Critical Appraisal of Journel Article

By Dr Ketan Asawalle

Efficacy and safety of add on therapy

of bromocriptine with metformin in

Indian patients with type 2 diabetes

mellitus: A randomized open labeled

phase IV clinical trial

Arijit Ghosh, Nilanjan Sengupta1, Pranab Sahana1, Debasis Giri1, Parama Sengupta, Nina DasIndian Journal of Pharmacology | February 2014 | Vol 46 | Issue 1

Introduction

Type 2 Diabetes Mellitus is caused mainly due to insensitivity of target organs of Insulin

Metformin is the 1st agent added to diet modification and exercise according to current trends

Due to need of regular dosage ORAL therapy is most convenient for patients

But due to safety issues, tolerability and weight change of patient, there is need of new

Bromocriptine got FDA approval in 2009 as an adjuvant for treatment of type 2 DM. (4)

Bromocriptine is a DOPAMINE AGONIST acting centrally on D2 receptors to reduce blood glucose levels

Site of Action HYPOTHALLAMUS

OBJECTIVE

The present study was planned to compare effectiveness and safety of add on therapy of bromocriptine with metformin in Indian

METHODOLOGYTYPE OF STUDY

PROSPECTIVE

RANDOMISED

OPEN LABLED

PHASE IV

CLINICAL TRIAL

Ethics committee approval taken and trial registered in Clinical Trials Registry of India

SAMPLE SIZE CALCULATION

Based on an effect size of one, standard deviation of one, significance level α of 0.05 and power of the study as 80%, the ta

INCLUSION CRITERIA

Newly Diagnosed

18 TO 60 years

Type 2 DM

HbA1c >/= 6.5 </=10

EXCLUSION CRITERIA

Pregnanat/Lactating women

FPG>250mg/dl

PPPG>350mg/dl

comorbid cardiac renal conditions

allergy to drug

Based on selection criteria the patients were divided into 3 groups randomly

GROUP A - Metformin 500mg BD

GROUP B - Metformin 500mg BD + Bromocriptine 0.8mg

GROUP C - Metformin 500mg BD + Bromocriptine 1.6mg

Compliance assessed on basis of pill count method at every visit

Clinical (body weight) and biochemical (FPG, PPPG) evaluation was done at baseline (day 0) and at subsequent follow-up visits on weeks 4, 8, and 12. HbA

All patients were advised to stop smoking and consumption of alcohol during the study period.

DATA ANALYSIS

Subjects reporting for at least one post- baseline follow-up visit were analysed

Data were analyzed by repeated measures analysis of variance (ANOVA) paired t test and Chi square test

P value < 0.05 was considered to be statistically significant.

RESULTSSCREENED = 80

ENROLLED = 74

GROUP A = 23

GROUP B = 25

GROUP C = 26

. The most common AEs are nausea and vomiting. None of the patients in group A reported any AE. Three patients (12%) in group B reported nausea and vomiting. Six patients (23%) in group C reported dizziness and vomiting.

No statistically significant difference in base line levels of HbA1c

HbA1c values significantly reduced in all 3 groups from baseline levels

Intergroup analysis of data show at every interval (weeks 4, 8, and 12) add on therapy of bromocriptine with metformin compar

cont…

Intergroup analysis did not show any statistically significant change in weight of study subjects at different intervals

Changes in glycosylated hemoglobin (HbA1C) level (%) in groups A, B, and C

DISCUSSION

1. Despite availability of several oral ADAs, pharmacotherapy of type 2 DM is far from satisfactory. Hence, there is always n

2. Bromocriptine is a dopamine type 2 (D2)-receptor agonist that has been approved for the treatment of type 2 DM.

There are few clinical trials evaluated efficacy and safety of bromocriptine in type 2 DM

In a small study of 12 nondiabetic obese hyperinsulinemic (≥20 μU/mL) subjects, bromocriptine (1.6 mg/day for 2 weeks) reduced the fasting and postprandial (standardized meals) glucose levels without change in body weight.

controlled trial in which bromocriptine was added to therapy in poorly controlled (HbA

In type 2 diabetic subjects who completed 24 weeks of treatment and who took ≥80% of their medication, the placebo-subtracted decrease in HbA

CONCLUSION

labeled phase IV clinical trial showed that add on therapy of bromocriptine with metformin is more effective compared with metformin alone in a dose

Acknowledgment

The authors would like to thank Lupin Diabetes Care Ltd, Mumbai, Maharashtra, India for providing gift samples of study medic

EVALUATION

QUESTIONS TO ASK WHEN CRITICALLY APPRAISING A RESEARCH ARTICLE

1. Is the study question relevant?

2. Does the study add anything new?

3. What type of research question is being asked?

4. Was the study design appropriate for the research question?

5. Did the study design address the most important potential source of bias?

6. Was the study performed according to original protocol?

7. Does the study test the stated hypothesis?

8. Were the statistical analysis performed correctly?

9. Do the data justify the conclusions?

10.Are there any conflicts of interest?

1. Are the objectives clearly and precisely stated

Yes

2. Does the design meets the objectives?

Yes, to some extent.

3. Is the study based on a sample? Is it representative sample from the target population?

yes yes

4. If the study is an experiment, is there randomization and is the randomization procedure

explained?

yes

5. Does the sample size provide for possible non-response and, if it is follow-up study, drops out?

yes

6. Is the overall methodology adequate for achieving the objectives of the study?

Yes, but they have not mentioned about phase I to IV

7. Is the methodology ethically sound?

yes

8. Are the findings stated clearly and concisely, yet in sufficient detail for the readers to make their own judgment?

partial, weight information not mentioned

9. Are the conclusions based on facts, with the opinions clearly indicated as such?

yes, to some extent

10. Is the analysis focused on the objectives initially set out? Are coincidental findings specified?

yes11. Are the results consequent to the analysis presented?

yes, but not for all

12. Is a proper explanation given for the results obtained?

Yes, but not for all.

13. Do these conclusions really answer the questions posed in the objectives?

14. Is it clearly stated how the results of the investigation advance the current knowledge on the topic?

no