A synthetic semaglutide formulation delivered glycemic control and weight reduction comparable to reference semaglutide among Indian adults with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin, with similar outcomes observed across postprandial blood glucose (PPBG) subgroups. The findings were reported in the AACE Annual Meeting 2026 from a phase III multicenter, randomized, open-label study.

The 24-week trial enrolled 314 adults aged 18-65 years with glycated hemoglobin (HbA1c) levels between 7.0% and 10.5% despite stable metformin therapy of at least 1500 mg daily or the maximum tolerated dose for at least 12 weeks. Participants were randomized in a 1:1 ratio to receive either the synthetic semaglutide injection manufactured by Sun Pharma or the reference semaglutide product as once-weekly subcutaneous injections, with dose escalation from 0.25 mg to 2 mg during the study period.

The primary endpoint was the change in HbA1c at week 24, while secondary endpoints included fasting blood glucose (FBG), PPBG, body weight, and achievement of HbA1c <7.0%. The subgroup analysis included 288 evaluable participants stratified by baseline PPBG levels: <240 mg/dL (subgroup 1 [S1]; synthetic semaglutide n=64, reference semaglutide n=75) and ≥240 mg/dL (subgroup 2 [S2]; synthetic semaglutide n=78, reference semaglutide n=71).

In S1, mean HbA1c reduction from baseline to week 24 was −1.98±0.80% with synthetic semaglutide compared with −1.78±0.90% with the reference product (P=.2001). In S2, reductions were −2.11±0.85% and −2.14±0.88%, respectively (P=.8576). Mean body weight reductions were also similar between treatment groups, ranging from −6.08 kg to −6.25 kg across the two PPBG categories.

Achievement of HbA1c <7.0% at week 24 was comparable between study groups, occurring in 89.0% versus 86.7% of participants in S1 and 59.4% versus 60.6% in S2 in the synthetic and reference semaglutide groups, respectively. Reductions in FBG and PPBG were also comparable across treatment arms.

Gastrointestinal adverse events, including diarrhea, nausea, and vomiting, were the most frequently reported treatment-emergent adverse events. Three level 1 hypoglycemia events were reported overall, including two in the synthetic semaglutide arm and one in the reference arm. No participants required rescue medication during the study, and both treatments were well tolerated.

The findings showed comparable glycemic control, body weight reduction, and tolerability between the synthetic semaglutide formulation and the reference product among Indian adults with T2DM inadequately controlled on metformin, irrespective of baseline PPBG subgroup.