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Meglitinide
Drug class
Meglitinide, the prototype of this drug class
Class identifiers
UseType 2 diabetes
ATC codeA10BX
Mode of actioninsulin secretagogue (release stimulator)
Mechanism of actionclose potassium channels of beta cells
Clinical data
Drugs.comDrug Classes
Legal status
In Wikidata

Meglitinides or glinides are a class of drugs used to treat type 2 diabetes.[1]

Drugs

[edit]

Repaglinide (trade name Prandin)[2] gained US Food and Drug Administration approval in 1997.

Other drugs in this class include nateglinide (Starlix)[3] and mitiglinide (Glufast).

Side effects

[edit]

Side effects include weight gain and hypoglycemia. While the potential for hypoglycemia is less than for those on sulfonylureas,[citation needed] it is still a serious potential side effect that can be life-threatening. Patients on this medication should know the signs and symptoms of hypoglycemia and appropriate management.

Repaglinide caused an increased incidence in male rats of benign adenomas (tumors) of the thyroid and liver.[2] No such effect was seen with another drug of this class, nateglinide.[3]

A 2020 Cochrane systematic review did not find enough evidence of reduction of all-cause mortality, serious adverse events, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke or end-stage renal disease when comparing metformin monotherapy to meglitinide for the treatment of type 2 diabetes.[4]

Mechanism of action

[edit]

They bind to an ATP-dependent K+ (KATP) channel on the cell membrane of pancreatic beta cells in a similar manner to sulfonylureas but have a weaker binding affinity and faster dissociation from the SUR1 binding site. This increases the concentration of intracellular potassium, which causes the electric potential toward the intracellular side of the membrane to become more positive. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granula in the cell membrane, and therefore increased secretion of (pro) insulin.

References

[edit]
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Meglitinide

View on Grokipedia
from Grokipedia
Meglitinides are a class of oral antidiabetic medications used primarily to manage type 2 diabetes mellitus by stimulating the rapid release of insulin from pancreatic beta cells in response to meals. These short-acting agents, which include repaglinide, nateglinide, and mitiglinide, are structurally distinct from sulfonylureas but share a similar mechanism of action, binding to the sulfonylurea receptor 1 (SUR1) subunit of ATP-sensitive potassium (KATP) channels on beta cells. This binding closes the KATP channels, leading to membrane depolarization, calcium influx, and subsequent insulin exocytosis, particularly enhancing the early-phase insulin response to control postprandial hyperglycemia. Repaglinide, approved by the FDA in 1997, and nateglinide, approved in 2000, are typically administered shortly before meals to mimic physiological insulin secretion patterns and minimize the risk of prolonged hypoglycemia compared to longer-acting alternatives. As adjuncts to diet and exercise, meglitinides are effective for improving glycemic control in patients with type 2 diabetes but may cause adverse effects such as hypoglycemia, weight gain, and gastrointestinal upset, with contraindications in type 1 diabetes or diabetic ketoacidosis. Their rapid absorption and hepatic metabolism contribute to their utility in flexible dosing regimens, though drug interactions involving CYP3A4 enzymes can influence efficacy and safety.

Overview

Definition and classification

Meglitinides are a class of oral hypoglycemic agents classified as insulin secretagogues, primarily used in the management of mellitus by stimulating insulin release from pancreatic beta cells. They function as antihyperglycemic medications that help lower blood glucose levels, particularly in patients requiring enhanced endogenous insulin production. Known alternatively as glinides or non-sulfonylurea meglitinides, this is structurally distinct from , despite sharing a comparable ability to promote insulin secretion. The prototype compound, meglitinide, is a derivative that serves as the foundational structure for agents in this category, exemplifying their chemical basis as short-acting oral antidiabetics. In the Anatomical Therapeutic Chemical (ATC) classification system, meglitinides fall under the code A10BX, encompassing other blood glucose-lowering drugs excluding insulins. A key distinguishing feature of meglitinides is their short duration of action, typically with a of about one hour, which allows them to effectively target postprandial without prolonged effects on glucose. This rapid onset and offset profile differentiates them from longer-acting insulin secretagogues, enabling more precise control over meal-related glucose excursions.

Therapeutic role in diabetes management

Meglitinides serve as an adjunct to diet and exercise for improving glycemic control in adults with mellitus, particularly targeting postprandial through their rapid stimulation of insulin secretion. Classified as glinides, they are oral agents that mimic physiological insulin release in response to meals, making them suitable for patients with irregular eating patterns. Compared to , meglitinides have a shorter duration of action, which reduces the risk of prolonged , although both classes carry a higher incidence than metformin. Unlike metformin, which is recommended as first-line due to its established cardiovascular benefits and weight-neutral profile, meglitinides are not initial choices but are valuable in combination regimens, such as with metformin or thiazolidinediones, to address residual postprandial glucose excursions. Their rapid onset allows for precise timing with meals, offering an advantage in managing meal-related glucose spikes over longer-acting agents. Meglitinides may help preserve beta-cell function more effectively than by promoting pulsatile insulin release without sustained , potentially slowing beta-cell exhaustion in early . However, a 2007 Cochrane review found no evidence of benefits on cardiovascular events or all-cause mortality compared to or metformin, limiting their role to glycemic management without broader outcome improvements. Meglitinides are contraindicated in and , as these conditions require insulin therapy, and they offer no utility in insulin-deficient states.

Pharmacology

Mechanism of action

Meglitinides exert their effects by binding to the sulfonylurea receptor 1 (SUR1) subunit of ATP-sensitive (K-ATP) channels located on the surface of pancreatic beta cells. This interaction inhibits the activity of these channels, which are composed of inward-rectifier channels (Kir6.2) and SUR1 regulatory subunits, thereby reducing efflux from the cell. The closure of K-ATP channels causes membrane , which activates voltage-gated calcium channels. This leads to an influx of extracellular calcium ions into the , elevating intracellular calcium levels. The rise in calcium concentration promotes the fusion of insulin-containing secretory granules with the plasma membrane, resulting in and the rapid release of insulin, with a particular emphasis on enhancing the early-phase insulin secretion response to stimuli. In comparison to , which share a similar overall pathway, meglitinides demonstrate higher binding affinity for SUR1 but with shorter dissociation kinetics, enabling a more transient channel inhibition. This pharmacokinetic profile supports a pulsatile pattern of insulin closely aligned with meal ingestion, mimicking physiological postprandial responses. Meglitinides have no direct influence on peripheral insulin sensitivity or on the of other hormones, such as , from pancreatic alpha cells.

Pharmacokinetics

Meglitinides, including and , are characterized by rapid oral absorption following administration, with typically occurring within 15 to 30 minutes and peak plasma concentrations reached in approximately 1 hour. This quick absorption profile supports their use as short-acting insulin secretagogues timed with meals. For , absorption is rapid and complete from the , with peak levels at 30 to 60 minutes after dosing. Similarly, achieves peak plasma levels within 1 hour, though the rate may be slightly delayed when taken with , without altering the overall extent of absorption. The of meglitinides is high, with exhibiting a mean absolute of 56% and approximately 73%. Both agents demonstrate extensive protein binding, exceeding 98% primarily to , which contributes to their distribution characteristics and limits free drug availability in plasma. Metabolism of meglitinides occurs primarily in the liver through enzymes, with minimal formation of active metabolites. Repaglinide is metabolized mainly by and CYP2C8, undergoing oxidative to inactive polar metabolites. Nateglinide is predominantly metabolized by (about 70%) and (30%), via and conjugation, resulting in mostly inactive compounds. Elimination of meglitinides is rapid, reflected in their short plasma half-lives of about 1 hour, which underpins their transient pharmacodynamic effects. has a of 1 to 1.4 hours, with over 90% excreted in via biliary elimination and less than 8% in . exhibits a of approximately 1.5 hours, with 83% recovered in (16% as unchanged drug) and 10% in , showing no accumulation with repeated dosing. Factors such as hepatic impairment can prolong exposure and effects, with increased area under the curve observed in mild for both agents, necessitating dose adjustments. Renal impairment generally does not significantly alter in moderate cases, though caution is advised in severe renal dysfunction or dialysis. Food intake does not substantially affect the extent of absorption (as measured by AUC) but may reduce peak concentrations and delay time to peak for both and .

Clinical use

Indications and efficacy

Meglitinides are approved by the U.S. Food and Drug Administration (FDA) and the (EMA) for the treatment of mellitus in adults as monotherapy or in combination with metformin (and thiazolidinediones for ), specifically when cannot be adequately controlled by diet, exercise, and weight reduction alone. Clinical trials demonstrate that meglitinides reduce HbA1c by 0.5% to 1.5% compared to , with particularly effective control of postprandial glucose excursions due to their rapid of early-phase insulin , outperforming agents primarily targeting glucose levels. A 2007 Cochrane of 11 randomized controlled trials involving and versus confirmed significant improvements in glycemic control, including HbA1c , but found no of reduced all-cause mortality or cardiovascular events. When compared to , meglitinides show comparable overall HbA1c lowering but provide a more physiologic early insulin response pattern, potentially reducing prolonged risk. In , meglitinides with metformin yield additive HbA1c reductions of approximately 1.0% to 1.5% beyond metformin monotherapy, enhancing both and postprandial control. Data on combinations with thiazolidinediones remain limited, with few trials reporting modest additional glycemic benefits but insufficient evidence for routine recommendation. Long-term use of meglitinides may offer potential for beta-cell function preservation compared to , based on experimental and observational data suggesting less exhaustion of , though large-scale confirmation is lacking. However, major cardiovascular outcomes trials, such as the study for , have shown no reduction in macrovascular events or mortality, indicating neutral cardiovascular safety without protective benefits.

Dosage and administration

Meglitinides are typically administered orally two to three times daily, with dosing timed 15 to 30 minutes before to align with their rapid , which stimulates insulin secretion in response to prandial glucose loads. If a is skipped, the corresponding dose should also be omitted to prevent . This flexible regimen allows for adjustment based on the patient's meal pattern, such as up to four doses per day if additional meals are consumed. Initial dosing for meglitinides starts at 0.5 mg (or 1–2 mg if HbA1c ≥8%) for or 120 mg (or 60 mg if near glycemic goal) for before each meal, with upward in increments based on glycemic response, typically not exceeding 4 mg or 120 mg per dose, respectively, and a daily maximum of 16 mg or 360 mg. Dose adjustments should occur after at least one week of , guided by monitoring of plasma glucose and HbA1c levels to achieve target control. For , in patients with renal impairment (e.g., creatinine clearance 20-40 mL/min) or hepatic dysfunction, begins at the lowest dose (0.5 mg) with cautious and prolonged intervals between increases to mitigate accumulation risks; no renal adjustment is needed for , though caution is advised in moderate-to-severe hepatic impairment. These agents are available exclusively in oral tablet formulations. Patient education emphasizes strict adherence to pre-meal timing and meal consistency, as deviations can lead to suboptimal glucose control or hypoglycemic episodes; regular self-monitoring of blood glucose is advised, particularly during dose adjustments or illness.

Specific agents

Repaglinide

is the prototypical agent in the meglitinide class of oral antidiabetic drugs, structurally classified as a carbamoyl derivative with the chemical name S(+)2-ethoxy-4(2((3-methyl-1-(2-(1-piperidinyl)phenyl)-butyl)amino)-2-oxoethyl) and molecular formula C27H36N2O4. Marketed under the brand name Prandin and widely available in generic forms, it is prescribed for managing mellitus by targeting postprandial through rapid stimulation of insulin secretion from pancreatic beta cells. Its pharmacokinetic profile is characterized by rapid absorption and short duration of action, with a plasma half-life of approximately 1 hour, making it suitable for pre-meal dosing. undergoes extensive hepatic metabolism primarily via the enzymes and CYP2C8, with over 90% of the dose excreted in the feces through biliary elimination and minimal renal clearance (less than 8%). This profile contributes to its lower risk of accumulation compared to longer-acting . In clinical studies, repaglinide monotherapy has demonstrated HbA1c reductions of up to 1.7–2.1%, with comparative trials showing greater efficacy than (mean reduction of -1.17% versus -0.81%). It has demonstrated enhanced efficacy in with (a ), with additional HbA1c reduction of approximately 0.6–1.0%. Repaglinide received FDA approval in 1997 and is one of the most commonly used meglitinides globally, available in numerous countries for management.

Nateglinide

Nateglinide is a D-phenylalanine derivative with the chemical name (-)-N-[(trans-4-isopropylcyclohexane)carbonyl]-D-phenylalanine and a molecular weight of 317.43 g/mol. It is marketed under the brand name Starlix and is also available in generic formulations. Nateglinide exhibits unique suited for rapid insulin secretion, with an within 20 minutes, a plasma of approximately 1.5 hours, and predominant renal (83% in , with about 16% as unchanged ). This short duration and quick reversal allow for precise timing with meals, peaking insulin secretion around 1 hour post-dose and returning to baseline by 4 hours, which supports its role in targeting early postprandial glucose excursions. In terms of efficacy, reduces HbA1c by approximately 0.4% to 0.8% as monotherapy and up to 1.9% when combined with metformin, with particular strength in controlling postprandial due to its faster onset compared to other meglitinides. However, it demonstrates less overall glycemic potency than , which achieves greater HbA1c reductions (e.g., 1.57% versus 1.04% in comparative studies), making nateglinide better suited for scenarios emphasizing rapid, meal-specific insulin response rather than sustained effects. The U.S. Food and Drug Administration approved nateglinide in December 2000 for use in type 2 diabetes management, often as an adjunct to diet and exercise or in combination therapy with agents like metformin or thiazolidinediones to enhance glycemic control without added benefit from sulfonylureas.

Mitiglinide

Mitiglinide is a meglitinide-class oral antidiabetic drug structurally classified as a benzylamine derivative, featuring a benzyl group in its core structure (2S-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate calcium salt). This compound stimulates insulin secretion from pancreatic β-cells by binding to ATP-sensitive potassium channels, with a high selectivity for the SUR1/Kir6.2 complex over cardiac or vascular isoforms. In clinical practice, mitiglinide is marketed primarily in under brand names such as Glufast (in ), Bokangtai (in ), and Kuai ru tuo (also in ), reflecting its regional focus for management. Mitiglinide demonstrates unique pharmacokinetic properties suited for targeting postprandial glucose excursions, with an ultra-rapid occurring in less than 15 minutes after , enabling prompt insulin release aligned with ingestion. Its plasma is short, approximately 1.5 hours, which contributes to its transient effect and reduced risk of prolonged compared to longer-acting agents. The drug undergoes hepatic metabolism primarily via by uridine 5'-diphospho-glucuronosyltransferase enzymes, with renal excretion of metabolites, and food affects the rate but not the extent of its absorption. In terms of efficacy, mitiglinide provides HbA1c reductions of about 1% in Japanese patients with , comparable to other meglitinides, while particularly excelling in postprandial glucose control due to its rapid kinetics. It was specifically approved in in 2002 for improving postprandial in this population, where it is often used in combination therapies to mimic physiological insulin secretion patterns. Outside , its availability remains limited, and it has not received approval from the U.S. (FDA).

Adverse effects

Common side effects

The most common side effect of meglitinides is , occurring in 10-30% of patients depending on dosing and , with incidences ranging from 17-44% for and 11-23% for in clinical trials compared to . This risk is meal-dependent due to the drugs' rapid onset and short duration of action, which stimulates insulin release primarily in response to prandial glucose loads, though it can still lead to symptomatic episodes such as shakiness, sweating, or if meals are skipped or doses misaligned. Weight gain is another frequent adverse effect, typically amounting to 1-3 kg over 6 months of treatment, attributed to the insulin-mediated promotion of anabolic processes like and reduced glucose excretion. For , mean weight increases of up to 2.1 kg have been observed in monotherapy, while shows gains of about 1-1.6 kg, particularly when combined with other agents. Gastrointestinal disturbances, including upper GI symptoms such as , , and dyspepsia, affect 5-10% of users. occurs in approximately 5% of repaglinide-treated patients, in 2-5%, and similar rates (around 3%) are seen with , often resolving with continued use or dose adjustment. Other common mild effects include (10-11% with ), arthralgia (3-6%), and (4-5%), which are generally self-limiting and occur at rates comparable to in trials. Overall, the side effect profile of meglitinides is similar to that of but may involve a potentially lower incidence of due to their shorter duration of action.

Serious risks and contraindications

Meglitinides, like other insulin secretagogues, carry a risk of severe , which can manifest as seizures, , or other neurological impairments, necessitating immediate medical intervention such as hospitalization and intravenous glucose administration. This risk is heightened in elderly patients, those with renal impairment (e.g., advanced ), or hepatic dysfunction due to altered drug clearance and prolonged exposure. Management involves prompt recognition of symptoms like , sweating, or tremors, followed by oral or parenteral glucose, with close monitoring to prevent recurrence. Cardiovascular risks with meglitinides are generally low, with clinical trials showing no significant increase in major events compared to or other agents, though caution is advised in patients with heart disease due to potential exacerbation from hypoglycemia-induced stress. In particular, with thiazolidinediones has been associated with and congestive in a small subset of patients (approximately 0.8%), primarily those with preexisting , warranting avoidance in New York Heart Association (NYHA) class III or IV . Overall, meglitinides appear to have a more favorable cardiovascular profile than , with reduced risk of or in observational data. Drug interactions pose significant risks due to meglitinides' hepatic metabolism primarily via (repaglinide also via CYP2C8), leading to elevated plasma levels and heightened when co-administered with strong inhibitors such as or , which can increase exposure by up to 1.4-fold. Concomitant use of is contraindicated with , as it dramatically elevates AUC by 8.1-fold through CYP2C8 inhibition, substantially increasing severe risk. Inducers like rifampin may reduce efficacy by decreasing levels, requiring dose adjustments and glucose monitoring. Key contraindications for meglitinides include type 1 diabetes mellitus, (with or without coma), and known to the agent or its components, as these conditions necessitate insulin therapy. Cross-reactivity with sulfa allergies is rare, as meglitinides lack structure, though caution is advised in patients with such history. For specifically, co-administration with or certain other CYP inhibitors is prohibited. Current FDA labeling provides a summary for use in : Limited available human data do not identify a drug-associated of major birth defects, , or other adverse maternal or fetal outcomes. Animal reproduction studies showed no teratogenicity in rats or rabbits at exposures up to 60 times the clinical dose for and similar findings for . Use during only if the potential benefit justifies the potential to the , with insulin preferred for glycemic control. is not recommended due to unknown excretion in human milk.

History

Development

Meglitinides originated from efforts to develop improved insulin secretagogues beyond , with serving as the foundational compound in this class. Precursor drugs to were invented in late 1983 by scientists at Dr. Karl Thomae GmbH, a German pharmaceutical company and subsidiary of , based on a meglitinide prototype designed to enhance binding affinity to the receptor while addressing limitations of earlier agents such as prolonged action and risk. This structural modification aimed to create a more for glycemic control in . The research focus for meglitinides centered on developing short-acting insulin secretagogues that could more closely mimic the physiologic insulin response, thereby reducing post hyperglycemia without causing sustained insulin release. In the , pre-clinical studies identified the binding of these agents to the receptor 1 (SUR1) subunit of ATP-sensitive potassium channels in pancreatic beta cells, facilitating rapid closure of these channels and insulin exocytosis. Animal studies demonstrated that effectively lowered post glucose excursions in rodent and dog models while minimizing the risk of prolonged , due to its short plasma half-life and tissue distribution profile. Nateglinide emerged in the late as another key meglitinide, derived from D-phenylalanine analogs to further optimize rapid-onset insulin secretion. Developed by Co., Inc., in collaboration with F. Hoffmann-La Roche, nateglinide was engineered as a non-sulfonylurea meglitinide with enhanced selectivity for SUR1, allowing for quicker dissociation from the receptor and an even shorter duration of action compared to . Mitiglinide, an ultra-short-acting meglitinide, was developed in by Kissei Pharmaceutical Co., Ltd., building on the class's principles to provide precise control over mealtime glucose spikes. Synthesized as a benzylsuccinic acid derivative, it was designed for maximal beta-cell stimulation with minimal carryover effects, undergoing initial pre-clinical evaluation in the to confirm its potency in animal models of postprandial .

Regulatory approvals

Meglitinides, a class of oral antidiabetic agents, have undergone regulatory scrutiny primarily through their individual agents, with approvals centered on their use in managing mellitus. , originally developed by and licensed to , saw its (NDA 20-741) filed with the U.S. (FDA) in July 1997. The FDA granted approval for (marketed as Prandin) on December 22, 1997, for the treatment of as an adjunct to diet and exercise. This approval marked as the first meglitinide available in the United States, based on clinical data demonstrating its rapid stimulation of insulin secretion from pancreatic beta cells. Nateglinide, developed by in collaboration with and marketed by , received FDA approval on December 22, 2000, under the brand name Starlix (NDA 21-204), also for management in adults, either as monotherapy or in combination with other agents like metformin. The approval followed demonstration of its short-acting insulinotropic effects, particularly for controlling postprandial . Mitiglinide, the third meglitinide, was approved in by the (PMDA) on January 29, 2004, as Glufast for treatment. It has not received approval from the FDA and has limited regulatory status in , with no centralized (EMA) authorization, restricting its availability primarily to the Japanese market. Following expiration, repaglinide's core composition s (U.S. Patents 5,216,167 and 5,312,924) ended on March 14, 2009, after a pediatric exclusivity extension, enabling generic entry in various markets. A related method-of-use (U.S. Patent 6,677,358) for expired on June 12, 2018, further broadening generic availability globally; for instance, the first U.S. generic approvals occurred around 2013, with market launches by 2014. Post-marketing surveillance led to significant label updates for . In 2010, the FDA revised the Prandin label to contraindicate its use with due to pharmacokinetic interactions that substantially increase exposure—up to eightfold—raising the risk of severe ; this change was mirrored in updates to the (Lopid) label. Similar precautions were added for other CYP2C8 inhibitors.

References

  1. https://www.ncbi.nlm.nih.gov/books/NBK482386/
  2. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(01)06715-0/fulltext
  3. https://www.ncbi.nlm.nih.gov/books/NBK559305/
  4. https://pmc.ncbi.nlm.nih.gov/articles/PMC3832818/
  5. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020741s041s042lbl.pdf
  6. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021204s025lbl.pdf
  7. https://www.ncbi.nlm.nih.gov/books/NBK548161/
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC6116761/
  9. https://pmc.ncbi.nlm.nih.gov/articles/PMC7389480/
  10. https://pubchem.ncbi.nlm.nih.gov/compound/Meglitinide
  11. https://atcddd.fhi.no/atc_ddd_index/?code=A10BX&showdescription=no
  12. https://pmc.ncbi.nlm.nih.gov/articles/PMC5652839/
  13. https://www.ncbi.nlm.nih.gov/books/NBK279141/
  14. https://pubmed.ncbi.nlm.nih.gov/16735959/
  15. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020741s035lbl.pdf
  16. https://pubmed.ncbi.nlm.nih.gov/10522840/
  17. https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/20741s13lbl.pdf
  18. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/077463s000lbl.pdf
  19. https://www.ema.europa.eu/en/documents/product-information/prandin-epar-product-information_en.pdf
  20. https://pubmed.ncbi.nlm.nih.gov/33106149/
  21. https://www.acpjournals.org/doi/10.7326/0003-4819-147-6-200709180-00178
  22. https://www.medicaid.nv.gov/Downloads/provider/Meglitinides_2019-09.pdf
  23. https://pubmed.ncbi.nlm.nih.gov/20228402/
  24. https://hopkinsdiabetesinfo.org/medications-for-type-2-diabetes-sulfonylureas-and-meglitinides/
  25. https://www.drugs.com/dosage/metformin-repaglinide.html
  26. https://reference.medscape.com/drug/prandin-repaglinide-342718
  27. https://www.drugs.com/dosage/nateglinide.html
  28. https://pubmed.ncbi.nlm.nih.gov/22268393/
  29. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020741s044lbl.pdf
  30. https://pubmed.ncbi.nlm.nih.gov/24843581/
  31. https://pmc.ncbi.nlm.nih.gov/articles/PMC3960773/
  32. https://pmc.ncbi.nlm.nih.gov/articles/PMC11207096/
  33. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-204_Stsrlix.cfm
  34. https://pubchem.ncbi.nlm.nih.gov/compound/Mitiglinide
  35. https://pmc.ncbi.nlm.nih.gov/articles/PMC1572697/
  36. https://www.kissei.co.jp/e_contents/news/2006/20061030-697.html
  37. https://finance.yahoo.com/news/uni-bio-science-launches-best-140928016.html
  38. https://www.eisai.com/news/news201045.html
  39. https://www.jstage.jst.go.jp/article/fpj/124/4/124_4_245/_article
  40. https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-017-0161-6
  41. https://clinicaltrials.gov/study/NCT04349696
  42. https://www.jstage.jst.go.jp/article/endocrj/56/6/56_K09E-023/_pdf
  43. https://pubmed.ncbi.nlm.nih.gov/15293870/
  44. https://www.metabolismjournal.com/article/S0026-0495%252822%252900210-4/pdf
  45. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021204s015lbl.pdf
  46. https://bjd-abcd.com/index.php/bjd/article/download/1003/1237/9293
  47. https://pubmed.ncbi.nlm.nih.gov/9739505/
  48. https://onlinelibrary.wiley.com/doi/abs/10.1002/9781118387658.ch42
  49. https://adisinsight.springer.com/drugs/800000002
  50. https://go.drugbank.com/drugs/DB01252
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