Type II diabetes - CJC-1131
More than 90% of those with diabetes in the developed world have the Type II form of the disease.
More than 90% of those with diabetes in the developed world have the Type II form of the disease.
It is a growing problem as our lifestyles have become more unhealthy, with risk factors including being overweight, poor diet, age, lack of physical activity and a family history. Unlike Type I, where insulin production fails, it is the result of the body becoming unable to use the insulin it makes, even though it is making sufficient amounts. The World Health Organization is now predicting that by 2025 the best part of 300 million people around the world will have the condition.
Glucagon-like peptide 1 (GLP-1) is one of the hormones that is responsible for the body's insulin secretion and glucose regulation, and increases the secretion of insulin when glucose is ingested orally. It also suppresses glucagon secretion, and delays gastric emptying. Although response to GLP-1 is lowered in patients with Type II diabetes, it cannot be used therapeutically as it is broken down too quickly. US company ConjuChem is developing a synthetic analogue, CJC-1131, in which enzymatic degradation is prevented by covalently bonding GLP-1 to human serum albumin, a technique that raises its half-life to that of the albumin, about 15 days.1
Several clinical studies have been carried out. A total of 22 patients with Type II diabetes were given daily injections of CJC-1131 in doses of 2, 4 or 8 µg/kg for 14 days, or at 20 µg/kg for 20 days in a randomised double blind placebo-controlled trial.2 It was well tolerated, with the only problems being mild nausea and vomiting in some cases. Glycaemia was reduced in a dose-dependent manner, and no hypoglycaemia was observed.
A further open label study was carried out to compare the efficacy and safety of different dosing regimes.3 Patients were given increasing doses of the drug once a day for four weeks and then randomised to doses once a day, two or three times a week or once a week for eight further weeks. In the first 48 patients to complete the trial, the first part of the trial reduced glycosylated haemoglobin levels by an average of 0.6%.
In a multi-centre double blind placebo-controlled phase II trial, 85 patients with poor glycaemic control on metformin or metformin plus a sulphonylurea drug were given either metformin alone or in combination with CJC-1131 once a day for three months in doses of up to 8 µg/kg. When compared with placebo, the addition of high dose CJC-1131 gave better glycaemic control than metformin alone. The most common side-effects were nausea and vomiting, but the incidence was low. Trials are continuing, including using additional diluents to reduce side effects and improve stability.