Side Effects of repaglinide: A Synthesis of Findings from 19 Studies

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Original Abstract of the Article

Main Research Findings

Repaglinide is an oral medication used to treat type 2 diabetes by stimulating the release of insulin from the pancreas, particularly during the early stages of insulin release. 13 Repaglinide has been shown to be effective in reducing both fasting and postprandial blood sugar levels, with effects comparable to other commonly used diabetes medications like sulfonylureas, metformin, and glitazones. 12 In combination therapy, repaglinide has also proven to be as effective as other combinations of drugs. 12 Several studies suggest that repaglinide may be particularly beneficial in lowering postprandial blood sugar compared to other medications. 12 Repaglinide has been associated with less weight gain than other diabetes medications like sulfonylureas and glitazones. 12 It is commonly used when metformin is unsuitable due to side effects or ineffective in controlling blood sugar, and it can be particularly helpful for older adults or individuals who need flexible dosing, such as during Ramadan fasting. 12 Repaglinide may be advantageous for diabetic patients with renal impairment as an oral agent. 12 Due to its short duration of action, repaglinide should be taken before each meal, typically at least three times a day. 12 While the effect of repaglinide on total mortality or cardiovascular endpoints has not been studied, several studies suggest potential benefits on cardiovascular risk factors like carotid intima-media thickening, inflammation markers, platelet activation, lipid parameters, endothelial function, adiponectin, and oxidative stress. 12

Reasons for Side Effects

Repaglinide works by blocking ATP-sensitive potassium channels in pancreatic beta cells, which are also present in other tissues, including the heart. 15 This blocking action can lead to various side effects related to both insulin secretion and potential effects on the heart. 15 Additionally, repaglinide might have a direct impact on the pancreas, leading to pancreatitis, possibly due to overstimulation of beta cells. 3

Common Side Effects

Hypoglycemia

Since repaglinide stimulates insulin secretion, it carries a risk of hypoglycemia (low blood sugar). 1 , 12 , 18 Symptoms of hypoglycemia include dizziness, lightheadedness, weakness, confusion, and in severe cases, loss of consciousness. 1

Weight Gain

While repaglinide has been shown to cause less weight gain than sulfonylureas, weight gain can still occur. 12

Gastrointestinal Symptoms

Repaglinide can cause gastrointestinal side effects, such as nausea, vomiting, abdominal pain, and diarrhea. 5

Liver Dysfunction

Some studies suggest that repaglinide might be associated with liver dysfunction. 9 Signs of liver dysfunction include jaundice, loss of appetite, and fatigue. 9

Pancreatitis

There is evidence suggesting that repaglinide may increase the risk of pancreatitis, a serious inflammation of the pancreas. 3 Symptoms of pancreatitis include severe abdominal pain, nausea, and vomiting. 3

Measures to Counteract Side Effects

Hypoglycemia

To prevent hypoglycemia, maintaining a regular eating schedule and engaging in regular exercise are crucial. 1 Your doctor will adjust the dosage of repaglinide according to your individual needs. 1 If you experience symptoms of hypoglycemia, promptly consume sugary foods or drinks like glucose tablets. If symptoms persist, seek immediate medical attention. 1

Weight Gain

Managing weight gain involves adhering to a balanced diet and a regular exercise routine. 12

Gastrointestinal Symptoms

If you experience gastrointestinal discomfort, consult your doctor. 5 They can determine the cause of the symptoms and recommend appropriate treatment. 5

Liver Dysfunction

If you notice signs of liver dysfunction, it is important to seek medical attention immediately. 9 Your doctor will conduct liver function tests and provide necessary treatment. 9

Pancreatitis

If you experience symptoms of pancreatitis, it is crucial to seek immediate medical attention. 3 Your doctor will diagnose pancreatitis and administer appropriate treatment. 3

Comparison Across Studies

Similarities Across Studies

Multiple studies have consistently demonstrated the effectiveness of repaglinide in controlling blood sugar levels. 13 , 10 , 12 , 18 Furthermore, studies have consistently shown that repaglinide causes less weight gain and has a lower risk of hypoglycemia compared to sulfonylurea drugs. 12 , 18

Differences Across Studies

Research on the side effects of repaglinide has yielded mixed results. Some studies suggest that repaglinide can lead to liver dysfunction. 9 Additionally, repaglinide has been linked to the possibility of inducing pancreatitis. 3 These side effects may vary depending on the dosage of repaglinide and individual patient characteristics.

Points to Note for Real-Life Application

Repaglinide is an effective medication for managing type 2 diabetes, but it carries the risk of side effects such as hypoglycemia. 1 , 12 , 15 If taking repaglinide, it is crucial to adhere to your doctor's instructions regarding dosage and timing. 1 Regularly monitoring your blood sugar levels while taking repaglinide is important. 1 If your blood sugar levels are too low, you need to consume sugar. 1 Repaglinide also raises concerns about its impact on the heart. 15 Individuals with heart disease or those who have a history of heart problems should consult their doctor before taking repaglinide. 15

Limitations of Current Research

Research on the side effects of repaglinide is not yet exhaustive and requires further investigation. 5 The long-term effects of repaglinide are not fully understood. 5

Directions for Future Research

Further research on the side effects of repaglinide is needed, especially concerning its long-term impact. 5 Additional research is also required to understand how repaglinide affects the heart. 15

Conclusion

Repaglinide is an effective medication for managing type 2 diabetes but carries a risk of side effects like hypoglycemia. 1 , 12 It is crucial to follow your doctor's instructions regarding dosage and timing when taking repaglinide. 1 Regular blood sugar monitoring is essential while taking repaglinide. 1

Literature analysis of 19 papers
Positive Content
16
Neutral Content
3
Negative Content
0
Article Type
2
0
1
8
18
3.

Repaglinide-Induced Acute Pancreatitis.

Author: UdongwoNdausung, MararenkoAnton, AlchalabiHalah, AminTasnuva, LesniakChristopher, Sharif KhawajaUmar

Pancreatitis treatment
Repaglinide side effect

This case report describes an 84-year-old male who developed acute pancreatitis secondary to repaglinide, a medication for diabetes mellitus. The case highlights the importance of considering medication side effects as a potential cause of acute pancreatitis, even in patients with other risk factors.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

4.

Diabetes and Aging: From Treatment Goals to Pharmacologic Therapy.

Author: LongoMiriam, BellastellaGiuseppe, MaiorinoMaria Ida, MeierJuris J, EspositoKatherine, GiuglianoDario

Diabetes management
Hypoglycemia

This paper reviews glycemic targets and treatment options for older adults with type 2 diabetes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Side effects of frequently used oral antidiabetics on wound healing in vitro.

Author: StuermerEwa Klara, BesserM, TerbergerN, KoesterV, BachmannH S, SeveringA L

Wound healing impairment

Oral antidiabetics can affect skin cells and wound healing. This study found that metformin had the most negative effects on skin cells, while sitagliptin, glibenclamide, and repaglinide had less of an effect.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

6.

Efficacy and risk profile of anti-diabetic therapies: Conventional vs traditional drugs-A mechanistic revisit to understand their mode of action.

Author: GuptaPrachi, BalaManju, GuptaSanjeev, DuaAnita, DaburRajesh, InjetiElisha, MittalAshwani

T2DM management
Side effects

This review explores the mechanisms of action of various anti-diabetic drugs and their potential for combination therapy. It discusses both conventional and herbal strategies, highlighting their benefits and potential side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

In-silico analysis of gymnemagenin from Gymnema sylvestre (Retz.) R.Br. with targets related to diabetes.

Author: RathorePoonam K, ArathyV, AttimaradVijaylaxmi S, KumarPramod, RoySubarna

Anti-diabetic drug

Gymnemagenin, a key constituent of Gymnema sylvestre, is a potential antidiabetic drug. This study uses in silico techniques to predict its drug likeliness against 15 proteins involved in carbohydrate metabolism.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Safety and pharmacokinetics of the CIME combination of drugs and their metabolites after a single oral dosing in healthy volunteers.

Author: LenuzzaNatacha, DuvalXavier, NicolasGrégory, ThévenotEtienne, JobSylvie, VideauOrianne, NarjozCéline, LoriotMarie-Anne, BeaunePhilippe, BecquemontLaurent, MentréFrance, Funck-BrentanoChristian, AlavoineLoubna, ArnaudPhilippe, DelaforgeMarcel, BénechHenri

Accurate PK measurement
Good safety
Phenotyping cocktail
Mild or moderate adverse effects

The CIME combination, a cocktail of ten drugs, showed good safety and accurate pharmacokinetic profiles in healthy volunteers, demonstrating its potential as a phenotyping tool.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

9.

In vitro characterization and invivo toxicity study of repaglinide loaded poly (methyl methacrylate) nanoparticles.

Author: Dhana LekshmiU M, PooviG, KishoreNarra, ReddyP Neelakanta

Diabetes treatment
Reduced side effects

Repaglinide loaded PMMA nanoparticles were formulated to achieve prolonged drug release, reducing the frequency of administration and improving patient compliance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Metabolic effect of repaglinide or acarbose when added to a double oral antidiabetic treatment with sulphonylureas and metformin: a double-blind, cross-over, clinical trial.

Author: DerosaGiuseppe, SalvadeoSibilla A T, D'AngeloAngela, FerrariIlaria, MereuRoberto, PalumboIlaria, MaffioliPamela, RandazzoSabrina, CiceroArrigo F G

Diabetes management

This study aimed to compare the metabolic effects of acarbose and repaglinide in type 2 diabetic patients already on a combination therapy of sulfonylurea and metformin. The primary endpoint was to determine which add-on treatment, acarbose or repaglinide, was more effective in reducing postprandial glucose (PPG). The secondary endpoint was to assess which treatment was more effective in overall glucose homeostasis management.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Defining the role of repaglinide in the management of type 2 diabetes mellitus: a review.

Author: JohansenOdd Erik, BirkelandKåre I

Hyperglycemia control
T2DM treatment
Hypoglycemia

Repaglinide, an insulin secretagogue, is an effective treatment for type 2 diabetes mellitus. It reduces fasting and postprandial hyperglycemia, and its propensity to induce hypoglycemia is similar to or less than that of sulfonylureas.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

13.

Meglitinide analogues for type 2 diabetes mellitus.

Author: BlackC, DonnellyP, McIntyreL, RoyleP L, ShepherdJ P, ThomasS

Glycosylated hemoglobin reduction
Diarrhea
Hypoglycemia
Weight gain

Meglitinide analogues may offer a viable alternative to metformin for managing type 2 diabetes mellitus. This review of 15 randomized controlled trials found that both repaglinide and nateglinide resulted in a significant reduction in glycosylated hemoglobin compared to placebo.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

14.

Twelve weeks' treatment with diazoxide without insulin supplementation in Type 2 diabetes is feasible but does not improve insulin secretion.

Author: RadtkeM, KollindM, QvigstadE, GrillV

Insulin secretion

This study investigated the effects of intermittent diazoxide administration in Type 2 diabetic patients not taking insulin. The results suggest that diazoxide may offer beneficial effects on insulin secretion with limited side effects.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Rationale and options for combination therapy in the treatment of Type 2 diabetes.

Author: Van GaalL F, De LeeuwI H

Type 2 diabetes control
Gastrointestinal side effects

The role of postprandial glucose excursions in the development and progression of vascular complications in Type 2 diabetes was discussed. The development of new agents to control postprandial glucose excursions was suggested as an additional objective for the management of Type 2 diabetes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

19.

Effect of repaglinide on cloned beta cell, cardiac and smooth muscle types of ATP-sensitive potassium channels.

Author: DabrowskiM, WahlP, HolmesW E, AshcroftF M

Diabetes treatment

This study investigated the specificity of repaglinide, a short-acting insulin secretagogue, for three types of cloned ATP-sensitive potassium (KATP) channels. Repaglinide was found to be specific for the beta cell KATP channel, demonstrating its potential as a treatment for type 2 diabetes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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