STEP 2 — Semaglutide 2.4 mg + T2D: 9.6% Weight Loss (Lancet 2021)

STEP 2 (Davies et al., Lancet 2021) was the pivotal randomized controlled trial establishing semaglutide 2.4 mg for chronic weight management in adults with type 2 diabetes — extending the STEP 1 obesity finding into the dual-indication population. Trial design. A 68-week, double-blind, placebo-controlled, phase 3 RCT (NCT03552757). Participants were randomized 1:1:1 to once-weekly subcutaneous semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo, all with lifestyle intervention (reduced-calorie diet and increased physical activity). Conducted across 12 countries, 149 sites. Population. 1,210 adults with type 2 diabetes (HbA1c 7-10%) and overweight or obesity (BMI ≥27 kg/m²). Mean baseline BMI 35.7 kg/m²; mean age 55 years; 51% women. Primary endpoints. Percentage change in body weight at week 68, and the proportion achieving ≥5% weight loss. Key results. Mean body-weight loss was 9.6% on semaglutide 2.4 mg, 7.0% on semaglutide 1.0 mg, and 3.4% on placebo. 68.8% of patients on semaglutide 2.4 mg achieved ≥5% weight loss (vs 57.1% on 1.0 mg vs 28.5% on placebo). HbA1c reductions were comparable across both semaglutide arms (~1.6% reduction) and substantially larger than placebo (-0.4%). Adverse events. Gastrointestinal events (nausea, diarrhea, vomiting, constipation) were the most common, similar to STEP 1, mostly mild-to-moderate and concentrated during dose escalation. Indian context. Type 2 diabetes is highly prevalent in India (~10% of adults), and the Indian phenotype shows higher visceral adiposity and earlier metabolic complications at lower BMIs than Western populations. STEP 2 confirms that semaglutide 2.4 mg delivers both weight loss and glycemic control in patients with both indications — relevant given that several Indian generic brands (Noveltreat, Semaglyn, SUNDAE, Semasize) are now DCGI-approved for both type 2 diabetes and obesity.