In type 2 diabetes mellitus, oral hypoglycemic agents and analogues of glucagon-like peptide-1 provide adequate glycemic control early in the disease. Insulin therapy becomes necessary for those with advanced disease. Fur- ther, some experts recommend electively starting insulin therapy in early diabetes. This review addresses practi- cal approaches to insulin therapy, particularly when it is indicated and which regimen to use.
Whether to start insulin therapy and which regimen to use depend on a number of factors, including the patient’s ac- ceptance and willingness to adhere to the therapy.
A common way to start is to add a once-daily dose of a long-acting insulin at bedtime (basal insulin) to the patient’s antidiabetic regimen.
Basal regimens do not control postprandial hyperglyce- mia very well. Another option is to take a long-acting (basal) insulin along with a rapid-acting (prandial or bolus) insulin before meals. Multiple formulations of premixed insulins are available and are convenient to use among new users.
Basal-bolus regimens, which involve injections of rapid- acting insulin before meals and long-acting insulin at bedtime, are gaining popularity. Their cost and the num- ber of injections may affect patient acceptance of this treatment.
Many patients with type 2 diabetes eventually need insulin, as their ability to produce their own insulin from pancreatic beta cells declines progressively.1 The questions re- main as to when insulin therapy should be start- ed, and which regimen is the most appropriate.
Guidelines from professional societies dif- fer on these points,2,3 as do individual clini- cians. Moreover, antidiabetic treatment is an evolving topic. Many new drugs—oral agents as well as injectable analogues of glucagon-like peptide-1 (GLP1) and insulin formulations— have become available in the last 15 years.
In this paper, I advocate an individualized approach and review the indications for insu- lin treatment, the available preparations, the pros and cons of each regimen, and how the properties of each type of insulin influence at- tempts to intensify the regimen.
Coexisting physiologic and medical condi- tions such as pregnancy and chronic renal fail- ure and drugs such as glucocorticoids may alter insulin requirements. I will not cover these special situations, as they deserve separate, de- tailed discussions.
■ WHEN SHOULD INSULIN BE STARTED? TWO VIEWS
Early on, patients can be adequately managed with lifestyle modifications and oral hypogly- cemic agents or injections of a GLP1 ana- logue, either alone or in combination with oral medication. Later, some patients reach a point at which insulin therapy becomes the main treatment, similar to patients with type 1 diabetes.
The American Diabetes Association
(ADA), in a consensus statement,2 has called for using insulin early in the disease if lifestyle management and monotherapy with metfor- min (Glucophage) fail to control glucose or if lifestyle management is not adequate and metformin is contraindicated. The ADA’s goal hemoglobin A1c level is less than 7% for most patients.
The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE), in another consensus statement, use an algorithm strati- fied by hemoglobin A1c level, in which insu- lin is mostly reserved for when combination therapy fails.3 Their goal hemoglobin A1c level is 6.5% or less for most patients.
Comment. Both consensus statements make exceptions for patients presenting with very high blood glucose and hemoglobin A1c levels and those who have contraindications to drugs other than insulin. These patients should start insulin immediately, along with lifestyle management.2,3
Both consensus statements give priority I believe a goal to safety. The AACE/ACE statement gives hemoglobin A1c more weight to the risk of hypoglycemia <7%is
with insulin treatment, whereas the ADA reasonable gives more weight to the risk of edema and
congestive heart failure with thiazolidinedi-
one drugs (although both insulin and thia-
zolidinediones cause weight gain) and to
adequate validation of treatments in clini-
Ongoing clinical trials may add insight to this issue. For example, the Outcome Reduc- tion With Initial Glargine Intervention (OR- IGIN) study is investigating the effects of the long-acting insulin glargine (Lantus) in early diabetes with regard to glycemic control, safe- ty, and cardiovascular outcomes.4 This study is expected to end this year (2011). The safety of alternative treatment options is also under investigation and scrutiny. In the interim, in- dividualized treatment should be considered, as we will see below.