Association of empagliflozin treatment with changes in the metabolic score for insulin resistance in Iraqi adults with type 2 diabetes: a 6-month prospective cohort study
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20262782Abstract
Background: The metabolic score for insulin resistance (METS-IR) is an insulin-free surrogate that combines fasting plasma glucose, triglycerides, body mass index, and high-density lipoprotein cholesterol. Evidence on its responsiveness to sodium-glucose cotransporter 2 (SGLT2) inhibition is limited.
Methods: In this 6-month prospective observational cohort study, 124 adults with type 2 diabetes were enrolled at Al-Yarmouk Teaching Hospital, Baghdad. Empagliflozin 10 mg/day was added to usual oral therapy in 62 patients according to routine prescribing and patient preference; 62 continued therapies without an SGLT2 inhibitor or glucagon-like peptide-1 receptor agonist. Complete-case analyses included 58 and 56 participants, respectively. The primary outcome was the between-group difference in change in METS-IR.
Results: At 6 months, mean METS-IR decreased from 48.6±6.2 to 42.8±5.8 in the empagliflozin group and from 49.1±6.5 to 48.5±6.4 in controls. The reported adjusted between-group difference was −5.42 points (95% CI −6.81 to −4.03; p<0.001). Empagliflozin exposure was also associated with larger reductions in HbA1c, body weight, body mass index, and triglycerides and a larger increase in HDL cholesterol. Within the empagliflozin group, change in METS-IR correlated with changes in HbA1c (r=0.48), triglycerides (r=0.41), and body mass index (r=0.35), but not fasting plasma glucose (r=0.18).
Conclusions: Empagliflozin initiation was associated with a clinically and statistically larger reduction in METS-IR over 6 months than continued non-SGLT2 therapy. Because METS-IR contains several treatment-responsive components and treatment allocation was nonrandom, the findings should be interpreted as evidence of metabolic improvement rather than direct proof of enhanced insulin sensitivity.
Metrics
References
DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237(3):E214-23. DOI: https://doi.org/10.1152/ajpendo.1979.237.3.E214
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9. DOI: https://doi.org/10.1007/BF00280883
Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000;23(1):57-63. DOI: https://doi.org/10.2337/diacare.23.1.57
Bello-Chavolla OY, Almeda-Valdes P, Gomez-Velasco D, Viveros-Ruiz T, Cruz-Bautista I, Romo-Romo A, et al. METS-IR, a novel score to evaluate insulin sensitivity, is predictive of visceral adiposity and incident type 2 diabetes. Eur J Endocrinol. 2018;178(5):533-44. DOI: https://doi.org/10.1530/EJE-17-0883
Qian T, Sheng X, Shen P, Fang Y, Deng Y, Zou G. Mets-IR as a predictor of cardiovascular events in the middle-aged and elderly population and mediator role of blood lipids. Front Endocrinol. 2023;14:1224967. DOI: https://doi.org/10.3389/fendo.2023.1224967
Yoon J, Heo SJ, Lee JH, Kwon YJ, Lee JE. Comparison of METS-IR and HOMA-IR for predicting new-onset CKD in middle-aged and older adults. Diabetol Metabolic Syndrome. 2023;15(1):230. DOI: https://doi.org/10.1186/s13098-023-01214-7
Duan M, Zhao X, Li S, Miao G, Bai L, Zhang Q, et al. Metabolic score for insulin resistance (METS-IR) predicts all-cause and cardiovascular mortality in the general population: evidence from NHANES 2001-2018. Cardiovasc Diabetol. 2024;23(1):243. DOI: https://doi.org/10.1186/s12933-024-02334-8
Al Jobori H, Daniele G, Adams J, Cersosimo E, Solis-Herrera C, Triplitt C, et al. Empagliflozin Treatment Is Associated With Improved β-Cell Function in Type 2 Diabetes Mellitus. J Clin Endocrinol Metabolism. 2018;103(4):1402-7. DOI: https://doi.org/10.1210/jc.2017-01838
Abdul-Ghani M, Al Jobori H, Daniele G, Adams J, Cersosimo E, Triplitt C, et al. Inhibition of Renal Sodium-Glucose Cotransport With Empagliflozin Lowers Fasting Plasma Glucose and Improves β-Cell Function in Subjects With Impaired Fasting Glucose. Diabetes. 2017;66(9):2495-502. DOI: https://doi.org/10.2337/db17-0055
Briand F, Mayoux E, Brousseau E, Burr N, Urbain I, Costard C, et al. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism. Diabetes. 2016;65(7):2032-8. DOI: https://doi.org/10.2337/db16-0049
Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373(22):2117-28. DOI: https://doi.org/10.1056/NEJMoa1504720
Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375(4):323-34. DOI: https://doi.org/10.1056/NEJMoa1515920
Kadowaki T, Nangaku M, Hantel S, Okamura T, von Eynatten M, Wanner C, et al. Empagliflozin and kidney outcomes in Asian patients with type 2 diabetes and established cardiovascular disease: Results from the EMPA-REG OUTCOME® trial. J Diabetes Investig. 2019;10(3):760-70. DOI: https://doi.org/10.1111/jdi.12971
Wanner C, Heerspink HJL, Zinman B, Inzucchi SE, Koitka-Weber A, Mattheus M, et al. Empagliflozin and Kidney Function Decline in Patients with Type 2 Diabetes: A Slope Analysis from the EMPA-REG OUTCOME Trial. J Am Soc Nephrol. 2018;29(11):2755-69. DOI: https://doi.org/10.1681/ASN.2018010103
Mayer GJ, Wanner C, Weir MR, Inzucchi SE, Koitka-Weber A, Hantel S, et al. Analysis from the EMPA-REG OUTCOME® trial indicates empagliflozin may assist in preventing the progression of chronic kidney disease in patients with type 2 diabetes irrespective of medications that alter intrarenal hemodynamics. Kidney Int. 2019;96(2):489-504. DOI: https://doi.org/10.1016/j.kint.2019.02.033
Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med. 2020;383(15):1413-24. DOI: https://doi.org/10.1056/NEJMoa2022190
Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021;385(16):1451-61. DOI: https://doi.org/10.1056/NEJMoa2107038
The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388(2):117-27. DOI: https://doi.org/10.1056/NEJMoa2204233
DeFronzo RA, Lewin A, Patel S, Liu D, Kaste R, Woerle HJ, et al. Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care. 2015;38(3):384-93. DOI: https://doi.org/10.2337/dc14-2364
Rodbard HW, Rosenstock J, Canani LH, Deerochanawong C, Gumprecht J, Lindberg SØ, et al. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. Diabetes Care. 2019;42(12):2272-81. DOI: https://doi.org/10.2337/dc19-0883
Sawada T, Uzu K, Hashimoto N, Onishi T, Takaya T, Shimane A, et al. Empagliflozin's Ameliorating Effect on Plasma Triglycerides: Association with Endothelial Function Recovery in Diabetic Patients with Coronary Artery Disease. J Atherosclerosis Thrombosis. 2020;27(7):644-56. DOI: https://doi.org/10.5551/jat.50807
Jojima T, Sakurai S, Wakamatsu S, Iijima T, Saito M, Tomaru T, et al. Empagliflozin increases plasma levels of campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes: Association with a slight increase in high-density lipoprotein cholesterol. Int J Cardiol. 2021;331:243-8. DOI: https://doi.org/10.1016/j.ijcard.2021.01.063
Imre E, Gunhan HG, Erel P, Ustay O. SGLT2 inhibitors improve plasma atherogenic biomarkers in patients with type 2 diabetes: a real-world retrospective observational study. Minerva Endocrinol. 2023;48(3):295-304. DOI: https://doi.org/10.23736/S2724-6507.21.03465-5
Szekeres Z, Sandor B, Bognar Z, Ramadan FHJ, Palfi A, Bodis B, et al. Clinical Study of Metabolic Parameters, Leptin and the SGLT2 Inhibitor Empagliflozin among Patients with Obesity and Type 2 Diabetes. Int J Mol Sci. 2023;24(5). DOI: https://doi.org/10.3390/ijms24054405
Neeland IJ, Eliasson B, Kasai T, Marx N, Zinman B, Inzucchi SE, et al. The Impact of Empagliflozin on Obstructive Sleep Apnea and Cardiovascular and Renal Outcomes: An Exploratory Analysis of the EMPA-REG OUTCOME Trial. Diabetes Care. 2020;43(12):3007-15. DOI: https://doi.org/10.2337/dc20-1096
Pan R, Zhang Y, Wang R, Xu Y, Ji H, Zhao Y. Effect of SGLT-2 inhibitors on body composition in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. PloS One. 2022;17(12):e0279889. DOI: https://doi.org/10.1371/journal.pone.0279889
Sánchez-García A, Simental-Mendía M, Millán-Alanís JM, Simental-Mendía LE. Effect of sodium-glucose co-transporter 2 inhibitors on lipid profile: A systematic review and meta-analysis of 48 randomized controlled trials. Pharmacol Res. 2020;160:105068. DOI: https://doi.org/10.1016/j.phrs.2020.105068
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ (Clinical research ed.). 2007;335(7624):806-8. DOI: https://doi.org/10.1136/bmj.39335.541782.AD
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502. DOI: https://doi.org/10.1093/clinchem/18.6.499
Perrone-Filardi P, Avogaro A, Bonora E, Colivicchi F, Fioretto P, Maggioni AP, et al. Mechanisms linking empagliflozin to cardiovascular and renal protection. Int J Cardiol. 2017;241:450-6. DOI: https://doi.org/10.1016/j.ijcard.2017.03.089
Downloads
Published
How to Cite
Issue
Section
