Efficacy and safety of Dapagliflozin and Glimepiride in combination with Metformin: Randomized clinical trial

Authors

  • Muhammad Kamran Yousuf
  • Khalid Mustafa Memon
  • Muhammad Sajid Abbas Jaffri
  • Mehr Fatima
  • Mamoora Arslaan
  • Shizma Junejo

DOI:

https://doi.org/10.51985/JBUMDC2024437

Keywords:

Type 2 diabetes mellitus, glimepiride, dapagliflozin, fasting blood glucose, glycated hemoglobin`

Abstract

Objective: To identify the effective treatment option between dapagliflozin-metformin and glimepiride-metformin combination in patients with type 2 diabetes who were inadequately controlled with metformin monotherapy.

 

Study design and setting: The present study is randomized, conducted for 12 weeks at the National Medical center, Karachi, Pakistan.

 

Methodology: The patients were divided into 2 treatment groups; group A was given dapagliflozin-metformin combination, while group B was given glimepiride-metformin combination. The efficacy endpoint of groups was estimated by hemoglobin A1c and fasting blood glucose levels at 0-, 6- and 12-week. While, safety endpoints were identified by analyzing liver function tests, lipid profile tests, renal function test, and urine analysis. The significant difference of data was analyzed by using statistical package of social sciences (SPSS) version 25. The parametric t-test and paired t-test were performed and considered p-value = 0.05 as statistical significant.

 

Results: Baseline demographics, clinical features of diabetes, levels of liver enzymes, liver function test, renal function test, lipid profile, and urinalysis of randomized patients were similar in both treatment groups by showing p = 0.05. Followed by the initiation of the respective treatment, the baseline change of mean FBG and hemoglobin A1c levels with dapagliflozinmetformin combination was shown significantly reduce more compared to glimepiride-metformin combination (p = 0.05). Conclusion: Dapagliflozin-metformin combination therapy was superior and well-tolerated to regulate glycemic control as compare to glimepiride-metformin combination

References

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S,

Unwin N, et al. Global and regional diabetes prevalence

estimates for 2019 and projections for 2030 and 2045: Results

from the International Diabetes Federation Diabetes Atlas,

th edition. Diabetes Research and Clinical Practice.

;157:107843. DOI: 10.1016/j.diabres.2019.107843

Kim J, Park S, Kim H, Je NK. National trends in metforminbased combination therapy of oral hypoglycaemic agents for

type 2 diabetes mellitus. European journal of clinical pharmacology. 2019 ;75:1723-30. DOI: 10.1007/s00228-019-02751-

Dahlén AD, Dashi G, Maslov I, Attwood MM, Jonsson J,

Trukhan V, Schiöth HB. Trends in antidiabetic drug discovery:

FDA approved drugs, new drugs in clinical trials and global

sales. Frontiers in Pharmacology. 2022 ;12:807548. DOI:

3389/fphar.2021.807548

Nauck MA, Del Prato S, Durán-García S, Rohwedder K,

Langkilde AM, Sugg J, et al. Durability of glycaemic efficacy

over 2 years with dapagliflozin versus glipizide as add-on

therapies in patients whose type 2 diabetes mellitus is inadequately controlled with metformin. Diabetes, obesity &

metabolism. 2020;16(11):1111-20. DOI: 10.1111/dom.12327

Nauck MA, Del Prato S, Meier JJ, Durán-García S, Rohwedder

K, Elze M, et al. Dapagliflozin versus glipizide as add-on

therapy in patients with type 2 diabetes who have inadequate

glycemic control with metformin: a randomized, 52-week,

double-blind, active-controlled noninferiority trial. Diabetes

Care. 2019;34(9):2015-22. DOI: 10.2337/dc11-0606

Del Prato S, Nauck M, Durán-Garcia S, Maffei L, Rohwedder

K, Theuerkauf A, et al. Long-term glycaemic response and

tolerability of dapagliflozin versus a sulphonylurea as addon therapy to metformin in patients with type 2 diabetes: 4-

year data. Diabetes, obesity & metabolism. 2015;176:581-

DOI: 10.1111/dom.12459

Sezai A, Tanaka A, Imai T, Kida K, Sekino H, Murohara T,

Sata M, Suzuki N, Node K; CANDLE Trial Investigators.

Comparing the Effects of Canagliflozin vs. Glimepiride by

Body Mass Index in Patients with Type 2 Diabetes and Chronic

Heart Failure: A Subanalysis of the CANDLE Trial. Biomedicines. 2022 Jul 9;10(7):1656. doi: 10.3390/ biomedi cines100

PMID: 35884961

Ridderstråle M, Andersen KR, Zeller C, Kim G, Woerle HJ,

Broedl UC. Comparison of empagliflozin and glimepiride as

add-on to metformin in patients with type 2 diabetes: a 104-

week randomised, active-controlled, double-blind, phase 3

trial. The lancet Diabetes & endocrinology. 2018;2(9):691-

doi.org/10.1111/dom.13457

Riddle MC. A Verdict for Glimepiride: Effective and Not

Guilty of Cardiovascular Harm. Diabetes Care. 2019;42(12):

-3.

Trerattanavong K, Tadi P. Glimepiride. StatPearls. Treasure

Island (FL): StatPearls Publishing Copyright © 2020, StatPearls

Publishing LLC.; 2020.

Melillo G. FDA approves dapagliflozin to treat heart failure,

breaking new ground in SGLT2 competition. American Journal

of Managed Care. 2020;1.

Raj GM, Wyawahare M. Dapagliflozin for heart failure: is

it a class effect?. Future cardiology. 2021 ;17(2):355-61. DOI:

2217/fca-2020-0087

Shao S-C, Chang K-C, Hung M-J, Yang N-I, Chan Y-Y, Chen

H-Y, et al. Comparative risk evaluation for cardiovascular

events associated with dapagliflozin vs. empagliflozin in realworld type 2 diabetes patients: a multi-institutional cohort

study. Cardiovascular Diabetology. 2019;18(1):120. doi.org/

1186/s12933-019-0919-9

Mosleh H, Alenezi M. Prevalence and factors of anxiety and

depression in chronic kidney disease patients undergoing

hemodialysis: A cross-sectional single-center study in Saudi

Arabia. Cureus. 2020;12(1). DOI: 10.7759/cureus.6668

Bailey CJ, Gross JL, Hennicken D, Iqbal N, Mansfield TA,

List JF. Dapagliflozin add-on to metformin in type 2 diabetes

inadequately controlled with metformin: a randomized, doubleblind, placebo-controlled 102-week trial. BMC medicine.

;11:43. doi: 10.1186/1741-7015-11-43

Rosenstock J, Perl S, Johnsson E, García-Sánchez R, Jacob

S. Triple therapy with low-dose dapagliflozin plus saxagliptin

versus dual therapy with each monocomponent, all added to

metformin, in uncontrolled type 2 diabetes. Diabetes Obes

Metab. 2019 Sep;21;9;2152-2162. doi: 10.1111/dom.13795.

Sjöström CD, Johansson P, Ptaszynska A, List J, Johnsson E.

Dapagliflozin lowers blood pressure in hypertensive and nonhypertensive patients with type 2 diabetes. Diabetes & vascular

disease research. 2015;12(5):352-8. DOI: 10.1177/ 147916411

Yamout H, Perkovic V, Davies M, Woo V, de Zeeuw D, Mayer

C, et al. Efficacy and safety of canagliflozin in patients with

type 2 diabetes and stage 3 nephropathy. American journal

of nephrology. 2014;40(1):64-74. DOI: 10.1159/000364909

Scholtes RA, Muskiet MH, van Baar MJ, Hesp AC, Greasley

PJ, Karlsson C, et al. Natriuretic effect of two weeks of

dapagliflozin treatment in patients with type 2 diabetes and

preserved kidney function during standardized sodium intake:

results of the DAPASALT trial. Diabetes Care. 2021

;44(2):440-7. doi: 10.2337/dc20-2604

Sjöström CD, Hashemi M, Sugg J, Ptaszynska A, Johnsson

E. Dapagliflozin-induced weight loss affects 24-week glycated

haemoglobin and blood pressure levels. Diabetes, obesity &

metabolism. 2015;17(8):809-12. DOI: 10.1177/ 1479164115

Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel

A. Blood Pressure Lowering in Type 2 Diabetes: A Systematic

Review and Meta-analysis. JAMA. 2015;313;6;603–615.

doi:10.1001/jama.2014.18574

Vilsbøll T, Ekholm E, Johnsson E, et al. Efficacy and safety

of dapagliflozin plus saxagliptin versus insulin glargine over

weeks as add-on to metformin with or without sulphonylurea

in patients with type 2 diabetes: A randomized, parallel-design,

open-label, Phase 3 trial. Diabetes Obes Metab. 2020; 22:

–968. https://doi.org/10.1111/dom.13981

Mathieu C, Ranetti AE, Li D, Ekholm E, Cook W, Hirshberg

B, et al. Randomized, Double-Blind, Phase 3 Trial of Triple

Therapy With Dapagliflozin Add-on to Saxagliptin Plus

Metformin in Type 2 Diabetes. Diabetes Care. 2015;38(11)

:2009-17. DOI: 10.2337/dc15-0779

Fadini GP, Bonora BM, Mayur S, Rigato M, Avogaro A.

Dipeptidyl peptidase-4 inhibitors moderate the risk of genitourinary tract infections associated with sodium-glucose cotransporter-2 inhibitors. 2018;20(3):740-4. DOI: 10.1111/dom.

Gopal CDSM, Rathi S, Tyagi S. Clinical profile of hypoglycemia in emergency department of tertiary care hospital: A

single center study. International Journal of Advanced Research

in Medicine 2021; 3(1): 340-343.DOI: 10.22271/27069567.

v3.i1f.162

Downloads

Published

2024-10-08

How to Cite

Yousuf, M. K. ., Memon, K. M. ., Jaffri, M. S. A. ., Fatima, M. ., Arslaan, M. ., & Junejo, S. . (2024). Efficacy and safety of Dapagliflozin and Glimepiride in combination with Metformin: Randomized clinical trial. Journal of Bahria University Medical and Dental College, 14(04), 268–273. https://doi.org/10.51985/JBUMDC2024437

Issue

Section

Original Articles