Initial Sulfonylurea Use and Subsequent Insulin Therapy in Older Subjects with Type 2 Diabetes Mellitus

Diabetes Therapy - Tập 3 - Trang 1-9 - 2012
Alex Z. Fu1, Ying Qiu2, Michael J. Davies2, Samuel S. Engel2
1Georgetown University Medical Center, Washington, DC, USA
2Merck Sharp & Dohme Corp, Whitehouse Station, USA

Tóm tắt

In type 2 diabetes mellitus (T2DM), progressive loss of beta cell function over time requires treatment intensification and eventually initiation of insulin for many patients. Relative to metformin, a greater rate of decline in beta cell function over time has been observed with sulfonylurea treatment. The present study examined the association between initial monotherapy with metformin or sulfonylurea and subsequent initiation of insulin in older subjects with T2DM. In a retrospective cohort study using the GE electronic medical record database, eligible subjects with T2DM included those ≥65 years who received their first prescription of sulfonylurea or metformin as initial monotherapy between January 1, 2003 to December 31, 2008. The follow-up period lasted to the end of 2009 or the subject’s latest data available. Insulin initiation was determined by prescription records. Logistic regression analysis evaluated the likelihood of insulin addition. A Cox regression model estimated time to initiation of insulin. Differences in baseline characteristics were controlled for using propensity score matching. Overall, 12,036 subjects were included in the analysis. Mean age was 75 years and 50% were male. Subjects who initiated with sulfonylurea had a significantly (P < 0.001) higher incidence of insulin addition (2.8% vs. 1.4%) compared to those initiated with metformin within 1 year of follow-up. The likelihood of initiating insulin was higher in subjects initiated with sulfonylurea than with metformin (adjusted odds ratio 1.82, 95% confidence interval [CI] 1.40–2.38; P < 0.001). Sulfonylurea use was also significantly associated with a shorter time to insulin use compared to metformin (adjusted hazards ratio 2.10, 95% CI 1.83–2.39; P < 0.001). In a cohort of older subjects with T2DM initiating antihyperglycemic therapy, new users of sulfonylurea monotherapy were more likely to receive insulin therapy and received it earlier than those starting with metformin.

Tài liệu tham khảo

UK Prospective Diabetes Atudy 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes. 1995;44:1249–58. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999;281:2005–12. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA. 2002;287:360–72. Kahn SE, Haffner SM, Heise MA, ADOPT Study Group, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427–43. Kahn SE, Lachin JM, Zinman B, ADOPT Study Group, et al. Effects of rosiglitazone, glyburide, and metformin on beta-cell function and insulin sensitivity in ADOPT. Diabetes. 2011;60:1552–60. Gong Z, Muzumdar RH. Pancreatic function, type 2 diabetes, and metabolism in aging. Int J Endocrinol. 2012;2012:320482. Zhang Q, Rajagopalan S, Marrett E, Davies MJ, Radican L, Engel SS. Time to treatment initiation with oral antihyperglycaemic therapy in US patients with newly diagnosed type 2 diabetes. Diabetes Obes Metab. 2012;14:149–54. Sinclair AJ, Alexander CM, Davies MJ, Zhao C, Mavros P. Factors associated with initiation of antihyperglycaemic medication in UK patients with newly diagnosed type 2 diabetes. BMC Endocr Disord. 2012;12:1. Riedel AA, Heien H, Wogen J, Plauschinat CA. Loss of glycemic control in patients with type 2 diabetes mellitus who were receiving initial metformin, sulfonylurea, or thiazolidinedione monotherapy. Pharmacotherapy. 2007;27:1102–10. Lobo FS, Wagner S, Gross CR, Schommer JC. Addressing the issue of channeling bias in observational studies with propensity scores analysis. Res Social Adm Pharm. 2006;2:143–51. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55. Parsons LS. Reducing bias in a propensity score matched-pair sample using greedy matching techniques (paper 214–26). Paper presented at: SUGI 26 Proceedings (Proceedings of the 26th annual SAS users group international conference), Long Beach, CA, April 22–25, 2001; Cary, NC. Perez N, Moisan J, Sirois C, Poirier P, Gregoire JP. Initiation of insulin therapy in elderly patients taking oral antidiabetes drugs. Can Med Assoc J. 2009;180:1310–6. Ringborg A, Lindgren P, Yin DD, Martinell M, Stalhammar J. Time to insulin treatment and factors associated with insulin prescription in Swedish patients with type 2 diabetes. Diabetes Metab. 2010;36:198–203. Kostev K, Dippel FW. Predictors for the initiation of a basal supported oral therapy (BOT) in type 2 diabetic patients under real-life conditions in Germany. Prim Care Diabetes. 2012 (Epub ahead of print). Donnan PT, Steinke DT, Newton RW, Morris AD. Changes in treatment after the start of oral hypoglycaemic therapy in type 2 diabetes: a population-based study. Diabet Med. 2002;19:606–10. Eurich DT, Simpson SH, Majumdar SR, Johnson JA. Secondary failure rates associated with metformin and sulfonylurea therapy for type 2 diabetes mellitus. Pharmacotherapy. 2005;25:810–6. Cook MN, Girman CJ, Stein PP, Alexander CM. Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with type 2 diabetes in UK primary care. Diabet Med. 2007;24:350–8. Rustenbeck I. Desensitization of insulin secretion. Biochem Pharmacol. 2002;63:1921–35. Maedler K, Carr RD, Bosco D, Zuellig RA, Berney T, Donath MY. Sulfonylurea induced beta-cell apoptosis in cultured human islets. J Clin Endocrinol Metab. 2005;90:501–6. Takahashi A, Nagashima K, Hamasaki A, et al. Sulfonylurea and glinide reduce insulin content, functional expression of K(ATP) channels, and accelerate apoptotic beta-cell death in the chronic phase. Diabetes Res Clin Pract. 2007;77:343–50. Kim JY, Lim DM, Park HS, et al. Exendin-4 protects against sulfonylurea-induced beta-cell apoptosis. J Pharmacol Sci. 2012;118:65–74. Satoh J, Takahashi K, Takizawa Y, et al. Secondary sulfonylurea failure: comparison of period until insulin treatment between diabetic patients treated with gliclazide and glibenclamide. Diabetes Res Clin Pract. 2005;70:291–7.