Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.

Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Cinnamomi Cortex Regulates Incretin Effect in Diabetic Rats / 中国实验方剂学杂志

ObjectiveTo observe the pharmacodynamic effects of Cinnamomi Cortex on the incretin effect in the rat model of diabetes mellites （DM） induced by streptozotocin （STZ） and explore the underlying mechanism from glucagon-like peptide-1 （GLP-1） and dipeptidyl peptidase-4 （DPP-4）. MethodForty SD rats were randomly assigned into blank， model， sitagliptin （0.1 g·kg-1）， and low- and high-dose Cinnamomi Cortex （0.45 and 0.9 g·kg-1， respectively） groups. The DM rat model was established by a high-fat diet combined with intraperitoneal injection of 40 mg·kg-1 STZ in other groups except the blank group. The intervention lasted for 8 weeks. The status， body weight， water intake， food intake， and fasting blood glucose （FBG） of the rats were observed and determined. Hematoxylin-eosin staining was employed to reveal the pathological changes of the pancreas， and immunohistochemistry to detect the expression of glucagon in the pancreas. Biochemical assay was employed to measure the serum levels of lipid metabolism indexes such as total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL）. Enzyme-linked immunosorbent assay was employed to determine the levels of glycosylated hemoglobin， insulin， glucagon， GLP-1， and glucose-dependent insulinotropic polypeptide （GIP） in rat serum， and Western blot to determine the protein levels of GLP-1 and DPP-4 in the pancreas. ResultAfter 8 weeks of intervention， the model group showed higher body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and lower HDL， GLP-1， and GIP than the blank group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed lower body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and higher HDL， GLP-1， and GIP than the model group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed recovered morphology of islet cells and no nucleus aggregation. Compared with the model group， the Cinnamomi Cortex groups showed declined levels of glucagon in the center of islet cells. Compared with the blank group， the model group showed up-regulated protein level of DPP-4 and down-regulated protein level of GLP-1 （P<0.01）. Compared with the model group， the high-dose Cinnamomi Cortex groups showed down-regulated protein level of DPP-4 and up-regulated protein level of GLP-1 （P<0.05）. ConclusionCinnamomi Cortex may reduce blood glucose and improve incretin effect to lower the blood glucose level by regulating DPP-4 and GLP-1 in DM rats.

Association between sitagliptin plus vitamin D3 (VIDPP-4i) use and clinical remission in patients with new-onset type 1 diabetes: a retrospective case-control study

ABSTRACT Objective: The occurrence of partial remission (honeymoon phase) in type 1 diabetes (T1D) has been associated with a reduced risk of chronic microvascular complications of diabetes. We have published case reports showing that a combination therapy with the DPP-4 inhibitor sitagliptin plus vitamin D3 (VIDPP-4i) can prolong the honeymoon phase in patients with new-onset T1D. In the present case-control study, we investigated the frequency of occurrence of clinical remission (CR) in patients with new-onset T1D after VIDPP-4i treatment. Subjects and methods: In this case-control study, we collected data spanning 10 years from medical records of 46 patients (23 females) recently diagnosed with T1D. Overall, 27 participants with CR (insulin dose-adjusted glycated hemoglobin [IDAA1c] ≤ 9) at 12 or 24 months composed the case group, and 19 participants without CR served as the control group. Chi-square with Yates correction was used to analyze the association between VIDPP-4i use and CR, and odds ratio (OR) was used to determine the chance of CR due to VIDPP-4i treatment exposure. Results: In all, 37 patients (80.4%) experienced CR at some time over 24 months. The mean CR duration was 13.15 ± 9.91 months. Treatment with VIDPP-4i was significantly associated with CR. At 24 months, the OR of CR after VIDPP-4i exposure was 9.0 (95% confidence interval [CI] 2.21-30.18, p = 0.0036). Additionally, 9 (33.6%) and 4 (14.8%) patients in the VIDPP-4i group experienced insulin-free CR at 12 and 24 months, respectively. Conclusion: Therapy with VIDPP-4i was associated with a higher frequency and duration of the honeymoon phase. Randomized controlled trials are needed to confirm these findings.

Bullous Drug Reaction with Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

Hypoglycemic drugs in the dipeptidyl peptidase-4 (DPP-4) inhibitor class are used as a second-line treatment for type 2 diabetes mellitus. With DPP-4 inhibitors, there have been a few reports of cutaneous side effects such as bullous response, fixed drug eruption, and photosensitivity. There is no definitive pathophysiology for the above mentioned allergic reactions. Sitagliptin phosphate belongs to the DPP-4 inhibitor class. This is a case report of a sitagliptin-induced bullous drug reaction manifesting three weeks after starting therapy. He had bullous pemphigoid-like eruptions all over the body. The patient showed improvement once sitagliptin was discontinued alon with oral and topical steroid treatment.

A Single-Center, Observational, Retrospective Cost-Effective Analysis of Treating Inadequately Controlled Type 2 Diabetes Mellitus by Addition of DPP4 Inhibitors Versus Intensified Treatment with Conventional Drugs

Objective: To compare the cost effectiveness and achievement of glycemic goals in patients inadequately controlled by conventional drugs receiving either intensified treatment or DPP4 inhibitor as an add on. It shall help us to identify a preferred choice of treatment. Materials and Methods: As per study protocol, 52 patients with inadequately controlled type 2 diabetes mellitus (DM) were included in the study. They received either intensified treatment or add-on with DPP4 inhibitor. Glycated hemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), adverse drug reactions, and their cost were calculated for the next 6 months of therapy. Results: Add on therapy with DPP4 inhibitor showed a greater achievement of glycemic goals. Target HbA1c was achieved by 58.6% (P < 0.0001) versus 40% (P < 0.05), FBS was achieved by 78.50% (P < 0.0001) versus 50% (P < 0.16), and PPBS was achieved by 63.6% (P < 0.0001) versus 42.8% (P < 0.03) in the add-on with DPP4 inhibitor versus intensified treatment group. No hypoglycemic episodes were documented in both the groups. Add-on with DPP4 inhibitor cost (×5.13) as compared to intensified treatment. Conclusions: Add-on with DPP4 inhibitor therapy achieved glycemic goals in greater proportion of patients as compared to treatment intensification but at 5 times the cost of therapy. Since the patent restrictions for DPP4 inhibitors such as vildagliptin and teneligliptin are over, the cost of therapy has come down. Hence their benefits should be extended to a greater proportion of patients with inadequately controlled type 2 DM.

Terapias naturales para la reducción de complicaciones en pacientes con diabetes tipo 2 y COVID-19 / Natural therapies for the reduction of complications in patients with type 2 diabetes and COVID-19

Background: In December 2019, a series of cases occurred in Wuhan (China), caused by a new coronavirus. On March 11, 2020, the WHO declared the COVID-19 disease, caused by SARS-CoV-2, as a pandemic. In Peru, the first person infected with SARS-CoV-2 was confirmed on March 6, 2020. The number of infected has been constantly increasing to this day. Purpose: It is relevant to the current pandemic, understanding the mechanism of infection of SARS-CoV-2 in diabetic patients and in this way to be able to provide natural alternatives to reduce the complications that these patients can carry out until death. Methodology: An information search was carried out between April 6 and August 25 of 2020 in databases and indexed journals, whose articles have been published between 2011 and 2020. Results: It was found regarding inhibitors of dipeptidyl peptidase (DPP-4) evaluated in in vitro tests, that the Berberis aristata species has a metabolite called "berberine", which has the highest inhibitory capacity among the mentioned species, and, concerning furine inhibition, among the in vitro tests, catechin has a significant inhibitory capacity; it also has DPP-4 inhibitory activity. Conclusion: There is a great variety of medicinal plants with inhibitory properties for DPP-4 and some for furin. These properties are beneficial in patients with type 2 diabetes, since they reduce the activity of these proteases and, consequently, the complications in SARS-CoV-2 infection

Antecedentes: En diciembre de 2019, se registraron una serie de casos producidos por un nuevo coronavirus en Wuhan (China). El 11 de marzo de 2020, la Organización Mundial de la Salud declaró a la COVID-19, provocada por el coronavirus 2 causante del síndrome respiratorio agudo grave (SARS-CoV-2), como una pandemia. En el Perú, la primera persona infectada por SARS-CoV-2 fue confirmada el 6 de marzo de 2020; desde entonces, la cifra de infectados ha ido en constante aumento hasta el día de hoy. Propósito: Es relevante, ante la actual pandemia, entender el mecanismo de infección del SARS-CoV-2 en pacientes diabéticos, para, de esta manera, poder dar alternativas naturales para disminuir las complicaciones que pueden llevar a estos pacientes hasta la muerte. Metodología: se realizó una búsqueda de información entre el 6 de abril y el 25 de agosto de 2020, en bases de datos y revistas indexadas, cuyos artículos han sido publicados entre 2011 y 2020. Resultados: Se encontró, en cuanto a los inhibidores de la dipeptidilpeptidasa 4 (DPP-4) evaluados en ensayos in vitro, que la especie Berberis aristata posee un metabolito denominado "berberina", el cual presentó la mayor capacidad inhibitoria entre las especies analizadas. Con respecto a la inhibición de la furina, en los ensayos in vitro, la catequina posee una capacidad inhibitoria significativa; además de actividad inhibitoria para la DPP-4. Conclusión: Existe una gran variedad de plantas medicinales con propiedades inhibitorias para la DPP-4, y algunas de ellas para la furina. Estas propiedades son beneficiosas en pacientes con diabetes tipo 2, dado que reducen la actividad de estas proteasas y, por consiguiente, las complicaciones causadas por la infección por SARS-CoV-2

SUV39H1 deficiency suppresses clear cell renal cell carcinoma growth by inducing ferroptosis

Clear cell renal cell carcinoma (ccRCC) is a common kidney malignancy characterized by a poor prognosis. Suppressor of variegation 3-9 homolog 1 (

Inhibition of Metformin Combined with Cisplatin on Proliferation of Human Osteosarcoma MG-63 Cells / 中国生物化学与分子生物学报

In order to study the effect and its potential mechanism of metformin combined with cisplatin treatment on human osteosarcoma MG-63 cells, MG-63 cells were treated with metformin and cisplatin and the cell proliferation and apoptosis were detected using CCK8 and flow cytometry; Cell clone formation experiment was performed to detect clone formation rate in each group; Trans well experiment was used to detect the migration and invasion ability of osteosarcoma MG-63 cells, and qPCR and Western blot were used to detect the expression of RNA and protein of apoptosis-related genes. The results showed that metformin combined with cisplatin inhibited the proliferation of human osteosarcoma MG-63 cells and promoted their apoptosis significantly (P < 0. 01); Metformin combined with cisplatin inhibited the clone formation (P < 0. 01), and the migration and invasion of human osteosarcoma MG-63 cells (P < 0. 01); Furthermore, metformin combined with cisplatin down-regulated the expression of apoptosis-related genes MCl￣1and XIAP (P <0. 01), but up-regulated the expression of apoptosis-related genes CASPASE￣3 and Cyto C (P <0. 01) and migration and invasion related genes MMP￣2 and MMP￣9 (P <0. 01). Our study indicated that metformin combined with cisplatin inhibited proliferation, promoted cell apoptosis through MCl￣1 and XIAP, and inhibited cell migration and invasion by regulating the MMP￣2 and MMP￣9 pathways in human osteosarcoma MG-63 cells.

Investigation of canine visceral leishmaniasis in a non-endemic area in Brazil and the comparison of serological and molecular diagnostic tests

Abstract INTRODUCTION: Visceral leishmaniasis (VL) is an important zoonosis in Brazil. Previous identification of parasitized dogs can also help prevent the disease in humans, even in non-endemic areas of the country. The Brazilian Ministry of Health recommends diagnosis in dogs using a DPP® (rapid test) as a screening test and an immunoenzymatic assay (ELISA) as a confirmatory test (DPP®+ELISA), and culling infected dogs as a legal control measure. However, the accuracy of these serological tests has been questioned. METHODS: VL in dogs was investigated in a non-endemic area of the São Paulo state for three consecutive years, and the performances of different diagnostic tests were compared. RESULTS: A total of 331 dog samples were collected in 2015, 373 in 2016, and 347 in 2017. The seroprevalence by DPP®+ELISA was 3.3, 3.2, and 0.3%, respectively, and by indirect immunofluorescence assay (IFA), it was 3.0, 5.6, and 5.5%, respectively. ELISA confirmed 18.4% of DPP® positive samples. The concordance between the IFA and DPP® was 83.9%. The concordance between IFA and DPP®+ELISA was 92.9%. A molecular diagnostic test (PCR) was performed in 63.2% of the seropositive samples, all of which were negative. CONCLUSIONS: In non-endemic areas, diagnostic tests in dogs should be carefully evaluated to avoid false results.

Date Palm Pollen Grains as a Potential Manager for Male Sub-fertility: A Clinical Trial

Medicinal plants are identified and used throughout human history; it has a great economic value especially in drugs discovery. Date palm pollen (DPP) is used traditionally in Sudan for treating sub-fertile male patients. Male infertility is heterogeneous group of disorders, most of them are idiopathic. This study is aimed to investigate the role of pharmaceutical preparation of DPP in amelioration of male sub fertility with detection of any possible adverse effects on the major body system functions, through blood picture, liver enzymes and kidney function. This study is a single group pretest-posttest experimental prospective comparative self-control. Sub-fertile men with Idiopathic oligoasthenozoospermia or azoospermia were received 500 mg capsules of DPP twice daily for three months after conducting their safety profiles to detect any toxic effects on hematological, hepatological and nephrological functions, Blood samples were taken from the patients for serum level of FSH (for azoospermic patients), FSH and Testosterone (for oligoasthenozoospermic patients). Finally, Semen sample have been obtained for computerized assisted semen analysis (CASA) report I and II. DPP administration induced significant increase (p≤0.001) in testosterone level (in oligoasthenozoospermic patients) and FSH level (in azoospermic patients). DPP induced significant changes (p≤0.001) towards improvement in the total and progressive sperm motility percentages measured in oligoasthenozoospermic patients by CASA dynamic analysis report I and II. The toxicological studies for DPP approved their safety use in human

Pharmacological evaluation of Rhazya stricta root extract / Evaluación farmacológica del extracto de raíz de Rhazya stricta

The present study aimed to screen the Rhazya stricta Decne root for its antihyperglycemic and antioxidants potential through invitro assays along with phytochemical and elemental analyses. The crude extract was prepared through maceration and fractionated using solvent-solvent extraction technique. The spectroscopic studies indicated the presence of various phytochemical classes in the extract and its fractions. The antioxidant assays showed notable results along with a good concentration of phenolic and flavonoid contents. Enzyme inhibition assays demonstrated glucose-lowering effects by inhibiting the enzyme activity which could reduce post-prandial blood glucose level. The Dipeptidyl peptidase-IV (DPP-IV) inhibition assay results showed the novel DPP-IV inhibition activity of the plant extract and all fractions showed noteworthy enzyme inhibition and antihyperglycemic activity. Conclusively, the Rhazya stricta root extract displayed its antioxidant and antihyperglycemic potential due to the presence of various classes of phytochemicals and micro-nutrients.

El presente estudio tuvo como objetivo examinar la raíz de Rhazya stricta Decne por su potencial antihiperglicémico y antioxidante a través de ensayos in vitro junto con análisis fitoquímicos y elementales. El extracto crudo se preparó por maceración y se fraccionó usando una técnica de extracción solvente-solvente. Los estudios espectroscópicos indicaron la presencia de varias clases fitoquímicas en el extracto y sus fracciones. Los ensayos antioxidantes mostraron resultados notables junto con una importante concentración de contenido fenólico y flavonoide. Los ensayos de inhibición enzimática demostraron efectos reductores de la glucosa al inhibir la actividad enzimática que podría reducir el nivel de glucosa posprandial en sangre. Los resultados del ensayo de inhibición de Dipeptidyl peptidase-IV (DPP-IV) mostraron la nueva actividad de inhibición de DPP-IV del extracto de la planta y todas las fracciones mostraron una notable inhibición enzimática y actividad antihiperglicémica. En conclusión, el extracto de raíz de Rhazya stricta Decne mostró su potencial antioxidante y antihiperglicémico debido a la presencia de varias clases de fitoquímicos y micronutrientes.

Chemical constituents and hypoglycemic activity of Phlomis tuberosa / 中草药

Objective: To study the chemical constituents and hypoglycemic activity of Phlomis tuberosa. Methods: The db/db diabetic mice was used to screen the hypoglycemic active site of P. tuberosa. The chemical constituents were isolated and purified by various separation and analysis techniques. The structures of these compounds were identified by spectroscopic analysis (1H-, 13C-NMR and MS). The hypoglycemic activities of these compounds were verified by the DPP-4 inhibitory activity in vitro. Results: Ethyl acetate extract of P. tuberosa showed significant hypoglycemic effect. Twenty-five compounds were isolated from the active site, containing β-stiosterol (1), stigmasterol (2), daucosterol (3), clerosterol-stigmast-4-ene-3,6-dione (4), 22-dehydro- stigmast-4-ene-3,6-dione (5), ellagic acid (6), ethyl gallate (7), gllagic acid (8), 4-hydroxybenzoic acid (9), 3,4-diohydroxybenzoic acid (10), cinnamic acid (11), p-hydroxy-cinnamic acid (12), caffeic acid (13), 5-hydromethylfuraldehyde (14), quinic acid (15), chlorogenic acid (16), ferulic (17), 2,3-dimethoxy-5-methyl-6-(3,7,11,15,19-pentamethyl-2,6,10,14,18-eicosapentaen-1- yl)-2,5-cyclohexadiene-1,4-dione (18), 1-O-caffeoyl- quinic acid (19), 3,5-dimethoxy-4-hydroxy-benzene carbonic-1-O-β-D-glucoside (20), 2-O-butyl-α-D-fructofuranoside (21), n-octadecanoic acid (22), stearic acid (23), methyl-5-(hydroxymethyl) furan-2-carboxylate (24) and 4-hydroxy-3-methoxy-benzaldehyde(25). Nine compounds were obtained from the genus Phlomis for the first time, in which ellagic acid (6), quinic acid (15), and 1-O- caffeoylquinic acid (19) showed strong DPP-4 inhibitory activity with IC50 of 72.3, 89.2, and 103.4 μmol/L, respectively. The IC50 of the positive drug diprotin A was 50 μmol/L. Conclusion: Compounds (3-7 and 18-21) are obtained from the genus Phlomis for the first time. Compound 6, 15, and 19 show DPP-4 inhibitory activities.

Synthesis and synthetic process optimization of a specific dipeptidyl peptidase-Ⅳinhibitor vildagliptin / 国际药学研究杂志

Objective: To investigate and optimize the synthetic process of specific dipeptidyl peptidase-Ⅳ(DPP-Ⅳ)inhibitor vitagliptin. Methods: The aimed synthetic route was conceived by the literature survey according to the advantages and disadvantages of the reported synthetic routes. The key process parameters were determined by the orthogonal test or single factor test for the main intermediates in the speed limiting step. Results: The structures of intermediates and target compound were confirmed by MS and 1H NMR data. The overall yield of the target compound was 38.5%. Conclusion: The synthetic process has the advantages of lower cost, simple operation and mild reaction condition, and the yield has been improved by optimizing the crystallization solvent, which should be more suitable for industrial production.

Isolation and identification of unknown impurities of alogliptin benzoate / 中国药科大学学报

@#By silica gel column chromatography, solvent extraction and preparative high performance liquid chromatography (HPLC), four new related substance were isolated and purified from the mass production and preparation process of alogliptin benzoate. Then it was analyzed and confirmed by various spectrum identification methods such as nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS) and Fourier-transform infrared spectroscopy (FTIR) according to its physical and chemical properties. The chemical structures of the four related substances produced in each step of the synthesis process of alogliptin benzoate were determined, and they were named as impurities L, M, T, and V. These four related substances were new impurities which were found for the first time. The isolation and identification of these impurities are of great importance to the quality control of alogliptin benzoate, and the optimization of manufacturing process.

The observational, cross-sectional study of drug utilization 90% and use of dipeptidyl peptidase-4 inhibitor in the patients with type 2 diabetes mellitus

Background: Diabetes is a chronic metabolic disease which affects the quality of life. It leads to multiple complications due to metabolic involvement. Out of multiple drugs used to treat diabetes, dipeptidyl peptidase 4 (DPP-4) inhibitors are comparatively new drugs used for type-2-diabetes mellitus (DM) treatment. This study aimed to find out the drug utilization (DU) 90% and use of DPP-4 inhibitors in patients with type-2-DM.Methods: A prospective, cross-sectional, observational study was conducted at a private healthcare clinic of an endocrinologist in Nashik. Type-2-DM patients of both sexes were selected and a total of 199 patients were enrolled in the study. The consented patients were interviewed and prescription copies were collected. After studying them; statistical analysis was done and results and conclusions were drawn.Results: Out of total prescribed drugs, 58.77% of drugs were anti-diabetics. It was observed that the biguanides were most frequently (25.32%) prescribed while the least prescribed drugs were meglitinide analogues (0.08%). Most commonly utilized anti-diabetic found to be metformin. Vildagliptin 50 mg is the most commonly prescribed drug from DPP-4 inhibitors. Most of the drugs from the DPP-4 inhibitor group came under DU90%.Conclusions:DPP-4 inhibitors are showing wide acceptability by endocrinologists for type-2-DM management, according to this study. Performing repetitive drug utilization pattern study and circulation of standard treatment guidelines to practising physicians can be required. To emphasize the point on generic prescription, more awareness should be created. So that these can responses to further cost-effective and rational prescribing practices.

A study to assess clinical profile of Indian type 2 diabetes mellitus patients treated with Teneligliptin-ASPIRE study

Background: Teneligliptin is a DPP-4 inhibitor with unique chemical structure. Efficacy and safety of Teneligliptin is well established in the patients with type 2 diabetes mellitus (T2DM) in different randomized controlled trials. However, limited real-world data is available for Teneligliptin pertaining to Indian T2DM patient profile such as demographics, duration of disease, currently prescribed anti-hyperglycemic drugs, initiation of Teneligliptin as monotherapy or as an add on therapy.Methods: A cross-sectional, multicenter, non-interventional study was conducted to understand the demographics and clinical profile of Indian T2DM patients (n=5091) who were prescribed Teneligliptin.Results: Majority of patients were male (65.2%) with family history of T2DM present in 43.45% of cases. Age at onset of T2DM was 51.1±11.6 years. Among the T2DM patients, 36.2% of patients were newly diagnosed and more than half of them (54.7%) were uncontrolled with current anti-hyperglycemic drugs. Mean HbA1c level among these patients was 8.09±1.3%. Mean fasting and postprandial blood glucose levels were 170.2±46.9 mg/dl and 255.3±69.3 mg/dl respectively. Teneligliptin was prescribed as monotherapy in 2165 (41.66 %) of patients while as dual, triple and quadruple therapy in 2346 (46.08%) and 551 (10.82%) and 29 (0.56%) respectively. Among the patients on current anti-hyperglycemic treatment, most commonly prescribed drugs along with Teneligliptin were metformin (43.39%) followed by glimepiride (11%) and voglibose (3.42%).Conclusions: Teneligliptin is preferred as monotherapy and combination with metformin and sulfonylureas (mostly glimepiride) in newly diagnosed and uncontrolled T2DM patients in Indian scenario.

Effect of Sitagliptin on Diabetic Profile of Type 2 Diabetes Mellitus Patients

Introduction: Time since death is an important topic that playsmajor role in forensic medicine. The accurate determinationof time since death is found to be helpful in medico legalinvestigation. Advancements in the methods for estimatingtime since death have enabled us to determine post-morteminterval more precisely. Since the 1850s, scientists have beenworking on different methods to determine post-morteminterval. Hence, the aim of the present study was to assess thetime since death using method of rigor mortis in the autopsiesdone at the mortuary of Osmania General Hospital.Materials and Methods: About 500 medico-legal autopsieswere selected where the exact time of death was known andthe body had been kept at prevailing room temperature. Agood quality digital hygrometer was used to note the dailyreadings of temperature and humidity. Presence or absence ofrigor mortis and its extent was noticed in both voluntary andinvoluntary muscles.Results: More unnatural deaths are in suspiciouscircumstances are occurring in males when compared tofemales. The average duration for onset of rigor mortis was 8hours and 39 minutes. The minimum duration in which rigormortis had begun to appear in the body was 1 hour and 35minutes while the longest maximum by which rigor mortishad not completely appeared in the body was 24 hours.Conclusion: Rigor mortis has been used for assessment oftime since death from long time. It is considered to be themost important and interesting method to estimate the timesince death.

Terapia complementaria a la insulina en el tratamiento de niños y adolescentes con diabetes mellitus tipo 1- (DM1) / Therapies complementaries to insulin in the treatment of children and adolescents with type 1 diabetes mellitus (T1DM)

La diabetes mellitus tipo 1 (DM1), es una enfermedad crónica caracterizada por la deficiencia de insulina debido a la pérdida de células ß pancreáticas, las alteraciones hormonales en la DM 1 no se limitan a la deficiencia de insulina; existiendo también secreción inadecuadada de glucagón en el período postprandial. Aunque el control glucémico con terapias intensivas con insulina ha reducido la incidencia de complicaciones microvascular y macrovasculares. La mayoría de las personas con DM1 tienen un control glucémico subóptimo; Por lo tanto, el uso de farmacoterapia adyuvante para mejorar el control ha sido de interés clínico. El uso de estos nuevos medicamentos brindaría la oportunidad de imitar más de cerca la fisiología pancreática normal, y contrarrestar otros mecanismos fisiopatológicos diferentes a Insulinopenia; contribuyendo a lograr un mejor control metabólico y expectativa de vida.

Type 1 diabetes mellitus (T1DM), is a chronic disease characterized by insulin deficiency due to the loss of pancreatic ß cells, the hormonal alterations in T1DM are not limited to insulin deficiency; there is also a deregulated glucagon secretion in the postprandial period. Although glycemic control with intensive therapies with insulin has reduced the incidence of microvascular and macrovascular complications, most people with T1DM1 glycemic control; therefore, the use of adjuvant pharmacotherapy to improve control has been of clinical interest. The use of these new drugs would offer the opportunity to imitate more closely the normal pancreatic physiology, and to counteract other physiopathological mechanisms different from insulinopenia; contributing to achieve better metabolic control and life expectancy.

DPP-4 inhibitory activity and myocardial salvaging effects of Commiphora mukul in experimental diabetes

Background: Commiphora mukul (Burseraceae) is commonly known as Guggul in Ayurveda. Several studies have reported antidiabetic activity of Commiphora mukul but there are no studies to explore the DPP-4 inhibitory activity and myocardial salvaging effects of Commiphora mukul in setting of diabetes mellitus. The present study was designed to evaluate the cardioprotective efficacy as well as safety of the medicinal plant Commiphora mukul (Guggul) in the experimental model of myocardial infarction co-existing with diabetes.Methods: Diabetes was induced with single dose of streptozotocin (STZ): 45mg/kg ip and myocardial infarction was produced by administering isoproterenol (ISP): (85mg/kg, sc) to rats 24 and 48 h prior to scarification (5th week). After the confirmation of diabetes on 7th day (glucose>200mg/dl), vildagliptin (10 mg/kg) and Commiphora mukul (200 mg/kg) were administered orally from 1st to 5th week (4 weeks). At the end of experimental period, normal control, diabetic-isoproterenol control, vildagliptin and Commiphora mukul group rats were sacrificed for further biochemical investigations as well as histopathological evaluation.Results: Commiphora mukul treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB serum DPP-4, hs-CRP levels as compared to diabetic ISP control group. In addition, Commiphora mukul showed significant cardioprotection as indicated by positive correlation between cardiac marker CPK-MB and serum DPP-4. The histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Commiphora mukul. In addition, Commiphora mukul was found to be safe to the liver and kidney.Conclusions: The natural DPP-4 inhibitor Commiphora mukul demonstrated significant cardioprotective effects in experimental model of myocardial infarction co-existing with diabetes.