Comparative study of efficacy and adverse drug reactions in

type 2 diabetic patients on monotherapy versus

combination therapy in a Tertiary Care Hospital
B Pharm Protocol
Submitted By

Mr. Joshi Pushkar Vasant Ms.Yasmin Dakhani

Ms.Gayatri Jaju Ms.Chanda Pawar

To,
Institutional Ethical Committee
B.V.V.S.H.S.K College of Pharmacy Bagalkote-587101, Karnataka, India

Under the Guidance of:

Dr. M.G.Keshannavar
Dr. Naveen Sardar
 Department of Pharmacy Practice,
B.V.V.S. H.S.K College of Pharmacy Bagalkote-587101,Karnatak,India

1. Introduction:

1.1 Background information :

Diabetes mellitus is the most predominant disease affecting more than 180 million people globally,

around 400 million people will have diabetes by 2030.[1] Asian countries contribute >60% of the

global diabetic population.[2]

Type 2 Diabetes Mellitus (T2DM) is a chronic progressive disorder characterized by insulin resistance

and relative insulin deficiency, requiring pharmacological intervention for effective glycemic

control. Monotherapy with agents like metformin is often initiated; however, combination therapy

may be necessary for achieving target glycemic goals. While combination therapy can improve

efficacy, it may increase the risk of adverse drug reactions (ADRs) due to polypharmacy. Evaluating

both efficacy and ADRs between monotherapy and combination therapy is crucial for optimizing

treatment outcomes in T2DM.

The present study is done to assess the efficacy and adverse drug reactions in monotherapy with that

of combination therapy, by comparing different classes of oral anti-diabetics in diabetes mellitus type

2 patients.

1.2 Statement of the Problem:

 Limited comparative data exists assessing the efficacy and ADR profiles of monotherapy versus

combination therapy in T2DM patients in real-world Indian settings, hindering clinicians in

evidence-based decision-making.

1.3 Rationale/Significance of the Study:

The study will provide insights into the comparative efficacy (HbA1c, FBS, PPBS) and ADR profiles

in T2DM patients on monotherapy versus combination therapy, aiding in treatment optimization and

improved patient safety.

2. Objectives

2.1 General Objective:

To compare the efficacy and adverse drug reactions in T2DM patients on monotherapy versus

combination therapy.

2.2 Specific Objectives:

- To evaluate and compare glycemic control (HbA1c, FBS, PPBS) in patients on monotherapy and

combination therapy.

- To determine the incidence, type, and severity of ADRs in both groups.

- To assess the preventability of ADRs and identify contributing factors

3. Review of Literature

1. Kalra et al., 2015 – Discussed ADR burden in combination therapy.

2. UKPDS Group, 1998 – Highlighted efficacy benefits with intensive therapy.

3. Holstein et al., 2010 – ADR-related hospitalizations in diabetic patients.

 4. ADA Guidelines, 2024 – Emphasis on efficacy while minimizing ADR risk.

5. ICMR Guidelines, 2023 – Region-specific management approaches.

4. Methodology

- Study Design: Prospective, comparative, observational study.

- Study Setting: Tertiary care teaching hospital.

- Duration: 3 months.

- Population: Adult T2DM patients on stable therapy for ≥3 months.

- Inclusion Criteria: T2DM, age 30-80, on monotherapy or combination therapy.

- Exclusion Criteria: Type 1 DM, pregnancy, terminal illness, psychiatric illness.

- Sample Size: 50 patients (25 monotherapy, 25 combination therapy).

- Data Collection: Structured interviews, lab parameters (HbA1c, FBS, PPBS), ADR

documentation, WHO-UMC, Hartwig’s scale.

- Procedure: Baseline and follow-up glycemic parameters, ADR monitoring, classification, and

causality assessment.

5. Data Analysis Plan

- Software: Excel.

- Descriptive statistics for demographics, efficacy, and ADR data.

- Inferential statistics: Paired/unpaired t-tests, Chi-square tests, logistic regression for ADR

predictors.

- Significance: p < 0.05, CI 95%.

6. Ethical Considerations
IEC approval, informed consent from participants, confidentiality maintenance, and voluntary

withdrawal ensured.

7. References

1. Kalra S, et al. Indian J Endocrinol Metab. 2015.

2. UKPDS Group. Lancet. 1998.

3. Holstein A, et al. Diabetes Care. 2010.

4. ADA Guidelines. 2024.

5. ICMR Guidelines. 2023.

6. WHO-UMC Causality Criteria.

7. Hartwig SC, et al. Am J Hosp Pharm. 1992.

8. Schumock GT, Thornton JP. Am J Hosp Pharm. 1992.

9.
Review of Study:

1. Fehmi M. Mukadam et.al.

Adverse Drug Reactions (ADRs) present significant challenges in healthcare, necessitating

vigilant monitoring and analysis to enhance medication safety protocols. This retrospective study

aimed to analyse ADRs reported at an Adverse Drug Reactions Monitoring Centre (AMC) to

understand prevalence, patterns, and characteristics of ADRs. Retrospective data from January to

December 2023 were collected from the AMC at Vaishampayan Memorial Medical College, Solapur.

A total of 282 ADR reports were analysed for frequency, severity, implicated medications, patient

demographics, and associated clinical factors. Causality assessment was performed using the WHO-

Uppsala Monitoring Centre scale The majority of ADRs were associated with the oral route of drug

administration (79.43%), and most were categorized as minor severity (68.44%) and probable

causality (91.84%). Common ADR symptoms included vomiting (9.55%) and rash (9.22%).

Antimicrobial agents were the most suspected drugs causing ADRs (17.38%). The study revealed
 discrepancies in ADR reporting patterns and highlighted the importance of pharmacovigilance in

capturing and addressing ADR occurrences.6

2. Sai Nathan Ramnath et.al:

This was a retrospective analysis of ADRs reported to an AMC in South Kerala for a period of

3 years from October 2017 to September 2020 after obtaining Institutional Ethics Committee

clearance. The data were entered in Excel and analyzed using SPSS 16. During the period under study,

634 ADRs were reported with a mean age of 48.75 ± 19.25 years. The most common organ affected

was skin and appendages followed by the hepatobiliary system. The most common ADRs reported

were itching, maculopapular rash, and elevated liver enzymes. Antimicrobials accounted for the

maximum ADRs of which beta-lactams were the most common. The median time for occurrence of

ADRs was after 4 days (interquartile range: 1.30). The majority of ADRs were probable, preventable,

had moderate severity, and non-serious. Skin and integumentary followed by hepatobiliary system

were the most common ADRs and isoniazid was the most common drug associated with ADRs.

Conclusion: Antimicrobials accounted for the maximum number of ADRs which were dominated by

beta-lactams and antituberculosis drugs. Prospective studies on the development of ADRs will give

better understanding of the temporality as well as outcome and management of ADRs.7

3. Manodeep Sen et al:

Adverse drug reactions (ADRs) are a major cause of morbidity and mortality in hospitals

and pose great economic burden on the health care system. This study was conducted with the aim of

creating awareness and developing a culture for proper communication and reporting of ADRs

among health care professionals.This study is a retrospective analysis of total 60 reported ADRs from

AMC at a tertiary care hospital during a period of 14 months from March 2015 to April 2016. These
 ADRs were analysed for the pattern and type of reactions, body systems involved, causative drugs,

and severity of reaction, their outcome, management and causality assessment. Patients in the age

groups of 41-50 years were most commonly involved with slight male preponderance. Skin reactions

like rashes and itching were the most commonly observed ADR. The most common causative drugs

for ADR were antimicrobial agents; IV route was the most common route responsible. Majority of

ADRs belonged to type B, were non serious and moderate in severity. Most of the patients recovered.

On causality assessment scale, most of the ADRs were found to be probable with the causative drugs.

Most of the ADRs were treatable by early and appropriate management. The major limitation was

under-reporting of ADRs which can be overcome by creating awareness and enhancing the culture of

ADR monitoring and reporting among health care professionals for safe use of drugs.8

Method of Study:

After getting due permission from the scientific and ethics committee in our institute, the study

will be started. This retrospective study evaluates ADRs reported in tertiary care hospital. The ADRs

reported in suspected ADR reporting forms as a part of the PvPI from the various inpatient

departments from February 2024 to July 2024 will be analyzed after obtaining Institutional Ethics

Committee clearance. The institution was approved as an AMC under the PvPI with access to

VigiFlow. The data will be entered in a structured proforma. The age, gender, suspected drug causing

ADR, group of drugs, the ADR, and the organ system affected will be entered. Causality will be

assessed by the World Health Organization-Uppsala Monitoring Centre scale. Severity and

Preventability of the ADRs will be assessed by the modified Causality assessment. The data about the

history of drug intake, names of the drug taken, time lag of appearance of reaction, and clinical
examination details will be collected from the reports. Patient case notes/files and suspected ADR

forms will be used as main sources of data collection.

Study Design-

This is Retrospective Study

Sample size:

Sample size estimation was done using OpenEpi software version 2.3.1.

At 95% confidence level,

According to the study conducted by Manodeep S ()

Most common adverse event following treatment was cutaneous =45%=p

At 5%, Absolute precision,

Sample size estimated is 381, which is rounded off to 400.

Formula used n= [DEFF*Np(1-p)]/ [(d2/Z21-α/2*(N-1)+p*(1-p)]

Study Design: It is a Hospital based cross-sectional study

Plan for statistical analysis of the study:

Statistical analysis will be done using SPSS software 19.0.

Data obtained will be tabulated in the Excel sheet and will be analysed.

Quantitative data will be expressed as mean + standard deviation and nonparametric data will be expressed as
median and min-max values. Percentages are used for representing qualitative data.

Chi-square test for proportions in qualitative data.

Student’s unpaired t – test for Quantitative data.

Other appropriate statistical tests will be applied.

P< 0.05 will be considered statistically significant.

Study Location –
 This study will be conducted at S N Medical College and HSK Hospital and Research

Centre,Bagslkot.

Study Setting –

This study is based on Those Patients Who Experienced Adverse Drug Reaction to Medicine Used.

Study Criteria –

Inclusion Criteria;

ADRs reported to B.V.V.S Hanaga Shri Kumareshwar College of Pharmacy AMC Center

under PvPI from the duration January 2024 to June 2024

Exclusion Criteria;

ADRs which are not reported to B.V.V.S Hanaga Shri Kumareshwar College of Pharmacy AMC Center.

Age Criteria –

This Study is Conducted on Patients of All Age Groups

 Pediatrics (0 to 12 years)

 Adolescents (13 to 18 years)

 Young adults (19 to 30 years)

 Adults (30 to 40 years)

 Middle adults (40 to 60 years)

 Old adults (60 years and above)

Sources Of Data-
 1. ADR notification form of Suspected ADR.
2. CDSCO form.
3. Vigiflow form.

Analysis Of Result:

Seriousness of the reaction

Outcome
Action taken
Gender
Casuality assessment
Route of administritation
Drug type

Annexures:

Reference:
1. A.Tamil Bharathi, N.sivasankari, M S. Rajeswari.h, Dr. B. Sreelekha. Retrospective study

on adverse drug reaction in a tertiary care hospital. IJPBS. Oct 2016; 7(4): 294 – 298

2. Aaseer Thamby Sam, Looi Li ian Jessica, Subramani Parasuraman. A retrospective study

on the incidences of adverse drug events and analysis of the contributing trigger factors.

JBCP .March-May 2015; 6 (2):64-68.

3. Huaqiao Jiang, Yanhua Lin, Weifang Ren, Zhonghong Fang, Yujuan Liu, Xiaofang Tan,et

al, Adverse drug reactions and correlations with drug–drug interactions: A retrospective

study of reports from 2011 to 2020, Front. Pharmacol. August 2022; 13(13-2022):1-14

4. Vaishali Thakare, Anant Patil, Mukta Jain, Vivek Rai, Deepak Langade. Adverse drug

reactions reporting: five years analysis from a teaching hospital. JFMPC. November

2022;11(11): 7317-7321.

5. Pauline Packiaseeli, a retrospective analysis of reported cutaneous adverse drug reactions in

a tertiary care teaching hospital.ajpcr. August 2023; 17(1, 2024):27-29

6. Mukadam MF, Gawali PU. Adverse Drug Reactions: A Retrospective Analysis from the

ADR Monitoring Centre at a Tertiary Care Hospital.J Pharm Care 2024;12(1): 3-8

7. Ramnath SN, Nair PV, Philip MM, Palappallil DS. Adverse drug reactions reported to an

ADR monitoring centre as a part of the Pharmacovigilance Programme of India: A

retrospective analysis of 3-year data. NJPPP.July2023;13(09):1893-1897.

8. Sen M, Singh A, Misra M. Retrospective analysis of adverse drug reactions reported at ADR

monitoring centre under pvpi in a tertiary care hospital. Int J Basic Clin Pharmacol.

February 2018;7:303-308.