Comparison of Empagliflozin-Linagliptin with Empagliflozin- Metformin Combination Therapy in Assessing Cardiovascular Profile and Anemia in Type 2 Diabetic Patients
DOI:
https://doi.org/10.51985/Keywords:
Blood Pressure, Cardiovascular Diseases, C-Reactive Protein, Diabetes Mellitus, Empagliflozin, Linagliptin, MetforminAbstract
objective: This study aimed to compare the effects of empagliflozin-metformin versus empagliflozin- linagliptin combination therapy on cardiovascular parameters and anemia in patients with type 2 diabetes mellitus (T2DM).
Study Design and setting: An analytical study was conducted over 12 weeks at National Medical Centre Hospital, Karachi. Methodology: T2DM patients were randomly assigned to either the Empagliflozin 12. 5 mg with Metformin 500mg or Empagliflozin 10mg with Linagliptin 5mg. Clinical assessments were conducted at baseline Week 0, 4, and 12, focusing on C-reactive protein levels, blood pressure, temperature, heart rate, respiratory rate, ECG findings, hemoglobin levels, BMI, and glycated hemoglobin (HbA1c) and cardiac examination was performed in all visits. Descriptive statistics were used to compare outcomes between the groups.
Results: The comparative analysis of empagliflozin–metformin (EM) and empagliflozin–linagliptin (EL) regimens demonstrated notable differences in outcomes. HbA1c decreased significantly in both groups, but the EL group showed a greater reduction by week 12 (p = 0.021, OR = 1.65, 95% CI: 1.05–2.58). BMI declined in both arms, but intergroup difference was not statistically significant (p = 0.078). CRP levels dropped more in the EL group, reaching statistical significance (p = 0.037, OR = 1.43, 95% CI: 1.01–2.11). Cardiovascular parameters, including systolic BP (p = 0.116) and diastolic BP (p = 0.098), remained stable, showing no significant differences. ECG (QTc interval) changes were also nonsignificant (p = 0.316). Hemoglobin levels showed no significant difference between groups at week 12 (p = 0.212). Overall, both regimens were effective and cardiovascularly safe, though EL provided superior benefits in glycemic control (HbA1c, p = 0.021) and anti-inflammatory effect (CRP, p = 0.037).
Conclusion: The combination of empagliflozin with either metformin or linagliptin proved to be effective treatment with cardiovascular safety.
References
1. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal
A, Siddiqi H, Uribe KB, Ostolaza H, Martín C.
Pathophysiology of type 2 diabetes mellitus. International
journal of molecular sciences. 2020 Aug 30;21(17):6275.
2. Ye J, Li L, Wang M, Ma Q, Tian Y, Zhang Q, Liu J, Li B,
Zhang B, Liu H, Sun G. Diabetes mellitus promotes the
development of atherosclerosis: the role of NLRP3. Frontiers
in immunology. 2022 Jun 29;13:900254. Diabetes mellitus
promotes the development of atherosclerosis: the role of
NLRP3. Frontiers in immunology
3. Petrie JR, Guzik TJ, Touyz RM. Diabetes, hypertension, and
cardiovascular disease: clinical insights and vascular
mechanisms. Canadian Journal of Cardiology. 2018 May
1;34(5):575-84. DOI: 10.1016/j.cjca.2017.12.005
4. Radzioch E, D¹bek B, Balcerczyk-Lis M, Fr¹k W, Fularski
P, M³ynarska E, Rysz J, Franczyk B. Diabetic
cardiomyopathy—from basics through diagnosis to treatment.
Biomedicines. 2024 Mar 29;12(4):765.
5. Ma CX, Ma XN, Guan CH, Li YD, Mauricio D, Fu SB.
Cardiovascular disease in type 2 diabetes mellitus: progress
toward personalized management. Cardiovascular diabetology.
2022 May 14;21(1):74.
6. Feingold KR. Oral and injectable (non-insulin)
pharmacological agents for the treatment of type 2 diabetes.
Endotext [Internet]. 2024 Sep 11.
7. Tinahones FJ, Gallwitz B, Nordaby M, Götz S, MaldonadoLutomirsky M, Woerle HJ, Broedl UC. Linagliptin as addon to empagliflozin and metformin in patients with type 2
diabetes: two 24-week randomized, double-blind, doubledummy, parallel-group trials. Diabetes, Obesity and
Metabolism. 2017 Feb;19(2):266-74. doi: 10.1111/dom.
12814.Epub 2016 Nov 24
8. Bae JH, Park EG, Kim S, Kim SG, Hahn S, Kim NH.
Comparative renal effects of dipeptidyl peptidase-4 inhibitors
and sodium-glucose cotransporter 2 inhibitors on individual
outcomes in patients with type 2 diabetes: a systematic review
and network meta-analysis. Endocrinology and Metabolism.
2021 Mar 31;36(2):388-400. doi: 10.3803/EnM.2020.912.
Epub 2021 Mar 31.
9. Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A,
del Cañizo-Gómez FJ. Type 2 diabetes and cardiovascular
disease: have all risk factors the same strength?. World journal
of diabetes. 2014 Aug 15;5(4):444. doi: 10.4239/wjd.v5.i4.444
10. Li Y, Liu Y, Liu S, Gao M, Wang W, Chen K, Huang L, Liu
Y. Diabetic vascular diseases: molecular mechanisms and
therapeutic strategies. Signal transduction and targeted therapy.
2023 Apr 10;8(1):152. DOI: 10.1038/s41392-023-01400-z
11. Amezcua-Castillo E, González-Pacheco H, Sáenz-San Martín
A, Méndez-Ocampo P, Gutierrez-Moctezuma I, Massó F,
Sierra-Lara D, Springall R, Rodríguez E, Arias-Mendoza A,
Amezcua-Guerra LM. C-reactive protein: the quintessential
marker of systemic inflammation in coronary artery disease—
advancing toward precision medicine. Biomedicines. 2023
Sep 2;11(9):2444. doi: 10.3390/biomedicines11092444
12. Anker SD, Butler J, Filippatos G, Khan MS, Marx N, Lam
CS, Schnaidt S, Ofstad AP, Brueckmann M, Jamal W, Bocchi
EA. Effect of empagliflozin on cardiovascular and renal
outcomes in patients with heart failure by baseline diabetes
status: results from the EMPEROR-reduced trial. Circulation.
2021 Jan 26;143(4):337-49.
13. Kabil MF, Lababidi JM, Azzazy HM. Linagliptin: A
comprehensive profile. Profiles of Drug Substances, Excipients,
and Related Methodology. 2025 Jan 23;50:97. DOI:10.1016/bs.
podrm.2024.10.001.
14. Hostalek U, Campbell I. Metformin for diabetes prevention:
update of the evidence base. Current medical research and
opinion. 2021 Oct 3;37(10):1705-17. doi: 10.1080/03007995.
2021.1955667
15. Rena G, Hardie DG, Pearson ER. The mechanisms of action
of metformin. Diabetologia. 2017 Sep;60(9):1577-85. doi:
10.1007/s00125-017-4342-z
16. EMPA-Kidney Collaborative Group. Empagliflozin in patients
with chronic kidney disease. New England Journal of Medicine.
2023 Jan 12;388(2):117-27. doi: 10.1056/NEJMoa2204233
17. Xie D, Wang Q, Huang W, Zhao L. Dipeptidyl-peptidase-4
inhibitors have anti-inflammatory effects in patients with type
2 diabetes. European Journal of Clinical Pharmacology. 2023
Oct;79(10):1291-301. doi: 10.1007/s00228-023-03541-0
18. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E,
Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ,
Broedl UC. Empagliflozin, cardiovascular outcomes, and
mortality in type 2 diabetes. New england journal of medicine.
2015 Nov 26;373(22):2117-28. DOI: 10.1056/ NEJMoa1504
720
19. Rosenstock J, Kahn SE, Johansen OE, Zinman B, Espeland
MA, Woerle HJ, Pfarr E, Keller A, Mattheus M, Baanstra D,
Meinicke T. Effect of linagliptin vs glimepiride on major
adverse cardiovascular outcomes in patients with type 2
diabetes: the CAROLINA randomized clinical trial. Jama.
2019 Sep 24;322(12):1155-66. doi: 10.1001/jama.2019.13772
20. Li YR, Tsai SS, Chen DY, Chen ST, Sun JH, Chang HY, Liou
MJ, Chen TH. Linagliptin and cardiovascular outcomes in
type 2 diabetes after acute coronary syndrome or acute ischemic
stroke. Cardiovascular Diabetology. 2018 Jan 4;17(1):2. doi:
10.1186/s12933-017-0655-y
21. Infante M, Leoni M, Caprio M, Fabbri A. Long-term metformin
therapy and vitamin B12 deficiency: an association to bear
in mind. World journal of diabetes. 2021 Jul 15;12(7):916.
doi: 10.4239/wjd.v12.i7.916.
Downloads
Published
Issue
Section
License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Journal of Bahria University Medical & Dental College is an open access journal and is licensed under CC BY-NC 4.0. which permits unrestricted non commercial use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc/4.0