Is there evidence to support use of premixed or prandial insulin regimens in insulin-naive or previously insulin-treated type 2 diabetic patients?

Regarding the question of how to use insulin in type 2 diabetes, a systematic review conforming to methods of the Cochrane collaboration was published in 2006 (1). This review included studies published in Medline until May 2004. The analysis compared insulin monotherapy with combination therapy with insulin and oral hypoglycemic agent (OHA) in previously insulin-naive patients. With use of the methods detailed in the review (1), 13 randomized controlled trials (RCTs) could be identified and included 1,811 participants with a mean age of 60 years and duration of diabetes of 10 years. The authors concluded that bedtime NPH insulin combined with oral antihyperglycemic agents provides glycemic control comparable with that provided by insulin monotherapy with twice daily insulin or basal/bolus insulin regimens but is associated with less weight gain if metformin is used. However, since May 2004 there has been an exponential increase in the number of patients participating in RCTs comparing basal insulin plus OHA with other insulin regiments with similar OHA (vide infra). Such studies have become possible thanks to the development of rapid- and long-acting insulin analogs and commercial support for studies addressing insulin therapy. This review focuses on comparison of different insulin treatment regimens in both insulin-naive (first objective) and previously insulin-treated (second objective) patients with type 2 diabetes. We wished to examine whether there is an advantage (glycemic control, weight gain, or hypoglycemia) of using premixed and basal-bolus regimens with or without OHA compared with basal insulin and OHA. For the first objective, we used the principles outlined in the previous Cochrane review (1) to compare glycemic control between basal insulin/OHA and other regimens. The latter included regimens with premixed insulin twice daily with or without OHA or regimens using prandial insulin three times daily or multiple insulin injection therapy (basal and prandial three times …