Comparison of Pioglitazone and Gliclazide in Sustaining Glycemic Control Over 2 Years in Patients With Type 2 Diabetes

Abstract

FOR THE GLAL STUDY GROUPOBJECTIVE -The hypothesis that pioglitazone treatment is superior to gliclazide treatment in sustaining glycemic control for up to 2 years in patients with type 2 diabetes was tested.RESEARCH DESIGN AND METHODS -This was a randomized, multicenter, double-blind, double-dummy, parallel-group, 2-year study. Approximately 600 patients from 98 centers participated. Eligible patients had completed a previous 12-month study and consented to continue treatment for a further year. To avoid selection bias, all patients from all centers were included in the primary analysis (a comparison of the time-to-failure distributions of the two groups by using a log-rank test) regardless of whether they continued treatment for a 2nd year. By using repeated-measures ANOVA, time course of least square means of HbA 1c and homeostasis model of assessment (HOMA) indexes (HOMA-%S and HOMA-%B) were analyzed.RESULTS -A greater proportion of patients treated with pioglitazone maintained HbA 1c Ͻ8% over the 2-year period than those treated with gliclazide. A difference between the KaplanMeier curves was apparent as early as week 32 and widened at each time point thereafter, becoming statistically significant from week 52 onward. At week 104, 129 (47.8%) of 270 pioglitazone-treated patients and 110 (37.0%) of 297 gliclazide-treated patients maintained HbA 1c Ͻ8%. Compared with gliclazide treatment, pioglitazone treatment produced a larger decrease in HbA 1c , a larger increase in HOMA-%S, and a smaller increase in HOMA-%B during the 2nd year of treatment.CONCLUSIONS -Pioglitazone is superior to gliclazide in sustaining glycemic control in patients with type 2 diabetes during the 2nd year of treatment. Diabetes Care 28:544 -550, 2005T ype 2 diabetes, with its core defects of insulin resistance and relative insulin deficiency, is a progressive disease. Insulin resistance remains generally stable throughout the natural history of the disease, but there is a progressive loss of glycemic control due to the continuing loss of ␤-cell function. The U.K. Prospective Diabetes Study (1) showed that at diagnosis, patients have already lost ϳ50% of their ␤-cell function, which was further reduced to ϳ30% at 5 years.The standard approach at initial diagnosis for many patients with type 2 diabetes is a prescription of diet and physical activity to correct their hyperglycemia. When glycemic targets cannot be attained or maintained with this approach, an oral antihyperglycemic medication (OAM) is added to the lifestyle regimen. When monotherapy fails, treatment is changed to combination OAM therapy, OAMs plus insulin, or insulin therapy (2). Most patients initially respond to OAM monotherapy when they use it. However, with continued therapy, some patients can no longer achieve their glycemic target. The inability to maintain the glycemic target may indicate progression of disease rather than lack of response to a drug (3,4).Sulfonylureas, first introduced in the mid-1950s, are commonly used as monotherapy in patients with type 2 diabete...

Evidence-Based Practice Use of Incretin-Based Therapy in the Natural History of Diabetes

“…152 The results can be contrasted to the marked monotherapy failure rates observed with sulfonylureas after 1 year of use. [153][154][155][156][157][158] Many commentators contrast the low cost of individual doses of sulfonylureas with the higher cost of incretin classes of drugs, however, focusing solely on drug costs fails to recognize the greater expenses associated with older medications for increased patient emergency room visits, hospitalizations, mortality, under-recognized hypoglycemic unawareness, lifestyle restrictions, and self-monitoring of blood glucose testing, as well as diminished quality of life, worry for spouse, friends, and coworkers, fear of hypoglycemia leading to inadequate glycemic control, and severe hypoglycemia increasing the risk of dementia. [159][160][161] In addition, given increased apoptosis (death) of β-cells with sulfonylurea use, patients will need more expensive drugs in 1 to 3 years, but with the disadvantage of having lost β-cell mass.…”

New oral antidiabetic agents

“…Glitazones increase nonoxidative glucose disposal, increase triglyceride synthesis, and improve free fatty acid metabolism [2]. They have similar glucose-lowering effects as all the others commonly used oral agents (generally reducing A1C levels by 1-2%), but they can maintain stable blood glucose control over periods of 2 years [3,4]. This durability in blood glucose control has been attributed to an improvement in b-cell secretory function over time [5,6].…”

Thiazolidinediones and Type 2 Diabetes: From Cellular Targets to Cardiovascular Benefit

“…When administered at maximal doses, they are expected to cause an average hemoglobin A1c (HbA 1C ) reduction of 1-1.5%, as a monotherapy schedule [75]. Both drugs can be more effective than either sulfonylurias or metformin in maintaining glycemic control over time [76,77]. The combination of PIO to the classical metformin-sulfonylurea combination also resulted in sustained improvements in glycaemic control and reduced progression to insulin therapy [78].…”