Journal Reporting

Dr. Pravinkumar Wahane

JR II, Dept. of Pharmacology

BJGMC, Pune

Michaela Diamant, Luc Van Gaal, Stephen Stranks, Justin Northrup, Dachuang Cao, Kristin Taylor,

Michael Trautmann

Lancet 2010; 375: 2234–43

Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomized trial

Introduction Management of diabetes:

Symptomatic glucocentric approach

Targeting pathophysiological principles, blood-glucose lowering, reduce bodyweight

Treatments needed that are

Convenient

Control both fasting & postprandial glucose level,

Reduce risk of hypoglycemia,

Avoid counterproductive side-effects

Introduction GLP-1) receptor agonists – exenatide controls both

fasting and postprandial glucose with weight loss & low risk of hypoglycemia

Once weekly formulation of exenatide developed,- goal of sustained glycaemic control alongside increased convenience of standard once-a week dosing

Associated with HbA1c reduction, weight loss & low hypoglycemic risk in randomized clinical trials

Introduction Study aims to test hypothesis that improvement

in HbA1c concentration achieved with once-weekly exenatide is better than once a day insulin glargine titrated to glucose targets

Materials & Methods Phase 3 , Multicentre trial of 26 week duration

from May 2008 to May 2009 at 72 study sites across USA, EU, Russia, Australia, Korea, Taiwan & Mexico

Materials & Methods Inclusion Criteria Type II DM pts. 18 yrs & above with suboptimum

glycaemic control despite maximum tolerated doses of Metformin or combined Metformin and Sulphonylurea treatment for 3 months or longer

HbA1c Conc.- 7.0 – 11.0 %

BMI – 25-35 kg/m2

Stable body weight for 3 months or more

Materials & Methods Exclusion Criteria > 3 episodes of major hypoglycemia within 6

months of screening

Treatment with systemic glucocorticoids within 4 weeks of screening

Treatment > 2 weeks with Insulin, Thiazoledinediones, α glucosidase inhibitors, DPP 4 inhibitors within 3 months of screening

Prescription & Non prescription drugs weight loss drugs within 3 months of screening

Study Procedure Pt. assigned to once weekly Exenatide or once

daily insulin Glargine titrated to blood glusose lowering regimens by computer generated randomization sequence

1 st group – Subcut. Inj. Of 2 mg Exenatide once weekly for 26 weeks

2 nd Group – Insulin Glargine Starting from 10 IU to maintain BGL 4.0 to 5.5 mmol/L for 26 weeks

Pts. Contd. Their Metformin/ Metformin + Sulphonylurea dosing till week 26

Study Procedure Pt. on Met+ Sulphonylurea T/t with confirmed

Hypoglycemia – advised to reduce Sulphonylureas

Blood glucose profiles measured at : Before & 2 hrs. after morning, Midday, Evening meals, Bedtime & at 3 AM

A/E – Those occurring after Randomization or worsening during study

Safety End points:- Adverse events, clinical lab. Assesments, Vital signs & Hypoglycemia

Study Procedure

Primary Endpoints: Change in Hb1Ac at week 26 compared to

baseline

Secondary Endpoints: Pts. Achieving HbA1c < 7.0 % & < 6.5 %

Fasting Serum Glucose Concentration

Self Monitored Serum Glucose Concentration

Study Procedure

Study Procedure

Secondary Endpoints (contd): Body Weight

Fasting Serum lipid Concentration

Urinary Albumin – Creatinine Ratio

High Sensetivity C Reactive Protein

Statistical Analysis Data analysed a/c to intention to treat principle

Predefined subgroup analysis of groups based on Hb1Ac level

Categorical variables analyzed – Fisher test

Continuous variables analyzed – t- test

SAS (version 9.1) used for analysis of data

Results

Results

Results

Results

Results

Results

Discussion

Exenatide once weekly > insulin glargine titrated to target glucose level in reduction of HbA1c levels

Exenatide more effective in weight reduction

Insulin Glargine – Fasting Glucose levels

Exenatide - Postprandial Glucose levels

Hypoglycemic events more common in pts. Receiving Sulphonylurea & in Glargine group

Conclusion

Once weekly Exenatide is better than Insulin glargine titrated to glucose level in pts. for whom risk of hypoglycemia, weight gain and convenience are particular concerns

Comments

Clinical trial registration No. – mentioned

Title – gives an idea about the objective but not about the dosing pattern of Insulin glargine

Introduction – Background information and purpose of study mentioned

Materials and Methods - Ethical approval & informed consent has been obtained

Place of study, design , randomization method and inclusion/exclusion criteria mentioned

Comments

Source of Drug – Mentioned

Results – Statistical tests applied mentioned, appropriate tables and figures included

Discussion – Results not repeated, Relevant studies mentioned, Limitations of study mentioned

Conclusion – Gives possible future implication of study

Support and Conflict of Interest – Mentioned

A comparative study of the effect of clonidine and tramadol on post spinal anesthesia shivering

Shukla U, Malhotra T, Prabhakar T.

Ind J Anesth; Vol 55; Issue 3;242-6; May- June 2011

Introduction

Regional anesthesia – used for elective & emergency operations

Shivering – 40- 70 % pts. Undergoing surgery under regional anesthesia

Results in ↑ metabolic rate, ↑ O2 consumption, ↑ CO2 production, ventilation & cardiac output

Also causes – wound infection, surgical bleeding, lactic acidosis, ↑ IOP, Arterial hypoxemia

Introduction

It is thought to be due to peri-operative hypothermia d/t neuraxial anesthesia induced inhibition of thermoregulatory mechanism

Pharmacological and Non Pharmacological methods available to control shivering

Study aims to compare efficacy, potency & hemodynamic effects of Clonidine v/s Tramadol in shivering

Materials & Methods

Prospective double – blind randomized study

Ethics committee approval and written informed consent were obtained from pts.

Inclusion Criteria 80 ASA grade I pts of either sex aged 18- 40

years scheduled for elective abdominal/ orthopedic/ gynecological surgeries included

Materials & Methods

Exclusion Criteria Known hypersensitivity to clonidine & Tramadol

Known H/o alcohol or substance abuse

H/o hyperthyroidism, cardiovascular diseases, psychological disorders, severe diabetes or autonomic neuropathies

Materials & MethodsGroup C

40 pts

Clonidine 0.5 ug/kg IV

Group T

40 pts

Tramadol 0.5 mg/kg IV

Materials & Methods

Axillary temp. recorded before commencement of spinal anesthesia, then every 5 min from baseline for 1 hour & then every 15 min for rest of observation period

Grading of shivering (Wrench) Grade 1,2,3,4.

Time(min) of start of shivering after spinal anesth Time (min) of disappearance of shivering Response rate (min) after treatment

Materials & Methods

T/t with Clonidine/ Tramadol reconsidered if shivering not subsided by 15 min

Side effects recorded

Sedation score recorded (Filos)

Statistical Analysis

Student t test & Chi- square test applied for interpretation of results

P value < 0.05 was considered statistically significant

Statistical analysis done using computerized software

Results

Results

No statistically significant difference in heart rate, mean blood pressure, axillary temp . O2 saturation between two groups

Nausea, vomiting, diarrhea higher in Tramadol Group than in Clonidine group

Discussion

Zavaherforoush et. al found clonidine more effective than pathedine & fentanyl for treating post spinal anesthesia shivering in elective LSCS

Meracadante S et. al also found the same results

Conclusion: Clonidine offers better control over post spinal

anesthesia shivering & thermodynamics than Tramadol along with fewer side effects

Comments

Clinical Trial Registration No. – Not mentioned

Title - Gives idea about study objective, but not about the study design

Introduction - Background information along with purpose of study mentioned

Materials and Methods – Ethics Committee approval obtained, informed consent taken

Site of study – not mentioned

Comments

Study Design, Inclusion & Exclusion criteria mentioned

Source of drug, Method of randomization - not mentioned

Results- Statistical tests employed mentioned briefly, Name of Statistical Software used has not been mentioned

Discussion – Introduction & Results repeated, Limitations of study mentioned

Support & Conflict of Interest mentioned as NIL