Semaglutide — compound monograph
GLP-1 receptor agonist (acylated, long-acting). Approved. The Institute assesses 11 outcomes for this compound and grades the strongest at high certainty.
§1Identification and status
§1.1Nomenclature
- Preferred name
- Semaglutide
- Compound class
- GLP-1 receptor agonist (acylated, long-acting)
- Assessment series
- Incretin receptor agonists
- Synonyms and codes
- NN9535 · NNC0113-0217 · semaglutide (INN) · Ozempic (trade) · Wegovy (trade) · Rybelsus (trade)
- Route as evaluated
- Subcutaneous once weekly; oral once daily with a permeation enhancer (see separate monograph)
§1.2Chemistry
Chemical identifiers are reproduced where they are public. Where a structure has not been published the monograph records not disclosed rather than constructing one.[1]
- CAS registry number
- 910463-68-2
- Molecular formula
- C187H291N45O59
- Average mass
- 4113.58
- Monoisotopic mass
- 4111.10
- ATC classification
- A10BJ06 · A10BX16 (combination)
§1.3Sequence and structural notes
A 31-residue analogue of human GLP-1(7-37). Alanine at position 8 is replaced by α-aminoisobutyric acid to resist dipeptidyl peptidase-4 cleavage; lysine at position 34 is replaced by arginine to direct acylation; lysine 26 carries a γ-glutamate spacer, two 8-amino-3,6-dioxaoctanoic acid units and an octadecanedioic (C18) diacid that mediates reversible albumin binding.
§1.4Assessment status
The Institute assesses Semaglutide across 11 indications and grades the strongest of them at high certainty. Holds a marketing authorisation for at least one indication in at least one jurisdiction.
Table 1. Assessed outcomes for Semaglutide, ordered by certainty. Each row links to the per-indication evidence extract.
| Indication | Effect as recorded | Certainty | Trials |
|---|---|---|---|
| Atherosclerotic cardiovascular disease and cardiovascular risk reduction | Three-point MACE hazard ratio 0.80 in adults with overweight or obesity and established cardiovascular disease without diabetes | High | 2 |
| Chronic kidney disease in type 2 diabetes | Composite kidney outcome hazard ratio 0.76 in type 2 diabetes with chronic kidney disease | High | 1 |
| Obesity and overweight in adults | −14.9 % body weight at 68 weeks with semaglutide 2.4 mg versus −2.4 % with placebo | High | 5 |
| Type 2 diabetes mellitus | −1.5 to −1.8 % HbA1c at 30–56 weeks versus placebo; superior to dulaglutide 1.5 mg in a head-to-head comparison | High | 4 |
| Heart failure with preserved ejection fraction and obesity | KCCQ clinical summary score improvement of 7.8 points versus placebo at 52 weeks | Moderate | 2 |
| Hypertension in the context of adiposity | Systolic blood pressure −6.2 mmHg versus −1.1 mmHg with placebo (STEP 1) | Moderate | 2 |
| Metabolic dysfunction-associated steatohepatitis | Resolution of steatohepatitis without worsening of fibrosis in 62.9 % versus 34.3 % with placebo at 72 weeks | Moderate | 1 |
| Obesity in children and adolescents | −16.1 % BMI at 68 weeks versus +0.6 % with placebo | Moderate | 1 |
| Peripheral arterial disease with intermittent claudication | Maximum walking distance ratio to baseline 1.21 versus 1.08 with placebo at 52 weeks | Moderate | 1 |
| Prediabetes and progression to type 2 diabetes | Reversion to normoglycaemia in 84.1 % of participants with prediabetes at baseline versus 47.8 % with placebo (STEP 1) | Low | 2 |
| Sarcopenia and lean-mass preservation during weight reduction | Approximately 39 % of total mass lost was lean mass in the DXA substudy | Low | 1 |
| Effects are reproduced as the contributing trials reported them. Where a confidence interval is held it appears on the per-indication extract rather than in this summary table. | |||
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products. ICH Harmonised Tripartite Guideline 1999;Step 4 version. identifier not held by the Institute
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.