Exenatide or Insulin Glargine for Suboptimally Controlled Diabetes?

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The summary below is from the full report titled "Exenatide versus Insulin Glargine in Patients with Suboptimally Controlled Type 2 Diabetes. A Randomized Trial." It is in the 18 October 2005 issue of Annals of Internal Medicine (volume 143, pages 559-569). The authors are R.J. Heine, L.F. Van Gaal, D. Johns, M.J. Mihm, M.H. Widel, and R.G. Brodows, for the GWAA Study Group.

What is the problem and what is known about it so far?

Patients with type 2 diabetes have impaired ability to store energy from food and high blood sugar levels. Over time, they may experience complications like kidney disease, heart disease, blindness, and nerve damage (neuropathy). To help avoid some of these problems, doctors try to control patients' blood sugar levels with diet and diabetes drugs. Diabetes drugs include glucose-lowering pills, such as metformin and sulfonylurea drugs. Although these pills help, many patients do not achieve or cannot sustain good glucose control with pills alone. Options for these patients are to add drugs that are given as injections, such as insulin glargine (a long-acting insulin) or exenatide (a new incretin mimetic drug). Because exenatide is a new drug, however, we know relatively little about its benefits and harms compared with insulin.

Why did the researchers do this particular study?

To compare the benefits and harms of exenatide and insulin glargine injections in patients with type 2 diabetes who were already taking 2 oral blood glucose–lowering drugs.

Who was studied?

551 adults with type 2 diabetes who had suboptimal glucose control despite taking metformin and a sulfonylurea.

How was the study done?

The researchers recruited patients with type 2 diabetes from 82 sites in 13 countries. All patients were taking maximally effective doses of metformin and a sulfonylurea for at least 3 months and had hemoglobin A_1c levels ranging from 7% to 10%. They were randomly assigned to receive either exenatide injections before morning and evening meals or insulin glargine injections at bedtime. Exenatide doses were 5 µg twice daily for 4 weeks, then 10 µg twice daily. Insulin glargine doses began at 10 units daily and were adjusted in 2-U increments every 3 days as needed to try to reach a fasting blood glucose target of 100 mg/dL. During a 26-week follow-up period, patients were asked regularly about adverse effects, were weighed, and had multiple blood tests to assess glucose control.

What did the researchers find?

Both exenatide and insulin glargine improved overall glucose control. Both reduced hemoglobin A_1c level by about 1% from baseline levels that had averaged about 8.2%. Patients in the exenatide group lost about 5 pounds, and patients in the insulin glargine group gained about 4 pounds. Patients reported more adverse effects with exenatide than with insulin glargine, including nausea (57.1% compared with 8.6%), vomiting (17.4% compared with 3.7%), and diarrhea (8.5% compared with 3.0%).

What were the limitations of the study?

The patients and their doctors knew which drugs the patients were receiving. Of the patients receiving exenatide, 19.4% stopped the injections (withdrew from the study) compared with 9.7% of the patients receiving insulin. Only 21.6% and 8.6% of the patients taking insulin and exenatide, respectively, achieved target fasting glucose levels of 100 mg/dL.

What are the implications of the study?

Both exenatide and insulin glargine can improve glucose control in patients with type 2 diabetes whose disease is not controlled despite taking 2 oral blood glucose–lowering drugs. Exenatide is more likely than insulin glargine to cause gastrointestinal adverse effects.