Academic literature on the topic 'Gliclazide Side effects'

The lists of essential medicines of the World Health Organization (WHO) and Brazil include gliclazide as an alternative to the oral antidiabetic drug of first choice, metformin, in the treatment of type 2 diabetes mellitus because of its pharmacokinetic profile and few side effects. Thus, it is also considered by WHO and the International Pharmaceutical Federation (FIP) as a drug candidate to biowaiver, which is the evaluation of how favorable the biopharmaceutics characteristics are in order to obtain waiver from the relative bioavailability/bioequivalence (RB/BE) studies to register new medicines. This paper presents a review about the solubility, permeability and dissolution of gliclazide. A critical analysis of the information allowed to identify gliclazide as a Biopharmaceutics Classification System (BCS) Class II drug. Therefore, new drugs in immediate release dosage forms will not be eligible for biowaiver. Regarding the extended release dosage forms, besides the limited solubility, no information on the comparative dissolution profile was found, which would be necessary to analyze a possible biowaiver for a smaller dosage. It can be concluded that the registration of new medicines containing gliclazide must undergo RB/BE studies, since there is not enough evidence to recommend the replacement and waiver of such studies for immediate and extended release formulations.

Department of medicine, Educare institute of dental science Malappuram, Kerala and SafeCare clinics, Tirur, Kerala sulfonylureas (SUs) are one of the oldest, time tested and most commonly used oral antidiabetic agent in Type 2 diabetes. Modern SUs like glimepiride and gliclazide XR were preferred over conventional SUs due to its better efficacy and minimal side effects. The use of Modern SUs in the treatment armamentarium of T2DM has evolved, over past few decades. Modern SUs possesses beneficial pancreatic glucose lowering effect and more interestingly extra-pancreatic pleiotropic benefits. This review article discusses on the utility and benefits of SUs beyond glycemic control and explaining on their pleiotropic effects.

Nowadays the diabetes mellitus has epidemic character. That’s why searching and creating of new medicines for effective therapy of this pathology are actual. Phytotherapy is one of the components in the complex treatment of diabetes mellitus type 2. It combines a wide range of pharmacological actions, fewer side effects and toxic reactions on the human body than synthetic drugs. Plants of genus of Portulaca L. can be perspective sources for searching new medicinal plants. Purslane (Portulaca oleracea L.) is used in folk medicine as hypoglycemic agent. The aim of the research was to study the hypoglycemic activity of the infusion of Portulaca oleracea herb. Simulation of insulin resistance was performed with intramuscular injections of glucocorticoids (Dexamethasone, 0.125 mg/kg). Portulaca oleracea infusion administered orally at the dose 10 ml/kg. Gliclazide freshly suspension was used as a reference drug and it was administered orally by 50 mg/kg. Characteristic of glucose homeostasis was carried out using a short insulin test, oral glucose tolerance test. Also assessed the effect of Portulaca oleracea infusion and reference drug on adrenaline hyperglycemia. Glucose level at 30 minutes after administration of insulin in the group that received Portulaca oleracea infusion reduced on 53.9%. There was a decrease on 37.5% in the group of diabetic control, and in the intact group – on 60.2%. The result of oral test of glucose tolerance showed that the area under the glycemic curve in groups that received Portulaca oleracea infusion (314.9 mmol/L·min) and reference drug Gliclazide (376.0 mmol/L·min) did not significantly differ from the similar area of the intact group (372.7 mmol/L·min). The administration of the epinephrine hydrochloride solution caused a sharp and significant increase in the glucose level in the diabetic control group. 90 minutes after the epinephrine injection the glucose level in animals which received Portulaca oleracea infusion increased in 3.15 times, and in the reference-group – in 1.97 times, which significantly differs from the diabetic control group. The obtained results indicate that the infusion of Portulaca oleracea herb reduce the formation of insulin resistance and glucose tolerance in the conditions of experimental dexamethasone diabetes mellitus in rats.

Introduction: Diabetes mellitus is increasing rapidly worldwide, and treatment comes with many challenges. It is estimated that in 2030, approximately 500 million people will live with diabetes across the world—most of which will be type 2 diabetes mellitus (T2DM). Obesity often coincides with T2DM and has been linked to increased insulin resistance, high blood pressure, and high blood lipids. Thus, pharmacological management should be aimed at promoting weight loss or at very least be weight neutral. In many cases the risks of hypoglycaemia and weight gain may delay titration of diabetic agents to HbA1C targets. Both insulin and sulfonylureas are proven medications which are beneficial for tight glycemic control but with an increased risk of weight gain and hypoglycaemia. Newer agents under the drug class glucagon-like peptide receptor antagonists (GLP-1RA) are increasingly being used. Various randomized clinical trials support that obese T2DM patients treated with GLP-1RA lead to better glycaemic control, weight reduction and reduced risk of hypoglycaemia. Case Summary: A 56-year-old female was diagnosed with T2DM in 2003 and had been regularly followed up in diabetes clinic since 2014. During the initial clinic review she had a body weight of 114.9 kg (BMI 40.7), fasting blood glucose was 8 - 9, 2-hour CBG 11-13 and HbA1c of 87. At that time, she was taking insulin glargine (Lantus) 36 units once daily, gliclazide 40 mg in the morning / 120 mg in the evening, metformin slow release 2 g in the evening, and simvastatin 20 mg at bedtime. After discussion with her she was started on the GLP-1RA liraglutide subcutaneously. She had no diabetic related complication. She continued liraglutide since then. Her HbA1c started to improve and also noticed in change in body weight which had gradually decreased from 114.9 to 109 kg. Her liraglutide was held at the latter end of 2018 as her glucose control and weight had been maintained. It was noticed that after stopping liraglutide her blood glucose and weight started to go up again even though her other medications remained same. Her case was discussed at Diabetes MDT and liraglutide1.8mg restarted in September 2019 and since then she able to lose around 5% of her body weight and HBA1C also started to drop. It is noticed that since the starting of her liraglutide her HBA1C level and weight fall by around 1% and 4% respectively. In late 2018 once she stopped liraglutide her HbA1C and weight started to rise again. In 2019 liraglutide was restarted and she managed to reduce body weight by 5kg and HbA1C by 2%. During the whole time period she maintained lifestyle intervention. Discussion: Excessive fat accumulation with potential impairing effects on health know as overweight and obesity, is a major risk factor for type 2 diabetes mellitus. Most T2DM people around 80-90% fall in mild to moderate obesity or overweight need either behaviour or medication-based weight loss programme. In these patients losing as little as 5% of body weight positively affect their cardiovascular mortality and glycemic control. There is no need to mention that losing body weight and maintaining it is a challenge for the majority of diabetic patients and it is especially true for those are on oral hypoglycaemic agents such as insulin, sulfonylurea and thiazolidinediones and insulin. In that case GLP-! Receptor agonists (GLP-1 Ras) is exceptional and it is proven benefit in reducing weight in T2DM obese patients. Liraglutide is first approved in 2010 as an adjunct therapy to diet and exercise for management of type 2 diabetes. Liraglutide is a derivative of GLP-1, a polypeptide incretin hormone secreted by the L-cell of the gastrointestinal tract. It stimulates glucose dependent insulin secretion causing a decrease in plasma glucagon concentrations, delayed gastric emptying, suppress appetite and increased heart rate. It is believed that the weight lowering effect of GLP-1RA is due to appetite suppression and delayed gastric emptying. After liraglutide administration peak absorption occur at 11 hours and its absolute bioavailability is 55%. Its half-life in 13 hours, allowing it once daily administration. It eliminates through liver and kidneys and does not interfere with cytochrome p450 system. Most common side effects are nausea, hypoglycaemia, diarrhoea, constipation, abdominal pain and increased serum lipase. Gastrointestinal intolerance is the most common reason for drug discontinuation in patients. There is also an increased correlation with acute pancreatitis, serious hypoglycaemic episodes, tachycardia, and suicidal behaviour. Liraglutide is contraindicated in pregnancy and should be avoided in nursing mothers, children, and coincident use with other GLP-1 agonists. Five large scale randomized multicenter phase III trials have been conducted to evaluate the efficacy of liraglutide as a weight loss agent. Four of these are part of the Satiety and Clinical Adiposity – Liraglutide evidence in non‐diabetic and diabetic individuals (SCALE) program. During these trails, all participants were encouraged to continue their lifestyle modification. The result of the trail was satisfactory. It was found that mean weight loss was between 6% to 4.7% in comparison to placebo group (2%). A dose dependent weight loss was first observed in LEAD Trials and subsequently in SCALE programme it is confirmed. In a study in Chinese population liraglutide treatment help T2DM patient in weight reduction after 24 weeks of treatment. In long term weight reduction, the 5-year treatment with liraglutide reduce HBA1c level by almost 1%. In various study it confirmed that liraglutide has greater impact on T2DM female gender. In SCALE study it showed that 50% difference in body weight loss between man and women could be due to higher exposure to liraglutide to women. Although exposure was equal in healthy male and female subject. Reference: 1. Randomized control trials for GLP-1Ra 2. Liraglutide for weight management: A critical review of the evidence 3. A review of efficacy and safety data regarding the use of liraglutide, a once-daily human glucagon-like peptide 1 analogue, in the treatment of type 2 diabetes mellitus. 4. Long-Term Effectiveness of Liraglutide for Weight Management and Glycemic Control in Type 2 Diabetes

Objective: The main objective of the present investigation is to develop a sustained-release (SR) formulation to optimize the postprandial elevation of glucose level in type 2 Diabetic subjects using combination therapy. In the present research work, bilayer sustained release formulation of metformin hydrochloride (MFH) and gliclazide (GLZ), based on monolithic-matrix technology was developed and evaluated. Methods: The formulations of metformin hydrochloride layer and gliclazide layer that contain polyox WSR coagulant and different viscosity grades of hydroxyl propyl methylcellulose (HPMC) as sustained-release matrix were prepared by direct compression and wet granulation method respectively. The bilayer tablets were prepared after carrying out the optimization of metformin layer and evaluated for various pre-compression and post-compression parameters. For the best formulation selected on basis of in vitro evaluation of tablets, Fourier-transform infrared spectroscopy (FT-IR) studies and comparison of in vitro dissolution profile of developed formulation with the innovator were performed. Results: Metformin hydrochloride and gliclazide showed sustained release of drug by diffusion mechanism and followed first-order kinetics. The best formulation of metformin hydrochloride (M7) and gliclazide (G8) show 99.93% and 99.65% of drug release in 24 h respectively. The similarity factor (f2) was 79.95 for metformin hydrochloride and 73.62 for gliclazide when compared with the innovator. Conclusion: The monolith diffusion-controlled bilayer tablets of metformin hydrochloride and gliclazide offer improved patient compliance and convenience with better postprandial hyperglycemic control with once-a-day dosing. The sustained release of the drug up to 24 h regulate antidiabetic activity round the clock with minimal side effects.

Abstract BACKGROUND AND AIMS Non-steroidal anti-inflammatory drugs (NSAIDS) have well-understood side effects. Rhabdomyolysis, though, is a rare adverse effect of NSAIDs and only a few cases have been reported. Here, we report a case of NSAID-related acute kidney injury (AKI) in an old diabetic woman who was found to have high muscle enzymes. METHOD A 75-year-old diabetic woman was referred to a nephrology clinic due to nausea, vomiting and high serum creatinine. She was a known case of type 2 diabetes that was well controlled by oral hypoglycemic agents (metformin, gliclazide and linagliptin). The patient was not known to have documented hypertension. She had never visited a nephrologist but her baseline creatinine was 1.2 mg/dL. Her family also admitted that she has frequently used different NSAIDs (celecoxib, diclofenac and ibuprofen) due to knee pain in the past few weeks. The patient had developed lower extremity weakness 3 days before referral followed by nausea and vomiting, 2 days later. Physical examination showed mild pitting edema of both feet. Her new data were as followings: Blood urea nitrogen: 85 mg/dL, creatinine: 7.5 mg/dL, uric acid: 4.5 mg/dL, sodium: 135 meq/L, potassium: 4.7 meq/L, hemoglobin 11.3 g/dL, white blood cells 5400 U/micL, platelets 186 000 U/micL, creatinine phosphokinase (CPK): 12730 U/L, lactate dehydrogenase (LDH) 1344 U/L, alanine transaminase (ALT) 78 U/L and aspartate transaminase (AST) 203 U/L. Urinalysis showed specific gravity 1.020, protein 4+, sugar 1+, blood trace, red blood cells (RBC) 2–4/hpf, white blood cells (WBC) 4–6 per hpf, and also, 2–4 granular casts per hpf were reported. Urine culture result was negative. 24-h urine specimen showed proteinuria of 7300 mg. Renal ultrasound showed normal-sized kidneys with increased corticomedullary differentiation and bilateral simple cortical cysts. Renal cortical thickness was >1 cm bilaterally, and there was no hydronephrosis or other pathologies. Hemodialysis was started for the patient and she underwent a kidney biopsy to define the cause of acute kidney injury (AKI). RESULTS Renal biopsy showed: membranous glomerulonephritis stage 2/4, severe acute tubulointerstitial nephritis, focal global glomerulosclerosis and vascular thickening. Interstitial fibrosis and tubular atrophy (IFTA) were reported to be about 20%. There was no sign of acute tubular necrosis. (pictures). Immunofluorescent (IF) study showed a 1+ granular pattern deposition of IgG along the glomerular basement membrane. CONCLUSION NSAID-related rhabdomyolysis is a rare side effect of this class of analgesics. Although any agent from this class can be causative, most reports involve the most widely used ones: diclofenac and Ibuprofen. AKI in the presented patient could have different etiologies regarding data and medical history. The value of renal biopsy is well depicted in this case. Although rhabdomyolysis seemed to be the principal etiology, at the first sight, NSAID-related interstitial nephritis played the main role in AKI. The patient was put on hemodialysis for 2 weeks. Any forms of NSAIDs were withheld. Acceptable renal recovery was achieved in 3 weeks; the patient was free from dialysis. Two months later, she has creatinine of 1.2 mg/dL and normal CPK and LDH levels. Angiotensin receptor blocker (ARB) was started as the beginning treatment of membranous nephropathy. Renal biopsy is of great value to differentiate causes of non-typical cases of AKI especially in rare cases where laboratory data may be confusing or misleading.

Amorphous ternary solid dispersion has become one of the strategies commonly used for improving the solubility and bioavailability of poorly water soluble drugs. Such multicomponent solid dispersion can be obtained by different techniques, this chapter provides an overview of ternary solid dispersion by co-milling method from the perspectives of physico-chemical characteristics in vitro and in vivo performance. A considerable improvement of solubility was obtained for many active pharmaceutical ingredients (e.g., Ibuprofen, Probucol, Gliclazid, Fenofibrate, Ibrutinib and Naproxen) and this was correlated to the synergy of multiple factors (hydrophilicity enhancement, particle size reduction, drug-carrier interactions, anti-plasticizing effect and complexation efficiency). This enhanced pharmacokinetic properties and bioavailability of these drug molecules (1.49 to 15-folds increase in plasma drug concentration). A particular focus was accorded to compare the ternary and binary system including Ibuprofen and highlighting the contribution of thermal and spectral characterization techniques. The addition of polyvinylpyrrolidone (PVP K30), a low molecular weight molecule, into the binary solid dispersion (Ibuprofen/β-cyclodextrin), leads to a 1.5–2 folds increase in the drug intrinsic dissolution rate only after 10 min. This resulted from physical stabilization of amorphous Ibuprofen by reducing its molecular mobility and inhibiting its recristallization even under stress conditions (75% RH and T = 40°C for six months).