Amykretin ensures unprecedented weight loss in an early study for the treatment of obesity

In the last study published in LancetA group of researchers assessed safety, tolerance, pharmacokinetics and effects that reduce the weight of subcutaneous amicretin once a week in adults who are overweight or obesity.

Background

Obesity affects more than one billion people around the world. It drives serious conditions, such as cardiovascular diseases, type 2 diabetes and sleep apnea. However, many people still do not meet their health goals, despite imitating slimming drugs glucagon-Peptide similar 1 (GLP-1) or glucose-dependent insulinotropic polypeptide (GIP).

The intestinal hormone amylin, which suppresses appetite and slows down the gastric emptying, increases the effects of GLP-1 therapy when used in combination. Amykretin is a single peptide designed for activation of GLP-1 receptors, amylin and calcitonin at the same time, potentially providing a stronger and longer weight control.

Safety in regular use and effectiveness This multi -level approach in humans remains unclear, emphasizing the need for further research.

About the study

Investigators conducted a five -part, randomized, controlled placebo phase sample 1b/2a in one place in the United States (San Antonio, Texas). The qualifying adults (aged 18-55) had a body mass mass indicator (BMI) of 27.0–39.9 kg/m² and a lack of serious diseases such as diabetes. Participants received passion or placebo as a weekly subcutaneous injection.

Part A tested individual growing doses (0.3 mg, 0.6 mg, 1.0 mg). Part B to E studied many doses in separate cohorts: Part B escalated doses up to 60 mg in 36 weeks; Part C is escalated to the dose of 20 mg over the last 12 weeks 36 weeks; Part D escalated to the maintenance dose of 5 mg over the last 12 weeks 28 weeks; And part E escalated to a maintenance dose of 1.25 mg over the last 12 weeks.

The main end point was the frequency of undesirable adverse events. Secondary endpoints included weight changes, pharmacokinetic indicators (maximum plasma concentration and area under the curve) and exploratory metabolic markers such as fasting glucose on fasting and glycated hemoglobin (HBA1C).

Researchers monitored participants using laboratory tests, electrocardiograms and safety visits, and analyzed the results using statistical models adapted for the starting weight.

Research results

Between September 2023, until April 2024, investigators enrolled 125 adults and randomly assigned 101 to the body of migraine and 24 to placebo at one center in San Antonio, Texas. Participants were 18-55 years old, they had output BMI from 30.0 to 33.1 kg/m² in groups (with an average average of 33.4 kg/m²) and weighed from 83.6 to 99.1 kg at the beginning.

Part A assessed single doses of 0.3 mg, 0.6 mg and 1.0 mg and confirmed acceptable tolerance. Part B to E then evaluated various dosage schemes: Part B escalated weekly doses up to 60 mg within 36 weeks; Part C for a dose of 20 mg; Part D for the maintenance dose of 5 mg; and part E for the conservation dose of 1.25 mg, each with a 12-week maintenance phase at the final dose.

Thirty -eight bodily recipients (37%) and four placebo recipients (17%) have ceased to participate, most often for reasons without security (e.g. withdrawal of consent, taking recreational drugs). Importantly, most of the discontinuities in the Placebo group were not associated with treatment, which confirms the likely nocebo effect.

Adverse events with treatment occurred in 92% of Jajkretin users compared to 100% placebo participants in the BE part report at least one event. The symptoms of the digestive tract dominated and were generally mild or moderate intensity.

Nausea was affected by 82%, vomiting 53%, and diarrhea 41%of treated participants, reaching the peak while floating up and then decreasing. The delight of dissaesthesia changed depending on the dose: 18% in part B (60 mg), 29% in part C (20 mg) and 6% in part D (5 mg), solving in all cases except one. A single case of mild pancreatitis in bile stone occurred with a participant C during the dose escalation (2.5 mg); Later, it went to a serious repetitive event, but decided without consequences until the end of the examination.

The reduction of the mass was fast, dependent on the dose and persisted. At the appropriate time points of the final processing, the estimated average percentage losses on the output value were:

• 24.3% with 60 mg (week 36)
• 22.0% with 20 mg (week 36)
• 16.2% with 5 mg (week 28)
• 9.7% with 1.25 mg (week 20)

Placebo groups showed mass changes -1.1% (part B), +1.9% (part C), +2.3% (part D) and +2.0% (part E). The advantage to Placebo was visible to 4 weeks and extended as part of the study, without observing the weight loss of weight loss during the 12-week maintenance phase in any cohort. Analyzes with a mixed model of repeated measurements, adaptation to the output weight, interruption and missing data, gave virtually identical estimates, strengthening accuracy.

Metabolic markers have shown exploration improvement in parallel with weight. Fasting glucose levels fell by 0.8 mmol/l, and HBA1C levels dropped by 0.6 percentage points in the highest dose group, although statistical significance compared to placebo was inconsistent in doses. Lipid profiles and sitting blood pressure remained neutral.

Continuous electrocardiography did not reveal a clinically significant QT extension and a temporary impulse growth by about 10 beats per minute after the initial injections resolved spontaneously. Antibodies appeared in 29% (5/17) parts B (60 mg), 21%