Effectiveness of using a fixed combination of alogliptin and pioglitazone, providing a protective cardiometabolic effect in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease
AbstractThe aim of the work is to demonstrate, using a clinical example, the possibility of using a fixed-dose combination of alogliptin/pioglitazone in the treatment of the patient with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).
Material and methods. A clinical case of the comorbid patient using modern methods of diagnosis, treatment and monitoring of T2DM and NAFLD is presented.
Results. The use of a drug with a fixed-dose combination of alogliptin/pioglitazone as initiation of therapy in the patient with newly diagnosed T2DM and NAFLD had a significant clinical effect on both comorbid diseases. There was a redistribution of body composition with a decrease in the level of visceral adipose tissue, improvement in carbohydrate and lipid metabolism, markers for non-invasive diagnosis of non-alcoholic steatohepatitis and liver fibrosis.
Conclusion. The solution to the issue of optimal treatment of comorbid diseases such as T2DM and NAFLD is based on providing simultaneous effects on both diseases, ensuring rationalization of economic costs and having a high profile of effectiveness and safety.
Keywords: carbohydrate metabolism disorder; type 2 diabetes mellitus; non-alcoholic fatty liver disease; pioglitazone; alogliptin; NASH-FibroTest
Funding. The study had no sponsor support.
Conflict of interest. The authors declare no conflict of interest.
For citation: Pyanykh O.P., Gurieva I.V. Effectiveness of using a fixed combination of alogliptin and pioglitazone, providing a protective cardiometabolic effect in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. Endokrinologiya: novosti, mneniya, obuchenie [Endocrinology: News, Opinions, Training]. 2024; 13 (2): 61–68. DOI: https://doi.org/10.33029/2304-9529-2024-13-2-61-68 (in Russian)
References
1. Jichitu A., Bungau S., Stanescu A.M.A., et al. Non-alcoholic fatty liver disease and cardiovascular comorbidities: pathophysiological links, diagnosis, and therapeutic management. Diagnostics (Basel). 2021; 11 (4): 689. DOI: https://doi.org/10.3390/diagnostics11040689
2. Harrison S.A., Gawrieh S., Roberts K., et al. Prospective evaluation of the prevalence of non-alcoholic fatty liver disease and steatohepatitis in a large middle-aged US cohort. J Hepatol. 2021; 75: 284–91.
3. Rinella M.E., Neuschwander-Tetri B.A., Siddiqui M.S., et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023; 77 (5): 1797–835. DOI: https://doi.org/10.1097/HEP.0000000000000323
4. Cusi K., Isaacs S., Barb D., Basu R., Caprio S., et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022; 28 (5): 528–62. DOI: https://doi.org/10.1016/j.eprac.2022.03.010 PMID: 35569886.
5. Маевская М.В., Котовская Ю.В., Ивашкин В.Т. и др. Консенсус для врачей по ведению взрослых пациентов с неалкогольной жировой болезнью печени и ее основными коморбидными состояниями // Терапевтический архив. 2022. Т. 94, № 2. С. 216–253. DOI: https://doi.org/10.26442/00403660.2022.02.201363 [Maevskaya M., Kotovskaya Y., Ivashkin V., et al. The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities. Terapevticheskiy arkhiv [Therapeutic Archive]. 2022; 94 (2): 216–53. DOI: https://doi.org/10.26442/00403660.2022.02.201363 (in Russian)]
6. Gastaldelli A., Sabatini S., Carli F., et al. PPAR-g-induced changes in visceral fat and adiponectin levels are associated with improvement of steatohepatitis in patients with NASH. Liver Int. 2021; 41 (11): 2659–70.
7. Lomonaco R., Godinez Leiva E., Bril F., et al. Advanced liver fibrosis is common in patients with type 2 diabetes followed in the outpatient setting: the need for systematic screening. Diabetes Care. 2021; 44: 399–406.
8. Lomonaco R., Bril F., Portillo-Sanchez P., et al. Metabolic impact of nonalcoholic steatohepatitis in obese patients with type 2 diabetes. Diabetes Care. 2016; 39 (4): 632–8.
9. Mantovani A., Zaza G., Byrne C.D., et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: a systematic review and meta-analysis. Metabolism. 2018; 79: 64–76.
10. Kanwal F., Shubrook J.H., Younossi Z., Natarajan Y., Bugianesi E., Rinella M.E., et al. Preparing for the NASH epidemic: a call to action. Diabetes Care. 2021; 44 (9): 2162–72. DOI: https://doi.org/10.2337/dci21-0020
11. Angulo P., Kleiner D.E., Dam-Larsen S., et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015; 149 (2): 389–97.e10. DOI: https://doi.org/10.1053/j.gastro.2015.04.043
12. Polyzos S.A., Kang E.S., Boutari C., et al. Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis. Metabolism. 2020; 111S: 154203. DOI: https://doi.org/10.1016/j.metabol.2020.154203
13. Belfort R., Harrison S.A., Brown K., et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006; 355: 2297–307.
14. Musso G., Cassader M., Paschetta E., Gambino R. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: a meta-analysis. JAMA Intern Med. 2017; 177 (5): 633–40. DOI: https://doi.org/10.1001/jamainternmed.2016.9607
15. Boettcher E., Csako G., Pucino F., et al. Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2012; 35 (1): 66–75. DOI: https://doi.org/10.1111/j.1365-2036.2011.04912.x
16. Loomba R., Lutchman G., Kleiner D.E., et al. Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2009; 29 (2): 172–82.
17. Bugianesi E., Gentilcore E., Manini R., et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol. 2005; 100 (5): 1082–90.
18. Musso G., Cassader M., Rosina F., Gambino R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia. 2012; 55 (4): 885–904.
19. Sawangjit R., Chongmelaxme B., Phisalprapa P., et al. Comparative efficacy of interventions on nonalcoholic fatty liver disease (NAFLD): a PRISMA-compliant systematic review and network meta-analysis. Medicine (Baltimore). 2016; 95 (32): e4529.
20. Li Y., Liu L., Wang B., Wang J., Chen D. Metformin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Biomed Rep. 2013; 1 (1): 57–64.
21. Sanyal A.J., Chalasani N., Kowdley K.V., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010; 362 (18): 1675–85.
22. Cusi K., Orsak B., Bril F., et al. Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus: a randomized trial. Ann Intern Med. 2016; 165 (5): 305–15.
23. Aithal G.P., Thomas J.A., Kaye P.V., et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology. 2008; 135 (4): 1176–84.
24. Bril F., Biernacki D.M., Kalavalapalli S., et al. Role of vitamin E for nonalcoholic steatohepatitis in patients with type 2 diabetes: a randomized controlled trial. Diabetes Care. 2019; 42 (8): 1481–8.
25. Newsome P.N., Buchholtz K., Cusi K., et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021; 384 (12): 1113–24.
26. Cusi K. Incretin-based therapies for the management of nonalcoholic fatty liver disease in patients with type 2 diabetes. Hepatology. 2019; 69 (6): 2318–22.
27. Patel Chavez C., Cusi K., Kadiyala S. The emerging role of glucagon-like peptide-1 receptor agonists for the management of NAFLD. J Clin Endocrinol Metab. 2022; 107 (1): 29–38.
28. Armstrong M.J., Gaunt P., Aithal G.P., et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (lean): a multicentre, double- blind, randomised, placebo-controlled phase 2 study. Lancet. 2016; 387 (10 019): 679–90.
29. Cusi K. Time to include nonalcoholic steatohepatitis in the management of patients with type 2 diabetes. Diabetes Care. 2020; 43 (2): 275–9.
30. Cusi K., Bril F., Barb D., et al. Effect of canagliflozin treatment on hepatic tri- glyceride content and glucose metabolism in patients with type 2 diabetes. Diabetes Obes Metab. 2019; 21 (4): 812–21.
31. Latva-Rasku A., Honka M.J., Kullberg J., et al. The SGLT2 inhibitor dapagliflozin reduces liver fat but does not affect tissue insulin sensitivity: a randomized, double-blind, placebo-controlled study with 8-week treatment in type 2 diabetes patients. Diabetes Care. 2019; 42 (5): 931–7.
32. Kahl S., Gancheva S., Straßburger K., et al. Empagliflozin effectively lowers liver fat content in well-controlled type 2 diabetes: a randomized, double-blind, phase 4, placebo-controlled trial. Diabetes Care. 2020; 43 (2): 298–305.
33. Smits M.M., Tonneijck L., Muskiet M.H., et al. Twelve week liraglutide or sitagliptin does not affect hepatic fat in type 2 diabetes: a randomised placebo-controlled trial. Diabetologia. 2016; 59 (12): 2588–93.
34. Joy T.R., McKenzie C.A., Tirona R.G., et al. Sitagliptin in patients with non-alcoholic steatohepatitis: a randomized, placebo-controlled trial. World J Gastroenterol. 2017; 23 (1): 141–50.
35. Cui J., Philo L., Nguyen P., et al. Sitagliptin vs. placebo for non-alcoholic fatty liver disease: a randomized controlled trial. J Hepatol. 2016; 65 (2): 369–76.
36. Lingvay I., Raskin P., Szczepaniak L.S. Effect of insulin-metformin combination on hepatic steatosis in patients with type 2 diabetes. J Diabetes Complications. 2007; 21 (3): 137–42.
37. Juurinen L., Tiikkainen M., Hakkinen A.M., Hakkarainen A., Yki-Jarvinen H. Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes. Am J Physiol Endocrinol Metab. 2007; 292 (3): E829–35.
38. Cusi K., Sanyal A.J., Zhang S., et al. Different effects of basal insulin peglispro and insulin glargine on liver enzymes and liver fat content in patients with type 1 and type 2 diabetes. Diabetes Obes Metab. 2016; 18 (suppl 2): 50–8.
39. Tomlinson B., Chan P., Lam C.W.K. An overview of alogliptin + pioglitazone for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2022; 23 (1): 29–42. DOI: https://doi.org/10.1080/14656566.2021.1985465 PMID: 34591742.