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Synthetic Semaglutide Matches Innovator Wegovy for Weight Loss in Indian Adults
A phase III randomised trial in Indian adults with obesity found that a synthetic semaglutide formulation produced nearly identical weight loss to innovator semaglutide (Wegovy®) over 24 weeks, with a least square-mean difference of just 0.15% (95% CI −0.93 to 1.24), formally satisfying the predefined non-inferiority threshold. Both arms achieved substantial mean weight reductions of approximately 14.4–14.6%, suggesting the synthetic formulation is a clinically comparable alternative to the reference product.
What Was Studied
The trial investigated whether a synthetic version of semaglutide manufactured by Alkem Laboratories Limited could produce weight loss outcomes equivalent to those of the innovator once-weekly subcutaneous formulation (Wegovy®, Novo Nordisk) in adults with obesity. The primary outcome was the percentage change in total body weight at 24 weeks, evaluated under a non-inferiority framework — a design well-suited for assessing whether a new formulation can stand in as an effective substitute for an established therapy.
How It Was Studied
This was a phase III, multicentre, randomised, active-controlled non-inferiority trial conducted across 19 sites in India. A total of 249 adults with obesity were enrolled and allocated in a 2:1 ratio to receive either the synthetic semaglutide (test arm, n=166) or innovator semaglutide (reference arm, n=83), both administered as once-weekly subcutaneous injections over 24 weeks. Completion was exceptionally high, with 246 of 249 participants (98.8%) completing the full study period. Non-inferiority was pre-specified as demonstrated if the lower bound of the one-sided 97.5% confidence interval for the between-group difference in weight change did not exceed 4.5 percentage points.
What Was Observed
- Primary endpoint met: Mean percentage weight loss at 24 weeks was −14.39 ± 4.17% in the synthetic semaglutide arm and −14.61 ± 4.36% in the innovator arm — a difference so small as to be clinically negligible. The least square-mean difference was 0.15% (95% CI −0.93 to 1.24), which fell well within the non-inferiority margin, confirming comparable efficacy.
- Clinically meaningful weight loss thresholds: The proportions of participants achieving weight loss greater than 10% were nearly identical — 86.67% in the test arm versus 83.95% in the reference arm, with no statistically significant difference (p = 0.5666). Similarly, weight loss exceeding 15% was achieved by 38.79% and 40.74% of participants respectively, again with no meaningful difference between groups (p = 0.7683).
- BMI reduction: Mean body mass index declined by −4.93 ± 1.43 kg/m² in the synthetic arm and −5.00 ± 1.50 kg/m² in the reference arm, a difference that was not statistically significant (p = 0.7128), reinforcing the comparable magnitude of anthropometric improvement in both groups.
- Safety and tolerability: Treatment-emergent adverse events occurred at nearly equal rates — 55.42% in the test arm and 54.22% in the reference arm — indicating a similar tolerability profile for the synthetic formulation relative to the innovator product.
Why This Matters
Access to GLP-1 receptor agonist therapies such as semaglutide remains limited in lower-middle-income countries largely due to cost and supply constraints. Demonstrating that a domestically manufactured synthetic formulation achieves equivalent efficacy and safety could meaningfully expand therapeutic options for the large and growing population of adults with obesity in India and similar settings. This trial provides the type of head-to-head regulatory-grade evidence needed to support approval and wider adoption of biosimilar or synthetic alternatives in public health frameworks.
How to Read This Result
This well-conducted trial with high completion rates and a clear non-inferiority design supports confidence in the finding, but the 24-week follow-up period leaves open questions about long-term weight maintenance, durability of effect, and delayed adverse events that would require further study before broad clinical conclusions can be drawn.
Limitations
The abstract does not explicitly report study limitations.