Induces Weight Loss in Patients with Type 2 Diabetes. The human incretin hormone GLP-1 has several antidiabetic actions which have been demonstrated in patients with type 2 diabetes: Strictly glucose-dependant stimulation of insulin secretion, suppression of glucagon levels, delay of gastric emptying, and weight loss.
Since native GLP-1 is rapidly degraded by the peptidase DPP IV, a sustained release formulation of a DPP IV resistant analogue, LY307161SR, was developed for single daily administration.
In this study, 24 patients with Type 2 diabetes (age: 58+/-1.5 y; weight: 90.9+/-2.1 kg; BMI: 30.2 +/-0.6 kg/m2; HbA1c: 7.3+/-0.1 %; on diet (16), metformin (7), or metformin plus sulfonylurea participated in a single blind dose-escalation study. Patients received LY307161 SR treatment as a single injection prior to breakfast with either 2.5 mg or 3.5 mg for 6 days. In a third group a dose of 4.5 mg was given for 21 days.
Treatment with LY307161 SR was well tolerated.. Once daily administration of LY307161 SR resulted in sustained drug concentrations for the duration of the 24 hour dosing interval. LY307161 plasma concentrations after once daily dosing for 6 days were approximately 3-fold higher than single dose values. Mean average LY307161 concentrations ranged from 370 to 620 pg/mL across the entire dose range.
Fasting glucose was lowered by 19, 24, and 15% and 2 hour post prandial glucose peaks were reduced by 26, 37, and 27% in the 2.5, 3.5, and 4.5 mg dosing groups, respectively, compared to pre-treatment values.
No hypoglycemia was observed. Body weight was lowered at all doses. Six day treatment with 2.5 and 3.5 mg/d resulted in 1.1+/-0.7kg (1.2%) and 1+/-0.7 kg (1%) weight loss respectively. Following 4.5 mg/d for 21 days patients had lost 2.1+/-0.5 kg (2.3%) body weight, indicating a continuous weight reducing effect..
LY307161 SR may offer a unique new treatment for patients with type 2 diabetes that combines the benefits of weight loss with improved glycemic control. American Diabetes Association’s 62nd Annual Scientific Sessions