Current Drug Therapy

Insulin treatment for type 2 diabetes: When to start, which to use

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ABSTRACTIn 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. Further, some experts recommend electively starting insulin therapy in early diabetes. This review addresses practical 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 acceptance 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 hyperglycemia 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 number 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 remain as to when insulin therapy should be started, and which regimen is the most appropriate.

Guidelines from professional societies differ on these points,2,3 as do individual clinicians. 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 insulin treatment, the available preparations, the pros and cons of each regimen, and how the properties of each type of insulin influence attempts to intensify the regimen.

Coexisting physiologic and medical conditions such as pregnancy and chronic renal failure and drugs such as glucocorticoids may alter insulin requirements. I will not cover these special situations, as they deserve separate, detailed discussions.


Early on, patients can be adequately managed with lifestyle modifications and oral hypoglycemic agents or injections of a GLP1 analogue, 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 metformin (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 stratified by hemoglobin A1c level, in which insulin 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 to safety. The AACE/ACE statement gives more weight to the risk of hypoglycemia with insulin treatment, whereas the ADA gives more weight to the risk of edema and congestive heart failure with thiazolidinedione drugs (although both insulin and thiazolidinediones cause weight gain) and to adequate validation of treatments in clinical trials.

Ongoing clinical trials may add insight to this issue. For example, the Outcome Reduction With Initial Glargine Intervention (ORIGIN) study is investigating the effects of the long-acting insulin glargine (Lantus) in early diabetes with regard to glycemic control, safety, 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, individualized treatment should be considered, as we will see below.


The decision to start insulin therapy should be made individually, based on several factors:

  • Whether the patient is willing to try it
  • The degree of hyperglycemia
  • How relevant the potential side effects of insulin are to the patient compared with those of other hypoglycemic agents
  • Whether oral hypoglycemic agents with or without GLP1 analogues are expected to provide the desired benefit
  • The patient’s work schedule and lifestyle factors
  • Cost
  • The availability of nurses, diabetes educators, and others to implement and follow the insulin treatment.

Will patients accept insulin?

Factors that affect whether patients comply with a treatment include the number of pills or injections they must take per day, how often they must check their blood glucose, adverse effects, lifestyle limitations caused by the treatment (especially insulin), and cost. Most patients feel better when their glucose levels are under good control, which is a major motivation for initiating and adhering to insulin. The anticipated reduction of diabetic complications further enhances compliance.

Education promotes compliance. Patients need to know that type 2 diabetes tends to progress and that in time their treatment will have to be intensified, with higher doses of their current drugs and new drugs added or substituted, possibly including insulin. This information is best given early, ie, when the diagnosis is made, even if hyperglycemia is mild at that time.

With newer insulin preparations and delivery devices available, more patients are finding insulin treatment acceptable.


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