Comparison of Basal Insulin Added to Oral Agents Versus Twice-Daily Premixed Insulin as Initial Insulin Therapy for Type 2 Diabetes

Abstract

OBJECTIVE -To compare the efficacy and safety of adding once-daily basal insulin versus switching to twice-daily premixed insulin in type 2 diabetic patients insufficiently controlled by oral antidiabetic agents (OADs). RESEARCH DESIGN AND METHODS-In a 24-week, multinational, multicenter, open, parallel group clinical trial, 371 insulin-naïve patients with poor glycemic control (fasting blood glucose [FBG] Ն120 mg/dl, HbA 1c 7.5-10.5%) on OADs (sulfonylurea plus metformin) were randomized to once-daily morning insulin glargine plus glimepiride and metformin (glargine plus OAD) or to 30% regular/70% human NPH insulin (70/30) twice daily without OADs. Insulin dosage was titrated to target FBG Յ100 mg/dl (both insulins) and predinner blood glucose Յ100 mg/dl (70/30 only) using a weekly forced-titration algorithm.RESULTS -Mean HbA 1c decrease from baseline was significantly more pronounced (Ϫ1.64 vs. Ϫ1.31%, P ϭ 0.0003), and more patients reached HbA 1c Յ7.0% without confirmed nocturnal hypoglycemia (45.5 vs. 28.6%, P ϭ 0.0013) with glargine plus OAD than with 70/30. Similarly, FBG decrease was greater with glargine plus OAD (adjusted mean difference Ϫ17 mg/dl [-0.9 mmol/l], P Ͻ 0.0001), and more patients reached target FBG Յ100 mg/dl with glargine plus OAD than with 70/30 (31.6 vs. 15.0%, P ϭ 0.0001). Glargine plus OAD patients had fewer confirmed hypoglycemic episodes than 70/30 patients (mean 4.07 vs. 9.87/patient-year, P Ͻ 0.0001).CONCLUSIONS -Initiating insulin treatment by adding basal insulin glargine once daily to glimepiride plus metformin treatment was safer and more effective than beginning twice-daily injections of 70/30 and discontinuing OADs in type 2 diabetic patients inadequately controlled with OADs. Diabetes Care 28:254 -259, 2005T he association between poor glycemic control and the occurrence of micro-and macrovascular complications has been demonstrated in patients with type 1 and type 2 diabetes (1-3); however, achieving glycemic control, preferably with HbA 1c values Ͻ7%, can markedly reduce the risk of such complications (4) and is now recommended clinical practice (5,6). In many patients, insulin treatment is required to achieve good glycemic control (1).Consensus opinion on how or when to initiate insulin treatment in type 2 diabetic patients is lacking, and treatment regimens are known to vary between countries. Since most patients with type 2 diabetes are older and physicians' time is limited, the insulin regimen should be easy to apply. However, few studies have directly compared the leading methods. We studied two commonly used, simple regimens for initiating insulin therapy. One approach consists of stopping oral antidiabetic agent (OAD) therapy and initiating two injections of insulin, often premixed insulin containing a fixed ratio of regular and intermediateacting insulin (NPH), administered twice daily. The European Diabetes Policy Group (5) recommended that, in the majority of patients with type 2 diabetes, insulin therapy should be initiated using premixed insulin twice daily. N...

Comparison of the pharmacokinetics and pharmacodynamics of biphasic insulin aspart and insulin glargine in people with type 2 diabetes

“…The usual options are to include the use of premixed insulins either with [6] or without [7] oral agents or to use a basal insulin also with [5] or without oral agents, with the further option to add prandial insulin if and when required. Although overall similar reductions in HbA 1c may be achieved by these two options, there may be substantial differences in the number of hypoglycaemic episodes observed between treatment regimens.…”

“…However, there were more frequent hypoglycaemic events in the patients receiving premixed insulin twice daily. In a different study [7], two groups of patients with type 2 diabetes who were failing on oral hypoglycaemic medication were compared. In this 24-week study, one group received a morning injection of insulin glargine in addition to 3-4 mg glimeperide and 850 mg or more of metformin.…”

Glycemic control and adherence to basal insulin therapy in Taiwanese patients with type 2 diabetes mellitus

“…The clinical trials showed that the use of basal insulin as an add‐on to OAD in patients with type 2 diabetes achieved 7% HbA1c, and approximately half of the patients experienced symptomatic hypoglycemia20, 21, 22, 23, 24. However, in real‐world practice, a retrospective USA study and two prospective studies in Ireland and Japan found that approximately just 20% of the patients taking basal insulin could achieve HbA1c <7% with a low rate of hypoglycemia16, 25, 26.…”

Optimal insulin regimens in type 2 diabetes mellitus: systematic review and meta-analyses

“…Whichever is chosen, starting insulin alongside rather than instead of OHAs improves glycaemic control and reduces the required daily insulin dose [11,15,16].…”