ADO09 Pramlintide-insulin co-formulation improves time in range for type 1 diabetes

Previously Published on– ADO09, a co-formulation of pramlintide and insulin A21G, was associated with better glucose levels, improved time in range and more weight loss among people with type 1 diabetes compared with insulin aspart, according to a presenter.

ADO09 is a new and innovative co-formulation of two hormones missing in type 1 diabetes: insulin and its little sister amylin, co-secreted by the pancreas with insulin,” Gregory Meiffren, PhD, director of clinical development, PKPD and biology at Adocia, told Healio. “When we compared the effect of ADO09 to that of insulin aspart, one of the gold standard prandial insulins, ADO09 improved postprandial blood glucose control, reduced insulin doses and lowered body weight in subjects with type 1 diabeteswho use large insulin doses every day. Meiffren presented findings from the second part of a two-part clinical trial at the American Diabetes Association Scientific Sessions.

In a randomized, double-blind clinical trial, 16 participants with type 1 diabetes (93.8% men; mean age, 46.5 years) were randomly assigned to ADO09 or insulin aspart for 24 days. After a washout period of 5 to 7 days, participants switched to the opposite therapy for 24 days. Follow-up visits were conducted 7 to 15 days after final dosing.

ADO09 improves glucose, CGM metrics

After 24 days, ADO09 reduced incremental area under the curve glucose between 0 and 4 hours on a mixed-meal glucose tolerance test by 69% (P = .0266) and delta 1-hour plasma glucose by 82 mg/dL (P < .0001) compared with insulin aspart. The speed of gastric emptying, as measured by acetaminophen absorption, was 50% lower with ADO09 compared with insulin aspart.

Participants taking ADO09 had 58 minutes more time in range between 70 mg/dL and 170 mg/dL (P = .0432) and 63 minutes more time in range between 80 mg/dL and 140 mg/dL (P = .0107) compared with insulin aspart. ADO09 lowered the time above 180 mg/dL by 80 minutes (P = .0049) and decreased mean 24-hour blood glucose by 7 mg/dL (P = .0127) compared with insulin aspart.

Those taking ADO09 required 12 fewer units of prandial insulin per day compared with insulin aspart (P = .0004). ADO09 was also associated with a mean 1.6 kg reduction in body weight over 24 days, whereas participants taking insulin aspart gained a mean 0.4 kg of body weight.

“Our results demonstrate that the fixed combination of the two hormones blunts the postprandial blood glucose excursions, which remains the most difficult period of the day to control in type 1 diabetes,” Meiffren said. “Additionally, achieving blood glucose targets generally requires intensive insulin therapy, which, however, results in body weight gain. Knowing the obesity epidemic now also hits type 1 diabetes subjects, it is an interesting perspective to develop a postprandial co-formulation which reduces body weight.”

No severe hypoglycemia observed

No serious adverse effects were reported with ADO09 during the trial. Those taking ADO09 reported more gastrointestinal-related events and decreased appetite. Meiffren noted these are consistent with pramlintide’s (Symlin, AstraZeneca) known effects.

No severe hypoglycemic events were observed during the study. There were slightly more hypoglycemic episodes with ADO09 compared with insulin aspart.

Meiffren said a phase 2 clinical trial is now being conducted in Germany with the company Profil to compare ADO09 with insulin lispro (Humalog, Eli Lilly) in a parallel, open-label trial with 80 participants with type 1 diabetes.

“Important endpoints will be the glycemic control assessed by HbA1c change from baseline and continuous glucose monitoring, as well as the body weight change, as we will enroll subjects with a body mass index above 25 kg/m²,” Meiffren said. “This study should allow us to design the phase 3 study in subjects with type 1 diabetes using multiple daily injection treatment. We are also working on developing ADO09 in subjects with type 2 diabetes. This population may indeed benefit from the co-formulation of insulin and amylin since it generally has weight problems.”

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