Investigational Drug Details
| Drug ID: | D058 |
| Drug Name: | Canagliflozin |
| Synonyms: | Canagliflozin; Canagliflozin anhydrous; Canaglifrozin |
| Type: | Chemical drug |
| DrugBank ID: | DB08907 |
| DrugBank Description: | Canagliflozin, also known as _Invokana_, is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used in the management of type 2 diabetes mellitus along with lifestyle changes including diet and exercise . It was initially approved by the FDA in 2013 for the management of diabetes and later approved in 2018 for a second indication of reducing the risk of cardiovascular events in patients diagnosed with type 2 diabetes mellitus , . Canagliflozin is the first oral antidiabetic drug approved for the prevention of cardiovascular events in patients with type 2 diabetes . Cardiovascular disease is the most common cause of death in these patients . |
| PubChem ID: | 24812758 |
| CasNo: | 842133-18-0 |
| Repositioning for NAFLD: | Yes |
| SMILES: | O[C@H]1[C@@H](O[C@@H]([C@H]([C@@H]1O)O)CO)c1cc(Cc2sc(cc2)c2ccc(cc2)F)c(cc1)C |
| Structure: |
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| InChiKey: | XTNGUQKDFGDXSJ-ZXGKGEBGSA-N |
| Molecular Weight: | 444.524 |
| DrugBank Targets: | Sodium/glucose cotransporter 2 inhibitor |
| DrugBank MoA: | The sodium-glucose co-transporter2 (SGLT2), is found in the proximal tubules of the kidney, and reabsorbs filtered glucose from the renal tubular lumen. Canagliflozin inhibits the SGLT2 co-transporter. This inhibition leads to lower reabsorption of filtered glucose into the body and decreases the renal threshold for glucose (RTG), leading to increased glucose excretion in the urine . |
| DrugBank Pharmacology: | This drug increases urinary glucose excretion and decreases the renal threshold for glucose (RTG) in a dose-dependent manner . The renal threshold is defined as the lowest level of blood glucose associated with the appearance of detectable glucose in the urine . The end result of canagliflozin administration is increased urinary excretion of glucose and less renal absorption of glucose, decreasing glucose concentration in the blood and improving glycemic control. **A note on type 2 diabetes and cardiovascular disease** The risk of cardiovascular events in diabetes type 2 is increased due to the damaging effects of diabetes on blood vessels and nerves in the cardiovascular system. In particular, there is a tendency for hyperglycemia to create pro-atherogenic (plaque forming) lesions in blood vessels, leading to various fatal and non-fatal events including stroke and myocardial infarction . Long-term glycemic control has been proven to be effective in the prevention of cardiovascular events such as myocardial infarction and stroke in patients with type 2 diabetes . |
| DrugBank Indication: | This drug is used in conjunction with diet and exercise to increase glycemic control in adults diagnosed with type 2 diabetes mellitus . Another indication for canagliflozin is the prevention of major cardiovascular events (myocardial infarction, stroke, or death due to a cardiovascular cause) in patients with type 2 diabetes, as well as hospitalization for heart failure in patients with type 2 diabetes. In addition to the above, canagliflozin can be used to lower the risk of end-stage kidney disease and major increases in serum creatinine and cardiovascular death for patients with a combination of type 2 diabetes mellitus, diabetic nephropathy, and albuminuria. It is important to note that this drug is **not** indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis . |
| Targets: | SGLT2 inhibitor |
| Therapeutic Category: | Improve insulin resistance |
| Clinical Trial Progress: | Phase 1 completed (NCT02009488: Canagliflozin improves hepatic insulin sensitivity and insulin secretion and clearance in patients with T2DM. IHTG decreases in proportion to the magnitude of body weight loss, which tended to be greater and occur more often with canagliflozin.) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0467 | JPRN-UMIN000036560 | Not applicable | Recruiting | No Results Available | 01/05/2019 | 12 July 2021 | Details |
| L0591 | JPRN-UMIN000020615 | Not selected | Recruiting | No Results Available | 01/02/2016 | 2 April 2019 | Details |
| L0771 | TCTR20190118008 | Phase 3 | Not Recruiting | No Results Available | 18/01/2019 | 7 February 2022 | Details |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00006 | 35256934 | Acta Pharm Sin B | Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma. | Details |
| A02788 | 34239714 | Oman Med J | Effect of SGLT-2 Inhibitors on Non-alcoholic Fatty Liver Disease among Patients with Type 2 Diabetes Mellitus: Systematic Review with Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials. | Details |
| A03455 | 33994437 | Intern Med | Effects of Canagliflozin on Hepatic Steatosis, Visceral Fat and Skeletal Muscle among Patients with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease. | Details |
| A03789 | 33862461 | Biochem Biophys Res Commun | Canagliflozin ameliorates hepatic fat deposition in obese diabetic mice: Role of prostaglandin E2. | Details |
| A04950 | 33439540 | J Gastroenterol Hepatol | The impact of sodium glucose co-transporter 2 inhibitors on non-alcoholic fatty liver disease. | Details |
| A05042 | 33396949 | Metabolites | Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials. | Details |
| A07543 | 32448832 | Intern Med | SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology. | Details |
| A08104 | 32245205 | Int J Mol Sci | Combined Treatment with Sodium-Glucose Cotransporter-2 Inhibitor (Canagliflozin) and Dipeptidyl Peptidase-4 Inhibitor (Teneligliptin) Alleviates NASH Progression in A Non-Diabetic Rat Model of Steatohepatitis. | Details |
| A08703 | 32017594 | Am J Physiol Endocrinol Metab | Combined effect of canagliflozin and exercise training on high-fat diet-fed mice. | Details |
| A08737 | 32006266 | Adv Exp Med Biol | Glucose Lowering Efficacy and Pleiotropic Effects of Sodium-Glucose Cotransporter 2 Inhibitors. | Details |
| A09583 | 31686884 | Diabetes Metab Syndr Obes | Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors: A Clinician's Guide. | Details |
| A09671 | 31652578 | Int J Mol Sci | The SGLT2 Inhibitor Canagliflozin Prevents Carcinogenesis in a Mouse Model of Diabetes and Non-Alcoholic Steatohepatitis-Related Hepatocarcinogenesis: Association with SGLT2 Expression in Hepatocellular Carcinoma. | Details |
| A10470 | 31324087 | J Assoc Physicians India | Effects of Canagliflozin on Abnormal Liver Function Tests in Patients of Type 2 Diabetes with Non-Alcoholic Fatty Liver Disease. | Details |
| A11204 | 31000862 | J Pak Med Assoc | Expert Opinion: Use of sodium glucose co-transporter type-2 inhibitors in South Asian population -The Pakistan perspective. | Details |
| A11215 | 30993553 | Clin Drug Investig | Effect of Sodium Glucose Co-Transporter 2 Inhibitors on Liver Fat Mass and Body Composition in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus. | Details |
| A12164 | 30577089 | Hepatol Res | Impact of sodium glucose cotransporter 2 inhibitor on histological features and glucose metabolism of non-alcoholic fatty liver disease complicated by diabetes mellitus. | Details |
| A12190 | 30568471 | Diabetes Metab Syndr Obes | Efficacy and safety of canagliflozin in type 2 diabetes mellitus patients with biopsy-proven nonalcoholic steatohepatitis classified as stage 1-3 fibrosis. | Details |
| A12420 | 30461221 | J Diabetes Investig | Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease. | Details |
| A12457 | 30447037 | Diabetes Obes Metab | Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes. | Details |
| A12665 | 30338118 | Obes Sci Pract | Efficacy of canagliflozin against nonalcoholic fatty liver disease: a prospective cohort study. | Details |