A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Acmopatide (CT-868), a Fully Biased GLP-1/GIP Receptor Agonist, in Adults With Type 1 Diabetes and Overweight or Obesity
Klara R. Klein, Jeremy Pettus, Gabriele E. Sonnenberg, Halis K. Akturk, Richard Pratley, Brian Ulmer, Na Li, Jingtao Wu, Manu V. Chakravarthy, , Andrew Ahmann, Timothy Bailey, Anuj Bhargava, Thomas Blevins, Bruce Bode, Shafer Boeder, Frances Broyles, Anna Chang, Lori Gerard, Edward Jauch, Mark Kipnes, Dan Lender, David Liljenquist, Kathryn Lucas, Eduardo Luna, Joel Neutel, Jean Park, Athena Philis-Tsimikas, Joseph Ravid, Heidi Shea, Michelle WelchOBJECTIVE
To evaluate the efficacy and safety of acmopatide, a signal-biased glucagon-like peptide 1/glucose-dependent insulinotropic polypeptide receptor agonist, in adults with type 1 diabetes (T1D) and overweight/obesity.
RESEARCH DESIGN AND METHODS
In this phase 2, 16-week, randomized, double-blind, placebo-controlled, multicenter study, adults with T1D (HbA1c 7.0–10.0%; BMI ≥27 kg/m2) were randomized 1:1:1:1 to once-daily subcutaneous acmopatide (1.8, 4.1, or 6.6 mg) or volume-matched placebo. The primary end point was change from baseline (CFB) in HbA1c (%) at week 16; secondary end points included percent CFB in body weight and insulin dose.
RESULTS
Overall, 111 participants were randomized (placebo n = 29, acmopatide 1.8 mg n = 27, 4.1 mg n = 28, 6.6 mg n = 27). Mean (SD) baseline HbA1c was 7.5% (0.6), and mean BMI was 34.3 (5.6) kg/m2. Acmopatide improved HbA1c (least squares [LS] mean CFB −0.4 to −0.6% vs. −0.3% with placebo; nominally significant placebo-adjusted difference for 4.1 mg: –0.3% [90% CI −0.6 to −0.1]; P = 0.020). HbA1c <7.0% was achieved by 55.6% of participants receiving acmopatide 4.1 mg vs. 33.3% receiving placebo. Acmopatide-treated participants demonstrated reductions in body weight (LS mean CFB −3.3 to −6.7% vs. 0.3% with placebo; all P < 0.01), total daily insulin dose (−3.4 to –14.9% more than placebo for acmopatide 4.1 and 6.6 mg), and mean systolic blood pressure (−3.1 to −8.4 mmHg vs. −3.3 mmHg with placebo). Adverse events were primarily gastrointestinal. No diabetic ketoacidosis (DKA) or severe hypoglycemia events occurred.
CONCLUSIONS
In adults with T1D and overweight/obesity, acmopatide was associated with improved glycemic control and clinically meaningful weight loss without DKA or severe hypoglycemia events.