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Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus

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Abstract

Aims

Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed.

Methods

Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included.

Results

A total of 1002 patients were enrolled (pioglitazone: 559, detemir: 264, glargine: 179). After propensity score matching, there were 105 patients with matchable baseline characteristics in each group. After a mean of 3.5 years of follow-up, the pioglitazone group showed a greater HbA1c reduction than the detemir group and the glargine group. Despite patients in all three groups exhibiting significant body weight gain, those in the pioglitazone group and the glargine group showed greater body weight increases than the patients in the detemir group (2.1, 1.6 and 0.8 kg, respectively, p < 0.05). Interestingly, Cox regression analysis indicated that patients under detemir or glargine treatment had a higher probability of CKD progression as compared with the pioglitazone group, with hazard ratios of 2.63 (95% CI 1.79–3.88) and 3.13 (95% CI 2.01–4.87), respectively.

Conclusions

Our study first showed that treatment with both pioglitazone and basal insulin improved glycemic control, while only pioglitazone treatment was observed to be advantageous in terms of preserving renal function when used as an add-on therapy for patients with type 2 DM in whom sulfonylurea and metformin regimens failed.

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References

  1. Defronzo RA (2009) Banting lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58(4):773–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Genuth S (2015) Should sulfonylureas remain an acceptable first-line add-on to metformin therapy in patients with type 2 diabetes? No, it’s time to move on! Diabetes Care 38(1):170–175

    Article  CAS  PubMed  Google Scholar 

  3. Inzucchi SE, Bergenstal RM, Buse JB et al (2012) Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 55(6):1577–1596

    Article  CAS  PubMed  Google Scholar 

  4. Abrahamson MJ (2015) Should sulfonylureas remain an acceptable first-line add-on to metformin therapy in patients with type 2 diabetes? Yes, they continue to serve us well! Diabetes Care 38(1):166–169

    Article  CAS  PubMed  Google Scholar 

  5. Inzucchi SE, Bergenstal RM, Buse JB et al (2015) Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38(1):140–149

    Article  PubMed  Google Scholar 

  6. McIntosh B, Cameron C, Singh SR, Yu C, Dolovich L, Houlden R (2012) Choice of therapy in patients with type 2 diabetes inadequately controlled with metformin and a sulphonylurea: a systematic review and mixed-treatment comparison meta-analysis. Open Med 6(2):e62–74

    PubMed  PubMed Central  Google Scholar 

  7. Gross JL, Kramer CK, Leitao CB et al (2011) Effect of antihyperglycemic agents added to metformin and a sulfonylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis. Ann Intern Med 154(10):672–679

    Article  PubMed  Google Scholar 

  8. August P, Hardison RM, Hage FG et al (2014) Change in albuminuria and eGFR following insulin sensitization therapy versus insulin provision therapy in the BARI 2D study. Clin J Am Soc Nephrol 9(1):64–71

    Article  CAS  PubMed  Google Scholar 

  9. Swinnen SG, Simon AC, Holleman F, Hoekstra JB, Devries JH (2011) Insulin detemir versus insulin glargine for type 2 diabetes mellitus. Cochrane Database Syst Rev (7):CD006383. doi:10.1002/14651858.CD006383.pub2

  10. Chang YH, Lei CC, Lin KC, Chang DM, Hsieh CH, Lee YJ (2016) Serum uric acid level as an indicator for CKD regression and progression in patients with type 2 diabetes mellitus-a 4.6-year cohort study. Diabetes Metab Res Rev 32(6):557–564

    Article  CAS  PubMed  Google Scholar 

  11. Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612

    Article  PubMed  PubMed Central  Google Scholar 

  12. National Kidney F (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39(2 Suppl 1):S1–266

    Google Scholar 

  13. Kirsztajn GM, Suassuna JH, Bastos MG (2009) Dividing stage 3 of chronic kidney disease (CKD): 3A and 3B. Kidney Int 76(4):462–463; author reply 463–464

  14. American Diabetes A (2013) Standards of medical care in diabetes-2013. Diabetes Care 36(Suppl 1):S11–66

    Article  Google Scholar 

  15. Rassen JA, Shelat AA, Franklin JM, Glynn RJ, Solomon DH, Schneeweiss S (2013) Matching by propensity score in cohort studies with three treatment groups. Epidemiology 24(3):401–409

    Article  PubMed  Google Scholar 

  16. Koppe L, Pelletier CC, Alix PM et al (2014) Insulin resistance in chronic kidney disease: new lessons from experimental models. Nephrol Dial Transpl 29(9):1666–1674

    Article  CAS  Google Scholar 

  17. Chen J, Muntner P, Hamm LL et al (2003) Insulin resistance and risk of chronic kidney disease in nondiabetic US adults. J Am Soc Nephrol 14(2):469–477

    Article  CAS  PubMed  Google Scholar 

  18. Jing C, Xu S, Ming J et al (2015) Insulin resistance is not independently associated with chronic kidney disease in Chinese population: a population-based cross-sectional study. Clin Chim Acta 448:232–237

    Article  CAS  PubMed  Google Scholar 

  19. Peng XH, Liang PY, Ou SJ, Zu XB (2014) Protective effect of pioglitazone on kidney injury in diabetic rats. Asian Pac J Trop Med 7(10):819–822

    Article  CAS  PubMed  Google Scholar 

  20. Ochodnicky P, Mesarosova L, Cernecka H et al (2014) Pioglitazone, a PPARgamma agonist, provides comparable protection to angiotensin converting enzyme inhibitor ramipril against adriamycin nephropathy in rat. Eur J Pharmacol 730:51–60

    Article  CAS  PubMed  Google Scholar 

  21. Fernandez-Real JM, Vendrell J, Garcia I, Ricart W, Valles M (2012) Structural damage in diabetic nephropathy is associated with TNF-alpha system activity. Acta Diabetol 49(4):301–305

    Article  CAS  PubMed  Google Scholar 

  22. Monroy A, Kamath S, Chavez AO et al (2009) Impaired regulation of the TNF-alpha converting enzyme/tissue inhibitor of metalloproteinase 3 proteolytic system in skeletal muscle of obese type 2 diabetic patients: a new mechanism of insulin resistance in humans. Diabetologia 52(10):2169–2181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tripathy D, Daniele G, Fiorentino TV et al (2013) Pioglitazone improves glucose metabolism and modulates skeletal muscle TIMP-3-TACE dyad in type 2 diabetes mellitus: a randomised, double-blind, placebo-controlled, mechanistic study. Diabetologia 56(10):2153–2163

    Article  CAS  PubMed  Google Scholar 

  24. Jin HM, Pan Y (2007) Renoprotection provided by losartan in combination with pioglitazone is superior to renoprotection provided by losartan alone in patients with type 2 diabetic nephropathy. Kidney Blood Press Res 30(4):203–211

    Article  CAS  PubMed  Google Scholar 

  25. Petrica L, Vlad A, Petrica M et al (2011) Pioglitazone delays proximal tubule dysfunction and improves cerebral vessel endothelial dysfunction in normoalbuminuric people with type 2 diabetes mellitus. Diabetes Res Clin Pract 94(1):22–32

    Article  CAS  PubMed  Google Scholar 

  26. Dormandy JA, Charbonnel B, Eckland DJ et al (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366(9493):1279–1289

    Article  CAS  PubMed  Google Scholar 

  27. Schneider CA, Ferrannini E, Defronzo R, Schernthaner G, Yates J, Erdmann E (2008) Effect of pioglitazone on cardiovascular outcome in diabetes and chronic kidney disease. J Am Soc Nephrol 19(1):182–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pugliese G (2014) Updating the natural history of diabetic nephropathy. Acta Diabetol 51(6):905–915

    Article  CAS  PubMed  Google Scholar 

  29. Chan DT, Watts GF, Irish AB, Dogra GK (2011) Rosiglitazone does not improve vascular function in subjects with chronic kidney disease. Nephrol Dial Transplant 26(11):3543–3549

    Article  CAS  PubMed  Google Scholar 

  30. Davies MJ, Gagliardino JJ, Gray LJ, Khunti K, Mohan V, Hughes R (2013) Real-world factors affecting adherence to insulin therapy in patients with Type 1 or Type 2 diabetes mellitus: a systematic review. Diabet Med 30(5):512–524

    Article  CAS  PubMed  Google Scholar 

  31. Miyazaki Y, Mahankali A, Matsuda M et al (2002) Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 87(6):2784–2791

    Article  CAS  PubMed  Google Scholar 

  32. Russo GT, De Cosmo S, Viazzi F et al (2016) Plasma triglycerides and HDL-C levels predict the development of diabetic kidney disease in subjects with type 2 diabetes: the AMD annals initiative. Diabetes Care 39(12):2278–2287

    Article  PubMed  Google Scholar 

  33. Brod M, Rana A, Barnett AH (2012) Adherence patterns in patients with type 2 diabetes on basal insulin analogues: missed, mistimed and reduced doses. Curr Med Res Opin 28(12):1933–1946

    Article  CAS  PubMed  Google Scholar 

  34. Farsaei S, Radfar M, Heydari Z, Abbasi F, Qorbani M (2014) Insulin adherence in patients with diabetes: risk factors for injection omission. Prim Care Diabetes 8(4):338–345

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Felix Thoemmes, Department of Human Development, Cornell University, Ithaca, NY, for the development of the propensity score matching program for SPSS.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Author contributions

YHC and DWH contributed to the acquisition, analysis, interpretation of the data and the development of the manuscript. DMC contributed to the acquisition and analysis of the data. ALW and CHH contributed to the discussion. YJL contributed to the discussion and reviewed/edited the manuscript.

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Author notes

    Authors and Affiliations

    1. Department of Internal Medicine, Lee’s Endocrinology Clinic, # 130 Min-Tzu Rd, Pingtung, 90000, Taiwan

      Yu-Hung Chang, Der-Wei Hwu, Dao-Ming Chang & Yau-Jiunn Lee

    2. Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

      Der-Wei Hwu

    3. Department of Medical Education, Beijing Ruijing Diabetes Hospital, Beijing, 100078, China

      Ling-Wang An

    4. Division of Endocrinology and Metabolism, Department of Internal MedicineNational Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan

      Chang-Hsun Hsieh

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    1. Yu-Hung Chang
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    Correspondence to Yu-Hung Chang.

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    Conflicts of interest

    Y.-H. Chang, D.-M. Chang and Y.-J. Lee received speaking fees from NovoNordisk and Sanofi.

    Human and animal rights disclosure

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of Tri-Service General Hospital and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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    Formal consent is not required for this retrospective study.

    Data availability statements

    The datasets during and/or analyzed during the current study available from the corresponding author on reasonable request.

    Additional information

    Managed by Massimo Porta.

    Yu-Hung Chang and Der-Wei Hwu contributed equally.

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    Supplementary material 1 (DOCX 22 kb)

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    Chang, YH., Hwu, DW., Chang, DM. et al. Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus. Acta Diabetol 54, 561–568 (2017). https://doi.org/10.1007/s00592-017-0983-0

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    • DOI: https://doi.org/10.1007/s00592-017-0983-0

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