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Issue 95 Item 10 Another Treatment Option Glucagon-like Peptide 1 (GLP-1) Lookin

Mar 13, 2002

May turn out to be beneficial for the treatment of type 2 diabetes. A study involving continuous administration of GLP-1 to type 2 diabetics, undertaken by Dr Jens Juul Holst, Department of Medical Physiology, The University of Copenhagen, Copenhagen, Denmark, is showing positive results after 6 weeks of therapy.

Type 2 diabetes affects an estimated 10 percent of adults over 60 years of age and is now being diagnosed in teenagers as well. Treatment normally includes alteration to diet, exercise, oral hypoglycemic agents, and — if needed – insulin.

Clinicians point out that in type 2 diabetes, strict glycemic control reduces the risk of micro-vascular complications, but the deterioration of b-cell function seems inevitable.

Glucagon-like peptide 1 (GLP-1) is an intestinally produced peptide hormone secreted in response to intake of food and has an important role in regulating postprandial blood glucose concentrations. It has been proposed as a treatment for type 2 diabetes.

Dr Holst and colleagues recruited 20 patients with type 2 diabetes and assigned 10 to receive continuous subcutaneous infusion of GLP-1, and 10 to receive saline for six weeks. Assessments including b-cell function, measurement of blood glucose concentration, insulin sensitivity, and ratings of appetite, were recorded at baseline, one and six weeks.

The clinicians found that in the GLP-1 group, fasting and eight-hour average blood glucose decreased by 4.3 mmol/L (77mg/Dl) and 5.5 mmol/L (99mg/Dl) respectively. Bodyweight decreased by 1.9 kg, and appetite was reduced. Both insulin sensitivity and b-cell function improved, and there were no reported side-effects.

Dr Holst notes that the study has some methodological constraints: it was not randomized, nor double blind, "and such observational studies can overestimate intervention effects compared with randomized trials."

On the other hand, patients were similar at entry, which minimizes selection bias; most outcome measures were biochemical analyses, and several were analyzed independently from the investigators; and the patients were masked to the intervention.

The researchers said that the pilot study indicates that a GLP-1 based treatment is likely to be effective in the long-term.

They add that "some sort of failure might have been expected, because treatment is based on an exaggerated supply of one of the natural factors of blood-glucose regulation. The improved insulin sensitivity, b-cell function, body weight and free-fatty-acid levels during treatment could not have been predicted, and probably reflect the profound improvement of metabolic regulation occurring during treatment."

Dr Holst concludes: "Our hope is that this new treatment, in addition to effectively correcting the metabolic disturbances of the disease, may actually help restore the underlying defective b-cell function." Lancet 2002; 359: 824-30