Clar, C., Royle, Pamela and Waugh, Norman. (2009) Adding pioglitazone to insulin containing regimens in type 2 diabetes : systematic review and meta-analysis. PLoS One, Vol.4 (No.7). e6112. ISSN 1932-6203

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Abstract

Background Type 2 diabetes is treated in a stepwise manner, progressing from diet and physical activity to oral antidiabetic agents and insulin. The oral agent pioglitazone is licensed for use with insulin when metformin is contraindicated or not tolerated. This systematic review and meta-analysis investigates the extent to which adding pioglitazone to insulin-containing regimens produces benefits in terms of patient-relevant outcomes. Methodology/Principal Findings Medline, Embase, and the Cochrane Library were searched for randomised controlled trials comparing pioglitazone in combination with any insulin-containing regimen in comparison with the same insulin regimen alone in patients with type 2 diabetes. Outcomes investigated included HbA1c, hypoglycaemia, weight, and adverse events. Studies were selected, assessed and summarised according to standard systematic review methodology and in a meta-analysis. We included eight trials that examined the benefits of adding pioglitazone to an insulin regimen and studied a total of 3092 patients with type 2 diabetes. All studies included patients with previously inadequate glucose control. Trial duration was between 12 weeks and 34.5 months. The trials used pioglitazone doses of up to 45 mg/day. In our meta-analysis, the mean reduction in HbA1c was 0.58% (95% CI: −0.70, −0.46, p<0.00001). Hypoglycaemic episodes were slightly more frequent in the pioglitazone arms (relative risk 1.27; 95% CI: 0.99, 1.63, p = 0.06). Where reported, HDL-cholesterol tended to be increased with pioglitazone. Patients on pioglitazone tended to gain more weight than those who were not, with an average difference of almost 3 kg. Peripheral oedema was more frequent in the pioglitazone groups. None of the studies reported on fractures in women, and data on cardiovascular events were inconclusive, with most studies being too short or too small to assess these long-term outcomes. Conclusions/Significance When added to insulin regimens, pioglitazone confers a small advantage in terms of HbA1c in type 2 diabetes patients with previous inadequate glucose control, but at the cost of increased hypoglycaemia and weight gain. Other considerations include the risk of heart failure, fractures in women, a reduced insulin dose, and the net financial cost.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Health Sciences
Library of Congress Subject Headings (LCSH):	Non-insulin-dependent diabetes -- Treatment, Hypoglycemic agents
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Date:	1 July 2009
Volume:	Vol.4
Number:	No.7
Page Range:	e6112
Identification Number:	10.1371/journal.pone.0006112
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Great Britain. Dept. of Health (DoH), NIHR Health Technology Assessment Programme (Great Britain)
References:	1. DeFronzo RA (1999) Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 131: 281–303. 2. UKPDS Study Group (1988) UK Prospective Diabetes Study. V. Characteristics of newly presenting type 2 diabetic patients: estimated insulin sensitivity and islet 4-cell function. Multi-centre study. Diabet Med 5: 444–448. 3. Turner R, Cull C, Holman R (1996) UK Prospective Diabetes Study 17: a 9- year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med 124: 136–145. 4. UKPDS Study Group (1995) UKPDS 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes 44: 1249–1258. 5. National Collaborating Centre for Chronic Conditions (2008) Type 2 diabetes: national clinical guideline for management in primary and secondary care (update). 6. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, et al. (2009) Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy. Diabetologia 52: 17–30. 7. The Information Centre and Yorkshire and Humber Public Health Observatory (2007) Prescribing for Diabetes in England: An analysis of volume, expenditure and trends. http://www.yhpho.org.uk/Download/Public/1265/1/Prescribing% 20for%20Diabetes%20in%20England%20Nov%202007%20FINAL.pdf. 8. European Medicines Agency (2007) Actos: European Public Assessment Report. http://www.emea.europa.eu/humandocs/Humans/EPAR/actos/actos.htm. 9. Richter B, Bandeira-Echtler E, Bergerhoff K, Clar C, Ebrahim SH (2006) Pioglitazone for type 2 diabetes mellitus. Cochrane Database Syst Rev CD006060. 10. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, 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: 1279–1289. 11. Erdmann E, Charbonnel B, Wilcox RG, Skene AM, Massi-Benedetti M, et al. (2007) Pioglitazone use and heart failure in patients with type 2 diabetes and preexisting cardiovascular disease: data from the PROactive study (PROactive 08). Diabetes Care 30: 2773–2778. 12. Strowig SM, Raskin P (2005) Combination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitus. Diabetes Obes Metab 7: 633–641. 13. Bailey CJ (2005) Treating insulin resistance in type 2 diabetes with metformin and thiazolidinediones. Diabetes Obes Metab 7: 675–691. 14. National Institute for Health and Clinical Excellence (2007) The guidelines manual. London: National Institute for Health and Clinical Excellence. Available: http://www.nice.org.uk/aboutnice/howwework/developingniceclinicalguidelines/ clinicalguidelinedevelopmentmethods/GuidelinesManual2009. jsp. 15. Asnani S, Kunhiraman B, Jawa A, Akers D, Lumpkin D, et al. (2006) Pioglitazone restores endothelial function in patients with type 2 diabetes treated with insulin. Metab Syndr Relat Disord 4: 179–184. 16. Berhanu P, Perez A, Yu S (2007) 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, Obesity & Metabolism 9: 512–520. 17. Fernandez M, Triplitt C, Wajcberg E, Sriwijilkamol AA, Musi N, et al. (2008) Addition of pioglitazone and ramipril to intensive insulin therapy in type 2 diabetic patients improves vascular dysfunction by different mechanisms. Diabetes Care 31: 121–127. 18. Mattoo V, Eckland D, Widel M, Duran S, Fajardo C, et al. (2005) 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. Clinical therapeutics 27: 554–567. 19. Raz I, Stranks S, Filipczak R, Joshi P, Lertoft B, et al. (2005) 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. Clinical therapeutics 27: 1432–1443. 20. Rosenstock J (2002) Efficacy and safety of pioglitazone in type 2 diabetes: A randomised, placebo-controlled study in patients receiving stable insulin therapy. International Journal of Clinical Practice 56: 251–257. 21. Scheen A, Charbonnel B (2006) Reduced insulin requirements and improved glycemic control with pioglitazone in insulin-treated patients with type 2 diabetes: Results from PROactive. Diabetes 55: A134. 22. Shah PK, Mudahar S, Aroda V, Wilson J, Chao E, et al. (2007) Weight gain and fat distribution with pioglitazone in patients with type 2 diabetes on insulin therapy. Journal of Investigative Medicine 55 (Suppl.S): S95. 23. Davidson J, Vexiau P, Cucinotta D, Vaz J, Kawamori R (2005) Biphasic insulin aspart 30: literature review of adverse events associated with treatment. Clin Ther 27 Suppl B: S75–S88. 24. Nissen SE, Wolski K (2007) Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 356: 2457–2471. 25. Monami M, Marchionni N, Mannucci E (2008) Winners and losers at the rosiglitazone gamble A meta-analytical approach at the definition of the cardiovascular risk profile of rosiglitazone. Diabetes Res Clin Pract 82: 48–57. 26. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE (2007) Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA 298: 1180–1188. 27. Mannucci E, Monami M, Lamanna C, Gensini GF, Marchionni N (2008) Pioglitazone and cardiovascular risk. A comprehensive meta-analysis of randomized clinical trials. Diabetes Obes Metab 10: 1221–1238. 28. Berneis K, Rizzo M, Stettler C, Chappuis B, Braun M, et al. (2008) Comparative effects of rosiglitazone and pioglitazone on fasting and postprandial low-density lipoprotein size and subclasses in patients with Type 2 diabetes. Expert Opinion on Pharmacotherapy 9: 343–349. 29. Chappuis B, Braun M, Stettler C, Allemann S, Diem P, et al. (2007) Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study. Diabetes/Metabolism Research Reviews 23: 392–399. 30. Deeg MA, Buse JB, Goldberg RB, Kendall DM, Zagar AJ, et al. (2007) Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia. Diabetes Care 30: 2458–2464. 31. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, et al. (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355: 2427–2443. 32. Meier C, Kraenzlin ME, Bodmer M, Jick SS, Jick H, et al. (2008) Use of thiazolidinediones and fracture risk. Arch Intern Med 168: 820–825. 33. Schwartz AV (2008) TZDs and Bone: A Review of the Recent Clinical Evidence. PPAR Res. pp 297893. 34. Takeda Pharmaceuticals (2007) Observation of an increased incidence of fractures in female patients who received long-term treatment with ACTOS (pioglitazone HCI) tablets for type 2 diabetes mellitus. 35. Donnan PT, MacDonald TM, Morris AD (2002) Adherence to prescribed oral hypoglycaemic medication in a population of patients with Type 2 diabetes: a retrospective cohort study.[see comment]. Diabetic Medicine 19: 279–284. 36. Odegard PS, Capoccia K (2007) Medication taking and diabetes: a systematic review of the literature. Diabetes Educ 33: 1014–1029. 37. Morris AD (2001) The reality of Type 2 diabetes treatment today. International Journal of Clinical Practice, Supplement. pp 32–35.
URI:	http://wrap.warwick.ac.uk/id/eprint/45130

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