Abstract
The progressive nature of type 2 diabetes (T2D) often results in the need for initiation and subsequent intensification of insulin treatment to achieve glycemic control. The aim of this review is to examine published clinical evidence that has directly compared two recommended treatment approaches in patients with T2D: (1) a ‘basal plus’ regimen, whereby 1–2 injections of prandial insulin are added to basal insulin; or (2) the use of once- or twice-daily premix insulin analogs, which contain both basal and prandial insulin in a single injection. Broadly, the available evidence suggests that both basal plus and premix regimens are comparable in terms of efficacy and safety when used for insulin initiation in insulin-naïve patients and intensification in patients who have failed on basal insulin; instances of greater glycemic control are observed with premix insulin; however, these are often accompanied by increases in hypoglycemia and/or weight relative to basal plus treatment, and results should be interpreted within the context of total insulin doses used. Relatively low numbers of patients achieved glycemic control when both regimens were used for insulin intensification following failure of basal insulin, suggesting that a full basal–bolus regimen and/or the use of different treatments is clinically indicated in certain patients. In summary, the current review argues that both basal plus and premix insulin regimens are relatively efficacious and safe options for patients with T2D during both insulin initiation in insulin-naïve patients and intensification in patients who have failed on basal insulin. This emphasizes the important role of patient-centered factors in clinical decision-making. Funding: Novo Nordisk.
Highlights
Type 2 diabetes (T2D) is a chronic disease that results in a majority of patients requiring insulin treatment due to the progressive decline in pancreatic b-cell function [1].Clinical guidelines in many countries, including those of the Australian DiabetesSociety (ADS) and International DiabetesFederation (IDF), suggest that insulin can be initiated with either a long-acting basal insulin administered once daily (OD), or premix insulin administered OD or twice daily (BID), when lifestyle changes and treatment with glycemic-lowering, oral antidiabetic drugs (OADs) are no longer sufficient to help the patient achieve recommended glycemic targets [2, 3].In clinical practice, insulin switching and/or intensification following initiation with basal insulin is commonly required
For the trials assessing insulin initiation, both premix (OD or BID) and basal plus treatment resulted in a reduction in HbA1c from baseline, in patients who had failed on lifestyle modification and OAD treatment [9, 28]
The current review indicates that the similarities between basal plus and premix (OD and BID) regimens when either initiating or intensifying insulin treatment could be argued to be generally greater than the differences, and superiority in one area may be at the cost of increased adverse events (AEs)
Summary
Type 2 diabetes (T2D) is a chronic disease that results in a majority of patients requiring insulin treatment due to the progressive decline in pancreatic b-cell function [1].Clinical guidelines in many countries, including those of the Australian DiabetesSociety (ADS) and International DiabetesFederation (IDF), suggest that insulin can be initiated with either a long-acting basal insulin (e.g., insulin glargine, insulin detemir, insulin degludec) administered once daily (OD), or premix insulin administered OD or twice daily (BID), when lifestyle changes and treatment with glycemic-lowering, oral antidiabetic drugs (OADs) (usually in combination therapy) are no longer sufficient to help the patient achieve recommended glycemic targets [2, 3].In clinical practice, insulin switching and/or intensification following initiation with basal insulin is commonly required. Federation (IDF), suggest that insulin can be initiated with either a long-acting basal insulin (e.g., insulin glargine, insulin detemir, insulin degludec) administered once daily (OD), or premix insulin administered OD or twice daily (BID), when lifestyle changes and treatment with glycemic-lowering, oral antidiabetic drugs (OADs) (usually in combination therapy) are no longer sufficient to help the patient achieve recommended glycemic targets [2, 3]. Switching and/or intensification is often required to reduce postprandial plasma glucose (PPG) excursions; basal-only regimens are unlikely to cover these instances of postprandial hyperglycemia, and closer attention to PPG is usually necessary to achieve tight glycemic targets [5]. For insulin-treated patients with T2D who require intensification, clinical guidelines recommend to: (1) continue with basal insulin OD and add rapid-acting prandial insulin in a ‘stepwise’ manner, up to three-times daily (TID), i.e., a full basal–bolus regimen; or (2) intensify or transfer to premix insulin BID [2, 3]
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