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Published in: Acta Diabetologica 6/2017

01-06-2017 | Original Article

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

Authors: Yu-Hung Chang, Der-Wei Hwu, Dao-Ming Chang, Ling-Wang An, Chang-Hsun Hsieh, Yau-Jiunn Lee

Published in: Acta Diabetologica | Issue 6/2017

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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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Literature
1.
go back to reference 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):773–795CrossRefPubMedPubMedCentral 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):773–795CrossRefPubMedPubMedCentral
2.
go back to reference 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):170–175CrossRefPubMed 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):170–175CrossRefPubMed
3.
go back to reference 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):1577–1596CrossRefPubMed 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):1577–1596CrossRefPubMed
4.
go back to reference 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):166–169CrossRefPubMed 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):166–169CrossRefPubMed
5.
go back to reference 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):140–149CrossRefPubMed 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):140–149CrossRefPubMed
6.
go back to reference 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):e62–74PubMedPubMedCentral 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):e62–74PubMedPubMedCentral
7.
go back to reference 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):672–679CrossRefPubMed 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):672–679CrossRefPubMed
8.
go back to reference 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):64–71CrossRefPubMed 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):64–71CrossRefPubMed
9.
10.
go back to reference 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):557–564CrossRefPubMed 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):557–564CrossRefPubMed
12.
go back to reference 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 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
13.
go back to reference 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 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.
go back to reference American Diabetes A (2013) Standards of medical care in diabetes-2013. Diabetes Care 36(Suppl 1):S11–66CrossRef American Diabetes A (2013) Standards of medical care in diabetes-2013. Diabetes Care 36(Suppl 1):S11–66CrossRef
15.
go back to reference 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):401–409CrossRefPubMed 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):401–409CrossRefPubMed
16.
go back to reference 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):1666–1674CrossRef 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):1666–1674CrossRef
17.
go back to reference 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):469–477CrossRefPubMed 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):469–477CrossRefPubMed
18.
go back to reference 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 448:232–237CrossRefPubMed 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 448:232–237CrossRefPubMed
19.
go back to reference 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):819–822CrossRefPubMed 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):819–822CrossRefPubMed
20.
go back to reference 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 730:51–60CrossRefPubMed 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 730:51–60CrossRefPubMed
21.
go back to reference 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):301–305CrossRefPubMed 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):301–305CrossRefPubMed
22.
go back to reference 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):2169–2181CrossRefPubMedPubMedCentral 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):2169–2181CrossRefPubMedPubMedCentral
23.
go back to reference 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):2153–2163CrossRefPubMed 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):2153–2163CrossRefPubMed
24.
go back to reference 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):203–211CrossRefPubMed 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):203–211CrossRefPubMed
25.
go back to reference 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):22–32CrossRefPubMed 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):22–32CrossRefPubMed
26.
go back to reference 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):1279–1289CrossRefPubMed 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):1279–1289CrossRefPubMed
27.
go back to reference 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):182–187CrossRefPubMedPubMedCentral 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):182–187CrossRefPubMedPubMedCentral
28.
go back to reference Pugliese G (2014) Updating the natural history of diabetic nephropathy. Acta Diabetol 51(6):905–915CrossRefPubMed Pugliese G (2014) Updating the natural history of diabetic nephropathy. Acta Diabetol 51(6):905–915CrossRefPubMed
29.
go back to reference 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):3543–3549CrossRefPubMed 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):3543–3549CrossRefPubMed
30.
go back to reference 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):512–524CrossRefPubMed 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):512–524CrossRefPubMed
31.
go back to reference 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):2784–2791CrossRefPubMed 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):2784–2791CrossRefPubMed
32.
go back to reference 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):2278–2287CrossRefPubMed 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):2278–2287CrossRefPubMed
33.
go back to reference 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):1933–1946CrossRefPubMed 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):1933–1946CrossRefPubMed
34.
go back to reference 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):338–345CrossRefPubMed 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):338–345CrossRefPubMed
Metadata
Title
Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus
Authors
Yu-Hung Chang
Der-Wei Hwu
Dao-Ming Chang
Ling-Wang An
Chang-Hsun Hsieh
Yau-Jiunn Lee
Publication date
01-06-2017
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 6/2017
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-017-0983-0

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