Investigational Drug Details
| Drug ID: | D154 |
| Drug Name: | Glimepiride |
| Synonyms: | Glimepiride |
| Type: | Chemical drug |
| DrugBank ID: | DB00222 |
| DrugBank Description: | First introduced in 1995, glimepiride is a member of the second-generation sulfonylurea (SU) drug class used for the management of type 2 diabetes mellitus (T2DM) to improve glycemic control. Type 2 diabetes is a metabolic disorder with increasing prevalences worldwide; it is characterized by insulin resistance in accordance with progressive β cell failure and long-term microvascular and macrovascular complications that lead to co-morbidities and mortalities. Sulfonylureas are one of the insulin secretagogues widely used for the management of type 2 diabetes to lower blood glucose levels. The main effect of SUs is thought to be effective when residual pancreatic β-cells are present, as they work by stimulating the release of insulin from the pancreatic beta cells and they are also thought to exert extra-pancreatic effects, such as increasing the insulin-mediated peripheral glucose uptake. Glimepiride works by stimulating the secretion of insulin granules from pancreatic islet beta cells by blocking ATP-sensitive potassium channels (K<SUB>ATP</SUB> channels) and causing depolarization of the beta cells. Compared to , another second SU drug, glimepiride has a longer duration of action. It is sometimes classified as a third-generation SU because it has larger substitutions than other second-generation SUs. Compared to other SUs, glimepiride was associated with a lower risk of developing hypoglycemia and weight gain in clinical trials as well as fewer cardiovascular effects than other SUs due to minimal effects on ischemic preconditioning of cardiac myocytes. It is effective in reducing fasting plasma glucose, postprandial glucose, and glycosylated hemoglobin levels and is considered to be a useful, cost-effective treatment option for managing type 2 diabetes mellitus. Glimepiride was approved by the Food and Drug Administration (FDA) in the United States in 1995 for the treatment of T2DM. It is commonly marketed under the brand name Amaryl as oral tablets and is typically administered once daily. |
| PubChem ID: | 3476 |
| CasNo: | 93479-97-1 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C(=O)(NCCc1ccc(cc1)S(=O)(=O)NC(=O)N[C@H]1CC[C@@H](CC1)C)N1C(=O)C(=C(C1)C)CC |
| Structure: |
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| InChiKey: | WIGIZIANZCJQQY-RUCARUNLSA-N |
| Molecular Weight: | 490.626 |
| DrugBank Targets: | ATP-sensitive inward rectifier potassium channel 11 inhibitor; ATP-sensitive inward rectifier potassium channel 1 inhibitor; ATP-binding cassette sub-family C member 8 inducer |
| DrugBank MoA: | ATP-sensitive potassium channels on pancreatic beta cells that are gated by intracellular ATP and ADP. The hetero-octomeric complex of the channel is composed of four pore-forming Kir6.2 subunits and four regulatory sulfonylurea receptor (SUR) subunits. Alternative splicing allows the formation of channels composed of varying subunit isoforms expressed at different concentrations in different tissues. In pancreatic beta cells, ATP-sensitive potassium channels play a role as essential metabolic sensors and regulators that couple membrane excitability with glucose-stimulated insulin secretion (GSIS). When there is a decrease in the ATP:ADP ratio, the channels are activated and open, leading to K+ efflux from the cell, membrane hyperpolarization, and suppression of insulin secretion. In contrast, increased uptake of glucose into the cell leads to elevated intracellular ATP:ADP ratio, leading to the closure of channels and membrane depolarization. Depolarization leads to activation and opening of the voltage-dependent Ca2+ channels and consequently an influx of calcium ions into the cell. Elevated intracellular calcium levels causes the contraction of the filaments of actomyosin responsible for the exocytosis of insulin granules stored in vesicles. Glimepiride blocks the ATP-sensitive potassium channel by binding non-specifically to the B sites of both sulfonylurea receptor-1 (SUR1) and sulfonylurea receptor-2A (SUR2A) subunits as well as the A site of SUR1 subunit of the channel to promote insulin secretion from the beta cell. |
| DrugBank Pharmacology: | Glimepiride stimulates the secretion of insulin granules from the pancreatic beta cells and improves the sensitivity of peripheral tissues to insulin to increase peripheral glucose uptake, thus reducing plasma blood glucose levels and glycated hemoglobin (HbA1C) levels. A multi-center, randomized, placebo-controlled clinical trial evaluated the efficacy of glimepiride (1–8 mg) as monotherapy titrated over 10 weeks compared with placebo in T2DM subjects who were not controlled by diet alone. In this study, there was a reduction in fasting plasma glucose (FPG) by 46 mg/dL, post-prandial glucose (PPG) by 72 mg/dL, and HbA1c by 1.4% more than the placebo. In another randomized study comprising of patients with T2DM receiving either placebo or one of the three doses (1, 4, or 8 mg) of glimepiride during a 14-week study period, all glimepiride regimens significantly reduced FPG, PPG, and HbA1c values (P < 0.001) compared to placebo by the end of the study period. The 4- and 8-mg doses of glimepiride were more effective than the 1-mg dose; however, the 4-mg dose provided a nearly maximal antihyperglycemic effect. |
| DrugBank Indication: | Glimepiride is indicated for the management of type 2 diabetes in adults as an adjunct to diet and exercise to improve glycemic control as monotherapy. It may also be indicated for use in combination with metformin or insulin to lower blood glucose in patients with type 2 diabetes whose high blood sugar levels cannot be controlled by diet and exercise in conjunction with an oral hypoglycemic (a drug used to lower blood sugar levels) agent alone. |
| Targets: | ABCC8 binder; KCNJ1 inhibitor; KCNJ11 inhibitor; KCNJ11 potassium channel inhibitor |
| Therapeutic Category: | Antidiabetic drug |
| Clinical Trial Progress: | Clinical trial on-going (JPRN-UMIN000016306) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0066 | NCT02649465 | Phase 4 | Completed | No Results Available | November 11, 2015 | July 2, 2021 | Details |
| L0588 | JPRN-UMIN000021291 | Not selected | Not Recruiting | No Results Available | 02/03/2016 | 2 April 2019 | Details |
| L0593 | JPRN-UMIN000020544 | Not selected | Not Recruiting | No Results Available | 13/01/2016 | 21 May 2019 | Details |
| L0739 | CTRI/2019/06/019926 | Post-market | Recruiting | No Results Available | 28/06/2019 | 24 November 2021 | Details |
| L0884 | JPRN-UMIN000016306 | Not selected | Not Recruiting | No Results Available | 27/01/2015 | 2 April 2019 | Details |
| L0906 | JPRN-UMIN000013048 | Not applicable | Not Recruiting | No Results Available | 03/02/2014 | 2 April 2019 | 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 | |
|---|---|---|---|---|
| A07866 | 32329963 | J Diabetes Investig | Comparison of the effects of three kinds of glucose-lowering drugs on non-alcoholic fatty liver disease in patients with type 2 diabetes: A randomized, open-label, three-arm, active control study. | Details |
| A08867 | 31956961 | Diabetes Ther | Study Protocol for Pleiotropic Effects and Safety of Sodium-Glucose Cotransporter 2 Inhibitor Versus Sulfonylurea in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease. | Details |
| A11769 | 30758417 | Rev Assoc Med Bras (1992) | The efficacy of saxagliptin in T2DM patients with non-alcoholic fatty liver disease: preliminary data. | Details |
| A13245 | 30066148 | Diabetologia | Empagliflozin is associated with improvements in liver enzymes potentially consistent with reductions in liver fat: results from randomised trials including the EMPA-REG OUTCOME® trial. | Details |
| A43281 | 32072735 | Diabetes Obes Metab | Dapagliflozin plus saxagliptin add-on to metformin reduces liver fat and adipose tissue volume in patients with type 2 diabetes. | Details |
| A51686 | 34920733 | Cardiovasc Diabetol | Pharmacometabolomic profiles in type 2 diabetic subjects treated with liraglutide or glimepiride. | Details |