Semaglutide

Semaglutide is a long-acting GLP-1 receptor agonist approved by the FDA in 2017 for type 2 diabetes and 2021 for chronic weight management. It is a synthetic analog of human GLP-1 with amino acid substitutions at positions 8 and 34 and a C-18 fatty diacid side chain attached to lysine 26, extending half-life to approximately 7 days. The STEP and SUSTAIN clinical trial programs demonstrated significant HbA1c reduction and weight loss. The SELECT trial showed cardiovascular benefits in patients with established cardiovascular disease.

PubMed results: 4,338 · Human studies: 2,516 · Animal studies: 2,721

Ranges reflect protocols studied in published research and animal-model extrapolation. Presented for research purposes only, not a recommendation or instruction for human use.

FDA-approved dosing ranges from clinical trials. Gradual titration was used in trials to minimize GI side effects.

• Subcutaneous Injection — standard range 1-2.4 mg weekly, Once weekly. Ongoing treatment
• Oral — standard range 7-14 mg daily, Once daily. Clinical trials investigated oral formulations at 7-14 mg daily ranges administered on an empty stomach

~7 days (SC), ~1 week (high confidence)

Long half-life enables weekly dosing. Absorption from injection site is rate-limiting.

• HbA1c reduction (Strong human clinical data): In SUSTAIN trials, semaglutide reduced HbA1c by 1.5-1.8% vs placebo
• Weight loss (Strong human clinical data): STEP trials showed 15-17% body weight reduction at 2.4 mg weekly dose
• Cardiovascular risk reduction (Strong human clinical data): SELECT trial demonstrated 20% reduction in MACE in patients with CVD

• Nausea — Mild-Moderate, Common (15-20%). Usually transient, resolves with continued use
• Diarrhea — Mild, Common (10-15%)
• Gallbladder disease — Moderate, Uncommon (1-2%)

• Personal or family history of medullary thyroid carcinoma (FDA Boxed Warning): GLP-1 agonists caused thyroid C-cell tumors in rodent studies
• Multiple Endocrine Neoplasia syndrome type 2 (FDA Boxed Warning): Same concern regarding thyroid C-cell tumors

• NCT06715514 — Menopausal Hormone Therapy, GLP-1 Agonists, and Glucose and Energy Homeostasis in Postmenopausal Women With Diabetes (NA), status: RECRUITING. Indications: Menopause, Type 2 Diabetes
• NCT05537233 — ADJUnct Semaglutide Treatment in Type 1 Diabetes (PHASE2), status: COMPLETED. Indications: Type 1 Diabetes, Obesity
• NCT07314684 — GLP1-RAs Effects on Inflammatory and Endothelial Biomarkers in T2DM (PHASE4), status: RECRUITING. Indications: T2DM (Type 2 Diabetes Mellitus)
• NCT06659744 — Emulation of the SUSTAIN6 Diabetes Trial Using Healthcare Claims, status: COMPLETED. Indications: Diabetes Mellitus, Type 2
• NCT05443334 — A Research Study Looking at How Oral Semaglutide Works in People With Type 2 Diabetes in Spain, as Part of Local Clinical Practice, status: COMPLETED. Indications: Diabetes Mellitus, Type 2
• NCT06541509 — Mechanisms of Semaglutide Therapy in Heart Failure Patients (PHASE1 / PHASE2), status: RECRUITING. Indications: Heart Failure, Obesity
• NCT05646199 — Semaglutide vs Metformin in Polycystic Ovary Syndrome (PCOS) (PHASE2 / PHASE3), status: NOT_YET_RECRUITING. Indications: Polycystic Ovary Syndrome
• NCT06243536 — The Effect of Semaglutide on Disordered Eating Behaviour in Type 2 Diabetic Patients (PHASE4), status: UNKNOWN. Indications: Type 2 Diabetes, Overweight, Disordered Eating Behaviors
• NCT07220629 — Study to Explore the Safety and Efficacy of NT-0796 as an Adjunct to Semaglutide in Participants With Obesity (RESOLVE-2) (PHASE2), status: ACTIVE_NOT_RECRUITING. Indications: Obesity
• NCT05597202 — Does the Hematopoietic Stem Cell Govern Residual Inflammatory Cardiovascular Risk in Type 2 Diabetes (PHASE4), status: UNKNOWN. Indications: Type 2 Diabetes
• NCT06475586 — Effect of Semaglutide on the Psoriatic Lesions in Patients With Type 2 Diabetes Mellitus (PHASE4), status: COMPLETED. Indications: Psoriasis Vulgaris, Diabetes Type 2
• NCT03611322 — A Trial to Compare Blood Concentration Levels of Semaglutide Following Subcutaneous Injections of Semaglutide 1 mg by 2 Different Devices (the DV3372 Device and by the PDS290 Semaglutide Pen-injector) (PHASE1), status: COMPLETED. Indications: Diabetes Mellitus, Type 2
• NCT06222437 — Semaglutide and Polycystic Ovarian Syndrome: an Emerging Treatment Strategy (PHASE1), status: WITHDRAWN. Indications: Polycystic Ovary Syndrome
• NCT05813912 — A Research Study to See How a New Weekly Insulin, Insulin Icodec When Given Along With Semaglutide Helps in Reducing the Blood Sugar Level in Patients With Type 2 Diabetes (PHASE3), status: COMPLETED. Indications: Diabetes Mellitus, Type 2
• NCT07323134 — The Effect of Semaglutide on the Intestinal Flora in Obesity, status: NOT_YET_RECRUITING. Indications: Obesity
• NCT03987074 — Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH) (PHASE2), status: COMPLETED. Indications: Nonalcoholic Steatohepatitis
• NCT05501483 — Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes (NA), status: RECRUITING. Indications: Type 2 Diabetes
• NCT06323161 — A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in People With Type 2 Diabetes Treated With Once-daily Basal Insulin With or Without Metformin (PHASE3), status: COMPLETED. Indications: Type 2 Diabetes
• NCT05046873 — A Research Study Looking Into Blood Levels of Semaglutide and NNC0480-0389 When Given in the Same Injection or in Two Separate Injections in Healthy People (PHASE1), status: COMPLETED. Indications: Diabetes Mellitus, Type 2
• NCT05586802 — Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome (PHASE3), status: RECRUITING. Indications: Klinefelter Syndrome