Research Profile
Semaglutide is a GLP-1 receptor agonist developed by Novo Nordisk with a plasma half-life of ~160 hours, enabling once-weekly subcutaneous dosing. It is structurally modified with a C18 fatty acid chain for albumin binding and substitutions at positions 8 and 34 conferring DPP-4 resistance.
GLP-1 is an incretin hormone that augments glucose-dependent insulin secretion, inhibits glucagon, slows gastric emptying, and acts centrally on the hypothalamus to suppress appetite. Semaglutide mimics these actions with greater potency and duration than endogenous GLP-1.
In STEP-1, semaglutide 2.4 mg produced mean body weight reduction of 14.9% vs 2.4% placebo over 68 weeks. Approved as Ozempic (diabetes) and Wegovy (obesity management).
Obesity & metabolic syndrome — STEP 1–5 programme documented consistent weight reduction across diverse populations including type 2 diabetes, prediabetes, and cardiovascular comorbidities.
Type 2 diabetes — SUSTAIN and PIONEER trials demonstrated HbA1c reductions of 1.5–2.0 percentage points. First-line injectable in multiple international guidelines.
Cardiovascular outcomes — SELECT trial (2023) showed 20% reduction in MACE in patients with established CVD and obesity without diabetes.
MAFLD/MASLD — phase 2 NASH trials demonstrate hepatic fat and inflammation reductions. Phase 3 ongoing.
Neurodegeneration — GLP-1Rs expressed throughout CNS. EVOKE programme investigating Alzheimer's prevention. Preclinical data suggest reduced neuroinflammation and amyloid burden.
Addiction research — emerging data on reduced alcohol and substance use via dopaminergic reward pathway modulation.
Primary limiting factor is GI tolerance. Slow titration markedly reduces dropout. Do not combine with tirzepatide — additive GI risk without evidence base.