Trial results for a Phase 2 study (NCT04969939) investigating semaglutide in combination with NNC0165-1875 for people with obesity were posted on ClinicalTrials.gov on 2026-01-08. The study showed that participants receiving semaglutide 2.4 mg and NNC0165-1875 1.0 mg achieved a mean body weight reduction of -5.55%, compared to -3.06% for those on semaglutide 2.4 mg and placebo.
Background
The study, titled 'A Research Study to Investigate How Well NNC0165-1875 in Combination With Semaglutide Works in People With Obesity,' aimed to evaluate the efficacy of the investigational compound NNC0165-1875 when administered alongside semaglutide for weight management in individuals with obesity.
Trial design
The study (NCT04969939) was a Phase 2 trial that enrolled 120 participants diagnosed with obesity. Participants received weekly injections of either semaglutide 2.4 mg in combination with NNC0165-1875 1.0 mg, semaglutide 2.4 mg with NNC0165-1875 2.0 mg, or semaglutide 2.4 mg with a placebo (either 1.0 mg or 2.0 mg equivalent). The study duration was approximately 26 weeks.
Key results
The trial results showed differences in body weight reduction and adverse events between the combination therapies and semaglutide with placebo.
- For "Percentage Change in Body Weight," participants receiving NNC0165-1875 1.0 mg + Semaglutide 2.4 mg achieved a mean reduction of -5.55% (Standard Deviation: 3.97). In comparison, the Placebo + Semaglutide 2.4 mg group showed a mean reduction of -3.06% (Standard Deviation: 5.46).
- For "Change in Body Weight (kg)," the NNC0165-1875 1.0 mg + Semaglutide 2.4 mg group had a mean change of -4.54 kg (Standard Deviation: 3.22), while the Placebo + Semaglutide 2.4 mg group had a mean change of -2.23 kg (Standard Deviation: 5.16).
An ANCOVA analysis for treatment difference in percentage points showed a value of -2.15 (95.0% CI: -4.24 to -0.06) with a p-value of 0.0437, comparing Week 48 responses with baseline body weight as a covariate.
Regarding safety, the number of "Treatment-emergent Adverse Events (TEAEs)" was 56 Events for NNC0165-1875 1.0 mg + Semaglutide 2.4 mg, 71 Events for NNC0165-1875 2.0 mg + Semaglutide 2.4 mg, and 37 Events for Placebo + Semaglutide 2.4 mg.
Other measured outcomes included changes in Glycosylated Haemoglobin (HbA1c), Fasting Plasma Glucose (FPG), and Fasting Insulin. For HbA1c, both NNC0165-1875 1.0 mg + Semaglutide 2.4 mg and Placebo + Semaglutide 2.4 mg groups showed a mean change of -0.17 percentage point of HbA1c. Changes in FPG and Fasting Insulin were also reported for the NNC0165-1875 1.0 mg + Semaglutide 2.4 mg group as 0.08 mmol/l (Standard Deviation: 0.36) and -14.10 pmol/l (Standard Deviation: 39.31) respectively.
What this means
The results of this Phase 2 study suggest that the combination of semaglutide with NNC0165-1875 may lead to a greater reduction in body weight compared to semaglutide alone in individuals with obesity. The statistically significant treatment difference of -2.15 percentage points in body weight reduction indicates a potential additive benefit. However, the observed increase in treatment-emergent adverse events in the combination arms warrants further investigation into the safety profile of NNC0165-1875.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04969939, titled 'A Research Study to Investigate How Well NNC0165-1875 in Combination With Semaglutide Works in People With Obesity,' were posted on 2026-01-08 on clinicaltrials.gov.