MD Conference Express ADA 2011 - (Page 18)

ADVERTORIAL Selected Session Highlights Intensification of Insulin Therapy Intensifying Insulin Regimens as β-cell Function Declines Physicians in many countries use combinations of antihyperglycemic agents to achieve the best glycemic control possible under the conditions faced by individual patients with type 2 diabetes.1 As β-cell function declines, most of those treated with oral agents either alone or in combination require insulin therapy.2 How to advance from unsuccessful oral therapy to intensified insulin treatment, however, is a matter of debate. Matthew Riddle, MD, Oregon Health & Science University, Portland, Oregon, USA, presented results from a study on three intensified insulin regimens added to oral therapy. In a 60-week randomized, open-label clinical trial, Dr. Riddle and colleagues compared efficacy, hypoglycemia, and body weight after adding twice a day treatment with premixed 70/30 protamine-aspart/aspart (PREMIX; n=192); glargine+ 0 or 1 prandial glulisine dose (GLARG+0-1; n=189); or glargine plus stepwise glulisine (GLARG+0-3; n=191). Mean baseline HbA1C was 9.4 after a 4-week run-in period on 2 to 3 oral agents. Subjects were an average of 54 years of age, with mean diabetes duration of 9 years, and a body mass index of 33.2 kg/m2. Insulin was titrated to achieve fasting and preprandial glucose <100 mg/dL with HbA1C <6.5%. Each regimen reduced HbA1C (Figure 1), but more subjects had Week 60 HbA1C <7% with GLARG+0-1 (49%; p<0.025) or GLARG+0-3 (45%; p<0.05) than with PREMIX (39%). GLARG+0-1 (24%; p<0.05) or GLARG+0-3 (24%; p<0.01) patients also had less hypoglycemia than patients receiving PREMIX (14%). Mean change in HbA1C at the endpoint (last observation carried forward [LOCF]) was -1.8±0.1% with PREMIX versus -2.1±0.1% (p=0.06) and -2.2±0.1% (p<0.01) with GLARG+0-1 and GLARG+0-3, respectively. Change in body weight at Week 60 was similar among the three regimens. A significantly greater proportion of patients achieved the target HbA1C <7% using glargine-based approaches without confirmed hypoglycemia than did those using premixed insulin. Notably, the GLAR+0-3 regimen, which permitted full basal-bolus insulin therapy, did not appear more effective than GLAR+0-1, in which no more than a single prandial insulin injection was used. Other researchers have taken different approaches to the same challenge of how best to intensify treatment. Owens et al.3 performed a proof-of-concept study on the efficacy of initiating and titrating a single bolus dose of insulin glulisine to baseline insulin glargine plus oral hypoglycemic agents. Data showed that in patients with inadequately controlled type 2 diabetes who are on basal insulin plus oral antidiabetic agents, adding a single injection of insulin glulisine prior to the main meal significantly improved glucose control without undesirable side effects. Figure 1. Mean Change in HbA1C Over Time. 9.6 9.2 8.8 PreMx-2=9.3% GLARG+0-1=9.4% GLARG+0+3=9.4% HbA1C (%) 8.4 8.0 7.6 7.2 6.8 BL 12 24 36 Weeks of Treatment 48 60 7.5% 7.3% 7.2% 7.2% 7.2% 7.1% LOCF LOCF=last observation carried forward; mITT population. Reproduced with permission from M. Riddle, MD. Meneghini et al.4 conducted a 48-week randomized, controlled trial comparing the safety and efficacy of two intensification strategies for the stepwise addition of prandial insulin aspart in patients with type 2 diabetes whose disease was inadequately controlled with insulin detemir. Patients were randomized to either titration based on pre-meal glucose values (SimpleSTEP) or post-meal values (ExtraSTEP). The data indicated that both strategies were equally effective at intensifying therapy in patients with type 2 diabetes who were not achieving glycemic control on basal insulin and oral antidiabetic agents. Deciding When to Stop Titrating Basal Insulin and Start Adding Prandial Insulin Stepwise intensification of insulin treatment to match the progressive decline of endogenous insulin secretion is an effective management strategy in type 2 diabetes.3 However, it is often unclear when titration of basal insulin is maximized and prandial insulin should be added to the therapy. Ariel Zisman, MD, The Endocrine Center of Aventura, Aventura, Florida, USA, presented results of a study on the BeAM factor: an easy-to-determine and objective clinical indicator for making this treatment decision.5 Ideally, basal insulin therapy should match hepatic glucose production and maintain a narrow blood glucose range, including overnight. Large differences between Bedtime and AM (“BeAM” factor) values during treatment suggest that the therapy may have reached maximal titration, and that prandial insulin should be introduced to correct for post-prandial glucose excursions and help achieve the target HbA1C. This peer-reviewed article was based on oral and poster presentations at the ADA 2011 Scientific Sessions. Development of this article was supported by Sanofi. 

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MD Conference Express ADA 2011

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