.0 years [63.0; 75.0]. The achieved HbA1c level in men was 7.6% [6.3; 9.0] and in women 7.4% [6.4; 9.1]. 19.4% of men and 13.6% of women had an aggravated history of type 2 DM. According to the history, 6.5% of men (n=14) and 3% of women (n=10) with type 2 DM had a history of stroke, and myocardial infarction 12% (n=26) and 1.5% (n=5), respectively. Among the analysed outpatient records of type 2 DM patients, 18.5% of men (n=40) and 12.4% of women (n=41) were found to have diabetic nephropathy. Diabetic retinopathy was reported in 9.3% (n=20) of men and 4.2% (n=14) of women. Diabetic macroangiopathies were detected in 29.6% (n=64) of males and 9.7% (n=32) of females. Among other chronic complications of DM, diabetic neuroosteoarthropathy was recorded in 1% (n=2) of males and 3% (n=10) of females, diabetic polyneuropathy in 25% (n=54) and 21.5% (n=71), respectively. Diabetic foot was diagnosed in 1.9% (n=4) of men and 1.8% (n=6) of women. Among comorbid pathology, obesity was diagnosed in 45.4% (n=88) of men and 69.1% (n=228) of women, dyslipidaemia in 10.2% (n=22) and 10.6% (n=35) respectively, hypertension in 39.8% (n=86) and 32.6% (n=108) of cases. The diagnosis of non-alcoholic fatty liver disease was verified in 3.7% of men (n=7) and 1.8% of women (n=6), chronic heart failure in 7.4% of men (n=16) and 2.4% of women (n=8) registered for type 2 DM. According to the analysed outpatient records, 4.1% (n=23) of patients received diet therapy, 48.3% (n=263) received monotherapy and 47.6% (n=260) received combination therapy for type 2 DM. Metformin was the most commonly used monotherapy for type 2 DM 36.1% (n=197), followed by insulin 6.9% (n=38), sulfonylurea derivatives - 2.7% (n=15). Combination of metformin and dipeptidyl peptidase-4 inhibitors (13.9%) was the most commonly used combination therapy. CONCLUSION: Analysis of the current situation in the diabetology service will help to identify weaknesses and strengths, which is necessary to optimise existing therapeutic approaches in accordance with current clinical recommendations.