Investigational Drug Details
| Drug ID: | D327 |
| Drug Name: | Semaglutide |
| Synonyms: | Semaglutide |
| Type: | Chemical drug |
| DrugBank ID: | DB13928 |
| DrugBank Description: | Semaglutide is a glucagon-like peptide 1 (GLP-1) analog used to manage type 2 diabetes along with lifestyle changes, such as dietary restrictions and increased physical activity. Other members of this drug class include and . Semaglutide was developed by Novo Nordisk and approved by the FDA for subcutaneous injection in December 2017. The tablet formulation was approved for oral administration in September 2019. Semaglutide works by binding to and activating the GLP-1 receptor, thereby stimulating insulin secretion and reducing blood glucose. The subcutaneous injection is administered once weekly and the tablet is administered once a day. Semaglutide offers a competitive advantage over other drugs used to manage diabetes, which may require several daily doses. Clinical trials have determined that this drug reduces glycosylated hemoglobin (HbA1c) levels and reduces body weight, proving to be effective for patients with type 2 diabetes. In June 2021, semaglutide was approved by the FDA for chronic weight management in adults with general obesity or overweight who have at least one weight-related condition: this marks semaglutide as the first approved drug for such use since 2014. Health Canada also approved semaglutide in November 2021 for the treatment of adults with obesity. |
| PubChem ID: | 56843331 |
| CasNo: | 910463-68-2 |
| Repositioning for NAFLD: | Yes |
| SMILES: | O=C(N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)C(NC(=O)[C@@H](N)Cc1[nH]cnc1)(C)C)CCC(=O)O)[C@H](O)C)Cc1ccccc1)[C@H](O)C)CO)CC(=O)O)C(C)C)CO)CO)Cc1ccc(O)cc1)CC(C)C)CCC(=O)O)CCC(=O)N)C)C)CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)CCC(=O)O)Cc1ccccc1)[C@H](CC)C)C)Cc1c2c([nH]c1)cccc2)CC(C)C |
| Structure: |
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| InChiKey: | DLSWIYLPEUIQAV-CCUURXOWSA-N |
| Molecular Weight: | 4113.641 |
| DrugBank Targets: | Glucagon-like peptide 1 receptor agonist |
| DrugBank MoA: | **Mechanism of glycemic control** GLP-1 is a physiological hormone that promotes glycemic control via several different mechanisms, including insulin secretion, slowing gastric emptying, and reducing postprandial glucagon secretion. The homeostasis of glucose is dependent on hormones such as insulin and amylin, which are secreted by the beta cells of the pancreas. Semaglutide is 94% similar to human GLP-1. Analogs of this hormone such as semaglutide stimulate the synthesis of insulin by stimulating pancreatic islet cells and reducing glucagon secretion. They directly bind with selectivity to the GLP-1 receptor, causing various beneficial downstream effects that reduce blood glucose in a glucose-dependent fashion. **Mechanism of cardiovascular benefit and weight loss** In hypercholesterolemia, semaglutide is believed to reduce the progression of atherosclerosis via decreased gut permeability and decreased inflammation. Weight loss is believed to occur via the reduction of appetite and food cravings after semaglutide administration. |
| DrugBank Pharmacology: | Semaglutide reduces HbA1c, systolic blood pressure, and body weight. After 12 weeks of treatment, semaglutide decreased fasting and postprandial glucose by increasing insulin production and decreasing glucagon secretion (which is normally associated with increases in blood sugar). Semaglutide also lowers fasting triglycerides and VLDL cholesterol, exerting beneficial effects on cardiovascular health. Semaglutide has been shown to cause medullary thyroid cell carcinoma in rodents. While its clinical relevance to humans is unknown, the FDA advises not to administer this drug in those with a personal or family history of medullary thyroid carcinoma. Semaglutide also poses a risk of pancreatitis and dehydration. Patients must be adequately hydrated while on semaglutide and are advised to seek medical attention immediately in cases of abdominal pain radiating to the back. Because this drug delays gastric emptying, it is important to monitor for the efficacy or adverse effects of other drugs that are administered orally. |
| DrugBank Indication: | Semaglutide is indicated to improve glycemic control in adults diagnosed with type 2 diabetes mellitus, and is used as an adjunct to diet and exercise. However, semaglutide is not a suitable first-line drug for diabetes that has not been controlled by diet and exercise. In addition, it has not been studied in patients with pancreatitis. Semaglutide is not intended for use in patients with type 1 diabetes or to treat diabetic ketoacidosis. Semaglutide is indicated for chronic weight management in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol), for use in addition to a reduced-calorie diet and increased physical activity. |
| Targets: | GLP1R agonist |
| Therapeutic Category: | Antidiabetic drug |
| Clinical Trial Progress: | Phase 2 completed (This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT02970942.).) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0036 | NCT03884075 | Phase 2 | Recruiting | No Results Available | July 24, 2019 | March 18, 2022 | Details |
| L0038 | NCT04944992 | Phase 2 | Active, not recruiting | No Results Available | August 4, 2021 | March 4, 2022 | Details |
| L0057 | NCT04216589 | Phase 2 | Recruiting | No Results Available | October 1, 2020 | January 31, 2022 | Details |
| L0079 | NCT03357380 | Phase 1 | Completed | No Results Available | November 28, 2017 | November 22, 2021 | Details |
| L0080 | NCT05067621 | Phase 3 | Not yet recruiting | No Results Available | June 2022 | February 10, 2022 | Details |
| L0162 | NCT04639414 | Phase 4 | Recruiting | No Results Available | March 26, 2021 | January 20, 2022 | Details |
| L0187 | NCT03987451 | Phase 2 | Completed | No Results Available | June 18, 2019 | December 1, 2021 | Details |
| L0190 | NCT04822181 | Phase 3 | Recruiting | No Results Available | April 1, 2021 | March 11, 2022 | Details |
| L0192 | NCT05016882 | Phase 2 | Recruiting | No Results Available | August 31, 2021 | March 15, 2022 | Details |
| L0196 | NCT04971785 | Phase 2 | Recruiting | No Results Available | August 9, 2021 | March 11, 2022 | Details |
| L0198 | NCT03987074 | Phase 2 | Completed | Has Results | July 29, 2019 | July 15, 2021 | Details |
| L0228 | NCT02970942 | Phase 2 | Completed | Has Results | November 30, 2016 | November 16, 2021 | Details |
| L0323 | NCT05195944 | Phase 4 | Not yet recruiting | No Results Available | April 2022 | January 19, 2022 | Details |
| L0383 | EUCTR2020-003566-39-IT | Phase 2 | Authorised | No Results Available | 07/06/2021 | 30 August 2021 | Details |
| L0744 | EUCTR2018-004484-31-ES | Phase 2 | Authorised | No Results Available | 24/05/2019 | 30 June 2019 | Details |
| L0752 | NCT03919929 | Phase 2/Phase 3 | Recruiting | No Results Available | 15/04/2019 | 7 June 2021 | Details |
| L0769 | EUCTR2018-004484-31-GB | Phase 2 | Authorised | No Results Available | 31/01/2019 | 10 December 2019 | Details |
| L0845 | EUCTR2016-000685-39-GB | Phase 2 | Not Recruiting | No Results Available | 22/07/2016 | 8 June 2020 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00305 | 35143711 | Clin Transl Sci | Hepatoprotective effects of semaglutide, lanifibranor and dietary intervention in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH. | Details |
| A00609 | 35030323 | Lancet Gastroenterol Hepatol | Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review. | Details |
| A01853 | 34588764 | Drug Des Devel Ther | Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease. | Details |
| A01894 | 34570916 | Aliment Pharmacol Ther | Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. | Details |
| A02194 | 34465857 | Int J Obes (Lond) | Obese mice weight loss role on nonalcoholic fatty liver disease and endoplasmic reticulum stress treated by a GLP-1 receptor agonist. | Details |
| A02287 | 34435378 | Aliment Pharmacol Ther | Systematic review with network meta-analysis: comparative efficacy of pharmacologic therapies for fibrosis improvement and resolution of NASH. | Details |
| A02349 | 34406410 | J Clin Endocrinol Metab | The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD. | Details |
| A03013 | 34164242 | Cureus | Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Non-Alcoholic Steatohepatitis: A Clinical Review Article. | Details |
| A04749 | 33515800 | Ann Hepatol | Horizon scanning of therapeutic modalities for nonalcoholic steatohepatitis. | Details |
| A04758 | 33513761 | Metabolites | Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. | Details |
| A04924 | 33447122 | Clin Med Insights Endocrinol Diabetes | Oral GLP1 Analog: Where Does the Tide Go? | Details |
| A05624 | 33185364 | N Engl J Med | A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. | Details |
| A06005 | 33039693 | Contemp Clin Trials | Semaglutide for the treatment of non-alcoholic steatohepatitis: Trial design and comparison of non-invasive biomarkers. | Details |
| A06147 | 32987188 | Mol Metab | Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. | Details |
| A08113 | 32243137 | Bioconjug Chem | New Generation Oxyntomodulin Peptides with Improved Pharmacokinetic Profiles Exhibit Weight Reducing and Anti-Steatotic Properties in Mice. | Details |
| A08128 | 32237916 | Expert Opin Pharmacother | Current and new pharmacotherapy options for non-alcoholic steatohepatitis. | Details |
| A10476 | 31321014 | Ther Adv Chronic Dis | Effects of glucagon-like peptide 1 receptor agonists on comorbidities in older patients with diabetes mellitus. | Details |
| A10662 | 31246368 | Aliment Pharmacol Ther | Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity. | Details |
| A11125 | 31031702 | Front Endocrinol (Lausanne) | The Discovery and Development of Liraglutide and Semaglutide. | Details |
| A14182 | 29547706 | Atherosclerosis | Clinical implications of current cardiovascular outcome trials with sodium glucose cotransporter-2 (SGLT2) inhibitors. | Details |