Comparative Effectiveness of Glimepiride versus Linagliptin as add-on to Metformin in Type-2-Diabetes Mellitus
Abstract
Background: In addition to lifestyle modifications, metformin is the recommended first-line pharmacotherapy for patients with type 2 diabetes mellitus (T2DM). The use of glimepiride or linagliptin as add-on to metformin (GM or LM) has been noticed on prescriptions in major pharmacies in Nigeria.
Aims: The aim of this study was to compare the efficacy of glimepiride or linagliptin as add-on to metformin in T2DM.
Methods: A preliminary case-crossover randomized experimental/observational study comprising 30 participants (i.e., 15 for each of the combination therapies) was designed and designated GM and LM groups, respectively. Baseline physiological and health-indicators of the participants were primarily observed followed by a practical/analytical drug efficacy measurement of postprandial blood glucose (PPBG) levels at 1, 2, 4, and 6 h once weekly for 2 weeks and thereafter crossover to the other regimen for another two weeks’ assessment.
Results: Baseline results were consistent across subgroup analyses in both treatment types. The statistical analysis demonstrated that LM achieved significant PPBG lowering potential compared to baseline blood glucose status (p<0.05). There was no significant difference in the observed physiological and biochemical indicators of organ system function for both treatments during the study. Treatment with LM was associated with reduced post-meal blood glucose compared with GM (p<0.05). Postprandial blood glucose change over measurement points were higher with LM (p<0.05).
Conclusion: Blood glucose control was better achieved with LM compared to GM. Propensity to hypoglycemia was higher with LM. More studies involving larger patient population in several centres are required to validate the outcome of these findings.
Keywords: Glimepiride, Linagliptin, Metformin, Fasting Blood Glucose, Postprandial blood glucose, Type 2 Diabetes Mellitus
Keywords:
Glimepiride, Linagliptin, Metformin, Fasting Blood Glucose, Postprandial blood glucose, Type 2 Diabetes MellitusDOI
https://doi.org/10.22270/jddt.v13i6.5879References
American Diabetes Association, Standards of Medical Care in Diabetes, Diabetes Care. 2013; 36(suppl.1): S11-66. https://doi.org/10.2337/dc13-S011
Madiraju AK, Qiu Y, Perry RJ, Rahimi Y, Zhang XM, Zhang D, Camporez JG, Cline GW, Butrico GM, Kemp BE, Casals G, Steinberg GR, Vatner DF, Petersen KF, Shulman GI, Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo, Nature Medicine, 2018; 24(9):1384-1394. Epub 2018 Jul 23. Erratum in: Nat Med. 2019 Mar; 25(3):526-528. PMID: 30038219. https://doi.org/10.1038/s41591-018-0125-4
World Health Organization, About Diabetes. Archived from the original on 31 March 2014. Retrieved 4 April, 2022.
Zhang L, Li L, Yang M, Liu H, Yang G, Elevated circulating vaspin levels were decreased by rosiglitazone therapy in T2DM patients with poor glyceamic control on metformin alone, Cytokine, 2011; 56(2):399-402Epub 2011 Jul 29. PMID: 21802961 https://doi.org/10.1016/j.cyto.2011.07.003
Mullugeta Y, Chawla R, Kebede T, Worku Y, Dyslipidemia associated with poor glyceamic control in type 2 diabetes mellitus and the protective effect of metformin supplementation, Indian Journal of Clinical Biochemistry, 2012 Oct; 27(4):363-9. Epub 2012 Jun 6. PMID: 24082461. https://doi.org/10.1007/s12291-012-0225-8
Sola D, Rossi L, Schianca GP, Maffioli P, Bigliocca M, Mella R, Corlianò F, Fra GP, Bartoli E, Derosa G, Sulfonylureas and their use in clinical practice, Archives of Medical Science, 2015; 11(4):840-8Epub, 2015 Aug 11. PMID: 26322096; PMCID: PMC4548036. https://doi.org/10.5114/aoms.2015.53304
Forst T, Pfützner A, Linagliptin, a dipeptidyl peptidase-4 inhibitor with a unique pharmacological profile, and efficacy in a broad range of patients with type 2 diabetes, Expert Opinion on Pharmacotherapy, 2012; 13(1):101-10. PMID: 22149370. https://doi.org/10.1517/14656566.2012.642863
McGill JB, Linagliptin for Type 2 Diabetes Mellitus: a review of the pivotal clinical trials, Therapeutic Advances in Endocrinology and Metabolism, 2012; 3(4): 113-124. PMID: 23185685 https://doi.org/10.1177/2042018812449406
World Medical Association, World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects, Journal of American Medical Association, 2013; 310(20): 2191-4 PMID: 24141714. https://doi.org/10.1001/jama.2013.281053
Charpentier G, Fleury F, Kabir M, Vaur L, Halimi S, Improved glycaemic control by addition of glimepiride to metformin monotherapy in type 2 diabetic patients, Diabetic Medicine, 2001; 18(10):828-34. PMID: 11678974. https://doi.org/10.1046/j.1464-5491.2001.00582.x
Fuschs H, Tillement JP, Urien S, Greischel A, Roth W, Concentration dependent plasma protein binding of the novel dipeptidyl peptidase-4 inhibitor BI 1356 due to saturable binding to its target in the plasma of mice, rats and humans. Journal of Pharmacy and Pharmacology, 2009; 61:55-62. https://doi.org/10.1211/jpp.61.01.0008
Glasgow R, Anderson R, In diabetes care, moving from compliance to adherence is not enough. Something entirely different is needed, Diabetes Care. 1999; 22:2090-2 https://doi.org/10.2337/diacare.22.12.2090
Gallwitz B, Rosenstock J, Rauch T, Bhattacharya S, Patel S, von Eynatten M, Dugi KA, Woerle HJ, 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial, Lancet, 2012; 380(9840):475-83. Epub 2012 Jun 28. PMID: 22748821. https://doi.org/10.1016/S0140-6736(12)60691-6
Devarajan TV, Venkataram S, Kandadamy N, Ooman A, Boorugu HH, Karuppiah SK, Balat D, Comparative Evaluation and Efficacy of Glimepiride and Sitagliptin in Combination with Metformin in Patient with Type 2 Diabetes Mellitus: Indian Multicentric Randomized Trial -START Studies, Indian Journal of Endocrinology and Metabolism, 2017; 21(5):745-750 https://doi.org/10.4103/ijem.IJEM_176_17
McCulloch DK, Munshi M, Treatment of type 2 diabetes mellitus in the older patient. UpToDate. 2016. Uptodate.com/contents/treatment-of-type-2-diabetes-mellitus-in-the-older-patient. Updated May 9, 2016. Accessed June 30, 2016
Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B, IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Research and Clinical Practice, 2018; 138:271-281. Epub 2018 Feb 26. PMID: 29496507. https://doi.org/10.1016/j.diabres.2018.02.023
Nauck M, Araki A, Hehnke U, Plat A, Clark D, Khunti K, Risk of hypoglycaemia in people aged ≥65 years receiving linagliptin: pooled data from 1489 individuals with type 2 diabetes mellitus, International Journal of Clinical Practice. 2018; 72(10):e13240. PMID: 30216648. https://doi.org/10.1111/ijcp.13240
Graefe-Mody U, Friedrich C, Port A, Ring A, Retlich S, Heise T, Halabi A, Woerle HJ, Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin, Diabetes Obesity and Metabolism, 2011; 13(10):939-46. PMID: 21672124. https://doi.org/10.1111/j.1463-1326.2011.01458.x
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