The Efficacy of Adding Pioglitazone to Insulin Therapy in Type 2 Diabetes: A Systematic Review and Meta-analysis
-
Majid Davari
,
Elahe Khorasani
,
Rahim Sarvari Shojaei
,
Ali Akbari Sari
,
Hamidreza Zakeri
,
Parisa Saiyarsarai
Abstract
Objectives: The significant increase of type 2 diabetes and its complications in individuals requires developing new approaches to control this disease. The present study aimed to evaluate the efficacy of pioglitazone and insulin combination therapy, compared to insulin therapy in patients with type 2 diabetes. Methods: Medline, Cochrane Library, and Embase were searched for Randomized Controlled Trials (RCTs) comparing pioglitazone in combination with any insulin-containing regimen and the same insulin regimen alone in patients with type 2 diabetes. Hand searching was conducted in journals, congresses, and RCT registration databases related to diabetes. There were no restrictions on the language and publication year of articles. RCTs were evaluated based on the inclusion and exclusion criteria; the quality of studies was evaluated using the Jadad and the Cochrane collaboration’s tools. After evaluating and extracting the data, thecommon results of the selected papers were entered in RevMan. Furthermore, in the cases that studies were homogeneous, meta-analysis was performed; in the cases that studies were heterogeneous, the findings were reported in a qualitative form. Results: From the first found essays, 12 were elected for studying, including a total of 3208 patients with type 2 diabetes. The trial duration was between 12 weeks and 34.5 months. The study results presented a reduction in HbA1c and insulin dose in the combination therapy with pioglitazone arm. In our meta-analysis, the mean reduction in HbA1c was equal to 0.64%, i.e., significant [95% Confidence Interval (CI): -0.86 to -0.41, P<0.00001]. Conclusions: This systematic review indicated that in patients with type 2 diabetes, the addition of pioglitazone to the insulin regimen, compared to the insulin regimens, reduced HbA1c.
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[4] Lankarani M, Zahedi F. [Primary prevention of type 2 diabetes mellitus (Persian)]. Iran J Diabetes Metab. 2002; 1(2):87-106. https://ijdld.tums.ac.ir/article-1-480-en.html
[5] Horton ES. Defining the role of basal and prandial insulin for optimal glycemic control. J Am Coll Cardiol. 2009; 53(5 Suppl):S21-7. [DOI:10.1016/j.jacc.2008.11.008] [PMID]
[6] German Diabetes Association, Matthaei S, Bierwirth R, Fritsche A, Gallwitz B, Häring HU, et al. Medical antihyperglycaemic treatment of type 2 diabetes mellitus: Update of the evidence-based guideline of the German Diabetes Association. Exp Clin Endocrinol Diabetes. 2009; 117(9):522-57. [DOI:10.1055/s-0029-1239559] [PMID]
[7] Rodbard HW, Jellinger PS, Davidson JA, Einhorn D, Garber AJ, Grunberger G, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: An algorithm for glycemic control. Endocr Pract. 2009; 15(6):540-59. [DOI:10.4158/EP.15.6.540] [PMID]
[8] Yki-Järvinen H. Thiazolidinediones. N Engl J Med. 2004; 351(11):1106-18. [DOI:10.1056/NEJMra041001] [PMID]
[9] Huang A, Raskin P. Thiazolidinediones and insulin: Rationale for use and role of combination therapy in type 2 diabetes. Treat Endocrinol. 2005; 4(4):205-20. [DOI:10.2165/00024677-200504040-00002] [PMID]
[10] UK Prospective Diabetes Study (UKPDS) Group. Intensive bloodglucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352(9131):837-53. [DOI:10.1016/S0140-6736(98)07019-6] [PMID]
[11] Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes. 1996; 45(12):1661-9. [DOI:10.2337/diabetes.45.12.1661] [PMID]
[12] Davidson JA, Perez A, Zhang J, The Pioglitazone 343 Study Group. Addition of pioglitazone to stable insulin therapy in patients with poorly controlled type 2 diabetes: Results of a double‐blind, multicentre, randomized study. Diabetes Obes Metab. 2006; 8(2):164-74. [DOI:10.1111/j.1463-1326.2005.00499.x] [PMID]
[13] Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: A meta-analysis of randomised clinical trials. Lancet. 2007; 370(9593):1129-36. [DOI:10.1016/S0140-6736(07)61514-1] [PMID]
[14] Derosa G. Efficacy and tolerability of pioglitazone in patients with Type 2 Diabetes Mellitus: Comparison with other oral antihyperglycaemic agents. Drugs. 2010; 70(15):1945-61. [DOI:10.2165/11538100-000000000-00000] [PMID]
[15] Scheen AJ. Combined thiazolidinedione-insulin therapy: Should we be concerned about safety? Drug Saf. 2004; 27(12):841-56. [DOI:10.2165/00002018-200427120-00002] [PMID]
[16] Rosenstock J, Einhorn D, Hershon K, Glazer NB, Yu S, Pioglitazone 014 Study Group. Efficacy and safety of pioglitazone in type 2 diabetes: A randomised, placebo-controlled study in patients receiving stable insulin therapy. Int J Clin Pract. 2002; 56(4):251-7. [PMID]
[17] Schwartz AV, Sellmeyer DE, Vittinghoff E, Palermo L, Lecka-Czernik B, Feingold KR, et al. Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab. 2006; 91(9):3349-54. [DOI:10.1210/jc.2005-2226] [PMID] [PMCID]
[18] Berhanu P, Perez A, Yu S. Effect of pioglitazone in combination with insulin therapy on glycaemic control, insulin dose requirement and lipid profile in patients with type 2 diabetes previously poorly controlled with combination therapy. Diabetes Obes Metab. 2007; 9(4):512-20. [DOI:10.1111/j.1463-1326.2006.00633.x] [PMID]
[19] Scheen A, Charbonnel B. Reduced insulin requirements and improved glycemic control with pioglitazone in insulin-treated patients with type 2 diabetes: Results from PROactive. Diabetes. 2006; 55(Suppl 1):A134. https://scholar.google.co/scholar?q=Reduced+insulin+requirements+and+improved+glycemic+control+with+piog
litazone+in+insulin-treated+patients+with+type+2+diabetes:+results+from+PROactive.&hl=fa&as_sdt=0,5
[20] Raz I, Stranks S, Filipczak R, Joshi P, Lertoft B, Rastam J, et al. Efficacy and safety of biphasic insulin aspart 30 combined with pioglitazone in type 2 diabetes poorly controlled on glibenclamide (glyburide) monotherapy or combination therapy: An 18-week, randomized, open-label study. Clin Ther. 2005; 27(9):1432-43. [DOI:10.1016/j.clinthera.2005.09.001] [PMID]
[21] Tolman KG, Freston JW, Kupfer S, Perez A. Liver safety in patients with type 2 diabetes treated with pioglitazone: Results from a 3-year, randomized, comparator-controlled study in the US. Drug saf. 2009; 32(9):787-800.[DOI:10.2165/11316510-000000000-00000] [PMID]
[22] Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: A meta-analysis. CMAJ. 2009; 180(1):32-9. [DOI:10.1503/cmaj.080486] [PMID] [PMCID]
[23] Fernandez M, Triplitt C, Wajcberg E, Sriwijilkamol AA, Musi N, Cusi K, et al. Addition of pioglitazone and ramipril to intensive insulin therapy in type 2 diabetic patients improves vascular dysfunction by different mechanisms. Diabetes Care. 2008; 31(1):121-7. [DOI:10.2337/dc07-0711] [PMID]
[24] Asnani S, Kunhiraman B, Jawa A, Akers D, Lumpkin D, Fonseca V. Pioglitazone restores endothelial function in patients with type 2 diabetes treated with insulin. Metab Syndr Relat Disord. 2006; 4(3):179-84. [DOI:10.1089/met.2006.4.179] [PMID]
[25] Galle J, Kleophas W, Dellanna F, Schmid VHR, Forkel C, Dikta G, et al. Comparison of the effects of pioglitazone versus placebo when given in addition to standard insulin treatment in patients with type 2 diabetes mellitus requiring Hemodialysis: Results from the PIOren Study. Nephron Extra. 2012; 2(1):104-14. [DOI:10.1159/000337334]
[PMID] [PMCID]
[26] Yasunari E, Takeno K, Funayama H, Tomioka S, Tamaki M, Fujitani Y, et al. Efficacy of pioglitazone on glycemic control and carotid intima‐media thickness in type 2 diabetes patients with inadequate insulin therapy. J Diabetes Investig. 2011; 2(1):56-62. [DOI:10.1111/j.2040-1124.2010.00064.x] [PMID] [PMCID]
[27] Lamarche B, St-Pierre AC, Ruel IL, Cantin B, Dagenais GR, Després J-P. A prospective, population-based study of low density lipoprotein particle size as a risk factor for ischemic heart disease in men. Can J Cardiol. 2001; 17(8):859-65. [PMID]
[28] Shah PK, Mudaliar S, Aroda V, Wilson J, Chao E, Chang A, et al. 113 weight gain and fat distribution with pioglitazone in patients with type 2 diabetes on insulin therapy. J Investig Med. 2007; 55(1):S95.
https://jim.bmj.com/content/55/1/S95.3.citation-tools
[29] Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis of randomized trials. JAMA. 2007; 298(10):1180-8. [DOI:10.1001/jama.298.10.1180] [PMID]
[30] Mudaliar S, Chang AR, Aroda VR, Chao E, Burke P, Baxi S, et al. Effects of intensive insulin therapy alone and with added pioglitazone on renal salt/water balance and fluid compartment shifts in type 2 diabetes. Diabetes Obes Metab. 2010; 12(2):133-8. [DOI:10.1111/j.1463-1326.2009.01126.x] [PMID]
[31] Henriksen K, Byrjalsen I, Qvist P, Beck‐Nielsen H, Hansen G, Riis BJ, et al. Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: A phase III, randomized, parallel‐group study in patients with type 2 diabetes on stable insulin therapy. Diabetes Metab Res Rev. 2011; 27(4):392-401. [DOI:10.1002/dmrr.1187] [PMID]
[32] Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: The PERISCOPE randomized controlled trial. JAMA. 2008; 299(13):1561-73. [DOI:10.1001/jama.299.13.1561] [PMID]
[33] Delea TE, Edelsberg JS, Hagiwara M, Oster G, Phillips LS. Use of thiazolidinediones and risk of heart failure in people with type 2 diabetes: A retrospective cohort study. Diabetes Care. 2003; 26(11):2983-9. [DOI:10.2337/diacare.26.11.2983] [PMID]
[34] Cheng AYY, Fantus IG. Thiazolidinedione-induced congestive heart failure. Ann Pharmacother. 2004; 38(5):817-20. [DOI:10.1345/ aph.1D400] [PMID]
[35] Kermani A, Garg A. Thiazolidinedione-associated congestive heart failure and pulmonary edema. Mayo Clin Proc. 2003; 78(9):1088-91. [DOI:10.4065/78.9.1088] [PMID]
[36] Pontiroli AE, Miele L, Morabito A. Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: Systematic review and meta‐analysis. Diabetes Obes Metab. 2011; 13(11):1008-19. [DOI:10.1111/j.1463-1326.2011.01433.x] [PMID]
[37] Larsen TM, Toubro S, Astrup A. PPARgamma agonists in the treatment of type II diabetes: Is increased fatness commensurate with long-term efficacy? Int J Obes Relat Metab Disord. 2003; 27(2):147-61. [DOI:10.1038/sj.ijo.802223] [PMID]
[38] Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2002; 87(6):2784-91. [DOI:10.1210/jcem.87.6.8567] [PMID]
[39] Shadid S, Jensen MD. Effects of pioglitazone versus diet and exercise on metabolic health and fat distribution in upper body obesity. Diabetes Care. 2003; 26(11):3148-52. [DOI:10.2337/diacare. 26.11.3148] [PMID]
[40] Mattoo V, Eckland D, Widel M, Duran S, Fajardo C, Strand J, et al. Metabolic effects of pioglitazone in combination with insulin in patients with type 2 diabetes mellitus whose disease is not adequately controlled with insulin therapy: Results of a six-month, randomized, double-blind, prospective, multicenter, parallel-group study. Clin Ther. 2005; 27(5):554-67. https://www.sciencedirect.com/science/article/abs/pii/S0149291805000810
[2] World Health Organization (WHO). Global report on diabetes. [Internet]. 2016 [Updated 2016 April 21]. Available from: https://www.who.int/publications/i/item/9789241565257
[3] World Health Organization (WHO). Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO consultation. Part 1, Diagnosis and classification of diabetes mellitus. [Internet]. 1999 [Updated 1999]. Available from: https://apps.who.int/iris/handle/10665/66040
[4] Lankarani M, Zahedi F. [Primary prevention of type 2 diabetes mellitus (Persian)]. Iran J Diabetes Metab. 2002; 1(2):87-106. https://ijdld.tums.ac.ir/article-1-480-en.html
[5] Horton ES. Defining the role of basal and prandial insulin for optimal glycemic control. J Am Coll Cardiol. 2009; 53(5 Suppl):S21-7. [DOI:10.1016/j.jacc.2008.11.008] [PMID]
[6] German Diabetes Association, Matthaei S, Bierwirth R, Fritsche A, Gallwitz B, Häring HU, et al. Medical antihyperglycaemic treatment of type 2 diabetes mellitus: Update of the evidence-based guideline of the German Diabetes Association. Exp Clin Endocrinol Diabetes. 2009; 117(9):522-57. [DOI:10.1055/s-0029-1239559] [PMID]
[7] Rodbard HW, Jellinger PS, Davidson JA, Einhorn D, Garber AJ, Grunberger G, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: An algorithm for glycemic control. Endocr Pract. 2009; 15(6):540-59. [DOI:10.4158/EP.15.6.540] [PMID]
[8] Yki-Järvinen H. Thiazolidinediones. N Engl J Med. 2004; 351(11):1106-18. [DOI:10.1056/NEJMra041001] [PMID]
[9] Huang A, Raskin P. Thiazolidinediones and insulin: Rationale for use and role of combination therapy in type 2 diabetes. Treat Endocrinol. 2005; 4(4):205-20. [DOI:10.2165/00024677-200504040-00002] [PMID]
[10] UK Prospective Diabetes Study (UKPDS) Group. Intensive bloodglucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352(9131):837-53. [DOI:10.1016/S0140-6736(98)07019-6] [PMID]
[11] Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes. 1996; 45(12):1661-9. [DOI:10.2337/diabetes.45.12.1661] [PMID]
[12] Davidson JA, Perez A, Zhang J, The Pioglitazone 343 Study Group. Addition of pioglitazone to stable insulin therapy in patients with poorly controlled type 2 diabetes: Results of a double‐blind, multicentre, randomized study. Diabetes Obes Metab. 2006; 8(2):164-74. [DOI:10.1111/j.1463-1326.2005.00499.x] [PMID]
[13] Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: A meta-analysis of randomised clinical trials. Lancet. 2007; 370(9593):1129-36. [DOI:10.1016/S0140-6736(07)61514-1] [PMID]
[14] Derosa G. Efficacy and tolerability of pioglitazone in patients with Type 2 Diabetes Mellitus: Comparison with other oral antihyperglycaemic agents. Drugs. 2010; 70(15):1945-61. [DOI:10.2165/11538100-000000000-00000] [PMID]
[15] Scheen AJ. Combined thiazolidinedione-insulin therapy: Should we be concerned about safety? Drug Saf. 2004; 27(12):841-56. [DOI:10.2165/00002018-200427120-00002] [PMID]
[16] Rosenstock J, Einhorn D, Hershon K, Glazer NB, Yu S, Pioglitazone 014 Study Group. Efficacy and safety of pioglitazone in type 2 diabetes: A randomised, placebo-controlled study in patients receiving stable insulin therapy. Int J Clin Pract. 2002; 56(4):251-7. [PMID]
[17] Schwartz AV, Sellmeyer DE, Vittinghoff E, Palermo L, Lecka-Czernik B, Feingold KR, et al. Thiazolidinedione use and bone loss in older diabetic adults. J Clin Endocrinol Metab. 2006; 91(9):3349-54. [DOI:10.1210/jc.2005-2226] [PMID] [PMCID]
[18] Berhanu P, Perez A, Yu S. Effect of pioglitazone in combination with insulin therapy on glycaemic control, insulin dose requirement and lipid profile in patients with type 2 diabetes previously poorly controlled with combination therapy. Diabetes Obes Metab. 2007; 9(4):512-20. [DOI:10.1111/j.1463-1326.2006.00633.x] [PMID]
[19] Scheen A, Charbonnel B. Reduced insulin requirements and improved glycemic control with pioglitazone in insulin-treated patients with type 2 diabetes: Results from PROactive. Diabetes. 2006; 55(Suppl 1):A134. https://scholar.google.co/scholar?q=Reduced+insulin+requirements+and+improved+glycemic+control+with+piog
litazone+in+insulin-treated+patients+with+type+2+diabetes:+results+from+PROactive.&hl=fa&as_sdt=0,5
[20] Raz I, Stranks S, Filipczak R, Joshi P, Lertoft B, Rastam J, et al. Efficacy and safety of biphasic insulin aspart 30 combined with pioglitazone in type 2 diabetes poorly controlled on glibenclamide (glyburide) monotherapy or combination therapy: An 18-week, randomized, open-label study. Clin Ther. 2005; 27(9):1432-43. [DOI:10.1016/j.clinthera.2005.09.001] [PMID]
[21] Tolman KG, Freston JW, Kupfer S, Perez A. Liver safety in patients with type 2 diabetes treated with pioglitazone: Results from a 3-year, randomized, comparator-controlled study in the US. Drug saf. 2009; 32(9):787-800.[DOI:10.2165/11316510-000000000-00000] [PMID]
[22] Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: A meta-analysis. CMAJ. 2009; 180(1):32-9. [DOI:10.1503/cmaj.080486] [PMID] [PMCID]
[23] Fernandez M, Triplitt C, Wajcberg E, Sriwijilkamol AA, Musi N, Cusi K, et al. Addition of pioglitazone and ramipril to intensive insulin therapy in type 2 diabetic patients improves vascular dysfunction by different mechanisms. Diabetes Care. 2008; 31(1):121-7. [DOI:10.2337/dc07-0711] [PMID]
[24] Asnani S, Kunhiraman B, Jawa A, Akers D, Lumpkin D, Fonseca V. Pioglitazone restores endothelial function in patients with type 2 diabetes treated with insulin. Metab Syndr Relat Disord. 2006; 4(3):179-84. [DOI:10.1089/met.2006.4.179] [PMID]
[25] Galle J, Kleophas W, Dellanna F, Schmid VHR, Forkel C, Dikta G, et al. Comparison of the effects of pioglitazone versus placebo when given in addition to standard insulin treatment in patients with type 2 diabetes mellitus requiring Hemodialysis: Results from the PIOren Study. Nephron Extra. 2012; 2(1):104-14. [DOI:10.1159/000337334]
[PMID] [PMCID]
[26] Yasunari E, Takeno K, Funayama H, Tomioka S, Tamaki M, Fujitani Y, et al. Efficacy of pioglitazone on glycemic control and carotid intima‐media thickness in type 2 diabetes patients with inadequate insulin therapy. J Diabetes Investig. 2011; 2(1):56-62. [DOI:10.1111/j.2040-1124.2010.00064.x] [PMID] [PMCID]
[27] Lamarche B, St-Pierre AC, Ruel IL, Cantin B, Dagenais GR, Després J-P. A prospective, population-based study of low density lipoprotein particle size as a risk factor for ischemic heart disease in men. Can J Cardiol. 2001; 17(8):859-65. [PMID]
[28] Shah PK, Mudaliar S, Aroda V, Wilson J, Chao E, Chang A, et al. 113 weight gain and fat distribution with pioglitazone in patients with type 2 diabetes on insulin therapy. J Investig Med. 2007; 55(1):S95.
https://jim.bmj.com/content/55/1/S95.3.citation-tools
[29] Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis of randomized trials. JAMA. 2007; 298(10):1180-8. [DOI:10.1001/jama.298.10.1180] [PMID]
[30] Mudaliar S, Chang AR, Aroda VR, Chao E, Burke P, Baxi S, et al. Effects of intensive insulin therapy alone and with added pioglitazone on renal salt/water balance and fluid compartment shifts in type 2 diabetes. Diabetes Obes Metab. 2010; 12(2):133-8. [DOI:10.1111/j.1463-1326.2009.01126.x] [PMID]
[31] Henriksen K, Byrjalsen I, Qvist P, Beck‐Nielsen H, Hansen G, Riis BJ, et al. Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: A phase III, randomized, parallel‐group study in patients with type 2 diabetes on stable insulin therapy. Diabetes Metab Res Rev. 2011; 27(4):392-401. [DOI:10.1002/dmrr.1187] [PMID]
[32] Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: The PERISCOPE randomized controlled trial. JAMA. 2008; 299(13):1561-73. [DOI:10.1001/jama.299.13.1561] [PMID]
[33] Delea TE, Edelsberg JS, Hagiwara M, Oster G, Phillips LS. Use of thiazolidinediones and risk of heart failure in people with type 2 diabetes: A retrospective cohort study. Diabetes Care. 2003; 26(11):2983-9. [DOI:10.2337/diacare.26.11.2983] [PMID]
[34] Cheng AYY, Fantus IG. Thiazolidinedione-induced congestive heart failure. Ann Pharmacother. 2004; 38(5):817-20. [DOI:10.1345/ aph.1D400] [PMID]
[35] Kermani A, Garg A. Thiazolidinedione-associated congestive heart failure and pulmonary edema. Mayo Clin Proc. 2003; 78(9):1088-91. [DOI:10.4065/78.9.1088] [PMID]
[36] Pontiroli AE, Miele L, Morabito A. Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: Systematic review and meta‐analysis. Diabetes Obes Metab. 2011; 13(11):1008-19. [DOI:10.1111/j.1463-1326.2011.01433.x] [PMID]
[37] Larsen TM, Toubro S, Astrup A. PPARgamma agonists in the treatment of type II diabetes: Is increased fatness commensurate with long-term efficacy? Int J Obes Relat Metab Disord. 2003; 27(2):147-61. [DOI:10.1038/sj.ijo.802223] [PMID]
[38] Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2002; 87(6):2784-91. [DOI:10.1210/jcem.87.6.8567] [PMID]
[39] Shadid S, Jensen MD. Effects of pioglitazone versus diet and exercise on metabolic health and fat distribution in upper body obesity. Diabetes Care. 2003; 26(11):3148-52. [DOI:10.2337/diacare. 26.11.3148] [PMID]
[40] Mattoo V, Eckland D, Widel M, Duran S, Fajardo C, Strand J, et al. Metabolic effects of pioglitazone in combination with insulin in patients with type 2 diabetes mellitus whose disease is not adequately controlled with insulin therapy: Results of a six-month, randomized, double-blind, prospective, multicenter, parallel-group study. Clin Ther. 2005; 27(5):554-67. https://www.sciencedirect.com/science/article/abs/pii/S0149291805000810
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| Issue | Vol 7 No 1/2 (2021) | |
| Section | Review Article(s) | |
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| Pioglitazone Insulin Type 2 diabetes HbA1c Efficacy Systematic review Meta-analysis | ||
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Davari M, Khorasani E, Sarvari Shojaei R, Akbari Sari A, Zakeri H, Saiyarsarai P. The Efficacy of Adding Pioglitazone to Insulin Therapy in Type 2 Diabetes: A Systematic Review and Meta-analysis. JPPM. 2021;7(1/2):3-18.
