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  1. Al Saleh Y, Al Busaidi N, Al Dahi W, Almajnoni M, Mohammed AS, Alshali K, et al.
    Adv Ther, 2023 Jul;40(7):2965-2984.
    PMID: 37233878 DOI: 10.1007/s12325-023-02529-7
    Type 2 diabetes mellitus (T2DM) and hypertension are leading risk factors for death and disability in the Middle East. Both conditions are highly prevalent, underdiagnosed and poorly controlled, highlighting an urgent need for a roadmap to overcome the barriers to optimal glycaemic and blood pressure management in this region. This review provides a summary of the Evidence in Diabetes and Hypertension Summit (EVIDENT) held in September 2022, which discussed current treatment guidelines, unmet clinical needs and strategies to improve treatment outcomes for patients with T2DM and hypertension in the Middle East. Current clinical guidelines recommend strict glycaemic and blood pressure targets, presenting several treatment options to achieve and maintain these targets and prevent complications. However, treatment targets are infrequently met in the Middle East, largely due to high clinical inertia among physicians and low medication adherence among patients. To address these challenges, clinical guidelines now provide individualised therapy recommendations based on drug profiles, patient preferences and management priorities. Efforts to improve the early detection of prediabetes, T2DM screening and intensive, early glucose control will minimise long-term complications. Physicians can use the T2DM Oral Agents Fact Checking programme to help navigate the wide range of treatment options and guide clinical decision-making. Sulfonylurea agents have been used successfully to manage T2DM; a newer agent, gliclazide MR (modified release formulation), has the advantages of a lower incidence of hypoglycaemia with no risk of cardiovascular events, weight neutrality and proven renal benefits. For patients with hypertension, single-pill combinations have been developed to improve efficacy and reduce treatment burden. In conjunction with pragmatic treatment algorithms and personalised therapies, greater investments in disease prevention, public awareness, training of healthcare providers, patient education, government policies and research are needed to improve the quality of care of patients with T2DM and/or hypertension in the Middle East.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
  2. Butt MD, Ong SC, Rafiq A, Malik T, Sajjad A, Batool N, et al.
    Sci Rep, 2023 Dec 27;13(1):23037.
    PMID: 38155289 DOI: 10.1038/s41598-023-50517-2
    In 2021, the International Diabetes Federation (IDF) reported that the prevalence of diabetes in Pakistan was 9.6%, higher than the global average. However, adherence to treatment guidelines, e.g., American Diabetes Association and Pakistan Endocrine Society and prescription patterns for Oral anti-diabetes (OAD), is poorly understood in Pakistan. Therefore, this study aimed to examine the prescribing practices of anti-diabetic medications, an association of lifestyle modification with drugs prescribed, and their effectiveness in preserving ideal glycemic levels in diabetic patients undergoing treatment in tertiary care teaching hospitals in rural and urban Pakistan. In this cross-sectional study, data were collected from prescriptions of outpatient diabetic patients from different rural and urban tertiary care hospitals between October 2021 and February 2022. 388 participants were enrolled in the study for a detailed interview on prescription evaluation and glycemic control. The coinvestigators conducted an interview with the patient and used a pre-validated questionnaire to collect the data. The relationship between following treatment guidelines and clinical and demographic factors was found using chi-square tests for bivariate analyses. The study reported that out of 388, the mean ages of the patients were 48 ± 12.4, and the majority were female. It was observed that 60.1% and 66.5% have uncontrolled fasting and random blood glucose, respectively. The education level of the study participants was also below par to have a complete understanding of the medical condition and self-management therapy. Even though they were taking the right medications-an average prescription regimen included 5.08 medications-52.1% of the studied people had glycated haemoglobin (HbA1c) levels higher than the therapeutic threshold set by the International Diabetes Federation. In this modern era, it was observed that the prescribing trend was still focused on traditional therapeutic options Biguanides, sulfonylureas, and dipeptidyl peptidase-4 inhibitors were prescribed in 64.6% of the patients. A significant association was found between glycemic control and body mass index, adherence to lifestyle modifications, and the number of medications prescribed (p-value 
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
  3. Colagiuri S, Matthews D, Leiter LA, Chan SP, Sesti G, Marre M
    Diabetes Res Clin Pract, 2018 Sep;143:1-14.
    PMID: 29802958 DOI: 10.1016/j.diabres.2018.05.028
    The sulfonylureas are effective oral glucose-lowering agents with a long history of clinical use. While all have the same general mechanism of action, their pharmacokinetic properties are influenced by factors such as dosage, rate of absorption, duration of action, route of elimination, tissue specificity, and binding affinity for pancreatic β-cell receptor. The result is a class of agents with similar HbA1c-lowering efficacy, but well-documented differences in terms of effects on hypoglycemia, and cardiovascular and renal safety. This review examines the differences between currently available sulfonylureas with a focus on how gliclazide modified release (MR) differs from other members of this class and from newer oral antihyperglycemic agents in the form of dipeptidyl peptidase-4 (DPP4) and sodium- glucose cotransporter 2 (SGLT2) inhibitors. The first part focuses on major outcome trials that have been conducted with the sulfonylureas and new oral agents. Consideration is then given to factors important for day-to-day prescribing including efficacy and durability, weight changes, hypoglycemia, renal effects and cost. Based on current evidence, third-generation sulfonylureas such as gliclazide MR possess many of the properties desired of a type 2 diabetes drug including high glucose-lowering efficacy, once-daily oral administration, few side effects other than mild hypoglycemia, and cardiovascular safety.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
  4. Aravind SR, Al Tayeb K, Ismail SB, Shehadeh N, Kaddaha G, Liu R, et al.
    Curr Med Res Opin, 2011 Jun;27(6):1237-42.
    PMID: 21506631 DOI: 10.1185/03007995.2011.578245
    To determine the incidence of hypoglycaemia during Ramadan in Muslim subjects with type 2 diabetes treated with a sulphonylurea.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use*
  5. Chan SP, Ji LN, Nitiyanant W, Baik SH, Sheu WH
    Diabetes Res Clin Pract, 2010 Aug;89(2):e30-2.
    PMID: 20541826 DOI: 10.1016/j.diabres.2010.05.008
    Symptoms of hypoglycemia were reported by 35.8% of patients with type 2 diabetes treated with oral antihyperglycemic agents in the Asia-Pacific region. Symptoms were severe in 11.6% and very severe in 8.2% of patients experiencing hypoglycemia.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
  6. Lim P, Khoo OT
    Singapore Med J, 1971 Dec;12(6):319-22.
    PMID: 5141589
    A clinical study was undertaken of new diabetics seen at a general medical unit in Singapore. Over a period of 12 months, there were seventy-five cases of which 38 (50.7%) were Chinese, 15 (20%) Malays and 22 (29.3%) Indians. Male patients were twice as common as female patients. The majority of patients (61.3%) were in the 5th and 6th decade and only 23 (30.7%) were obese. Oral sulphonylurea and dieting provided effective control in 80.6% of the patients, and only 9% of patients required insulin. Ketosis was present in only 6 cases and was easily controlled with appropriate treatment. Other clinical features are presented and discussed.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
  7. Anwar A, Azmi KN, Hamidon BB, Khalid BA
    Med J Malaysia, 2006 Mar;61(1):28-35.
    PMID: 16708731 MyJurnal
    This study was conducted to compare the treatment efficacy between a prandial glucose regulator, repaglinide and a new sulphonylurea, glimepiride in Muslim Type 2 diabetic patients who practice Ramadan fasting. Forty-one patients, previously treated with a sulphonylurea or metformin, were divided to receive either repaglinide (n=20, preprandially three-times daily) or glimepiride (n=21, preprandially once daily) 3 months before the month of Ramadan. During Ramadan, patients modified their eating pattern to two meals daily, and the triple doses of repaglinide were redistributed to two preprandial doses. Four point blood glucose monitoring were performed weekly during the month of Ramadan and the subsequent month. Measurements of the 4-point blood glucose were significantly lower in the glimepiride group compared to the repaglinide group both during and after Ramadan. The glycaemic excursion was better in the morning for the repaglinide group and better in the afternoon and evening for the glimepiride group during the Ramadan period. There was no statistically significant difference in the incidence of hypoglycaemia between the two groups during and after Ramadan. There was no difference in the glycaemic excursion post-Ramadan. The longer duration of action of glimepiride may offer an advantage over repaglinide during the 13.5 hours of fast in Ramadan for diabetic patients.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use*
  8. Loganadan NK, Huri HZ, Vethakkan SR, Hussein Z
    Pharmacogenomics, 2020 06;21(9):587-600.
    PMID: 32468916 DOI: 10.2217/pgs-2019-0171
    Background: Due to several limitations in the study designs of sulfonylurea pharmacogenomics studies, we investigated the clinical and genetic predictors of secondary sulfonylurea failure in Type 2 diabetes patients. Materials & methods: Patients receiving the maximum sulfonylurea and metformin doses for >1 year were enrolled. Secondary sulfonylurea failure was defined as HbA1c >7.0% (>53 mmol/mol) after a 12-month follow-up. Results: By multivariate analysis, increased insulin resistance (HOMA2-IR), baseline HbA1c >7.0%, residing in eastern Peninsular Malaysia, and the CC genotype of rs757110 ABCC8 gene polymorphism were independent predictors of secondary sulfonylurea failure (p sulfonylurea-induced hypoglycemia was protective against such failure (p Sulfonylurea does not benefit patients with an increased risk of secondary sulfonylurea failure.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use*
  9. Ooi HL, Wu LL
    Singapore Med J, 2012 Jul;53(7):e142-4.
    PMID: 22815030
    Neonatal diabetes mellitus (DM) is defined as insulin-requiring DM in the first six months of life. Unlike type 1 DM, it is a monogenic disorder resulting from a de novo mutation in the genes involved in the development of the pancreas, β-cell mass or secretory function. The majority of neonatal DM cases are caused by a heterozygous activating mutation in the KCNJ11 or ABCC8 genes that encode the Kir6.2 and SUR1 protein subunits, respectively, in the KATP channel. Sulphonylurea, a KATP channel inhibitor, can restore insulin secretion, hence offering an attractive alternative to insulin therapy. We report three cases of neonatal DM and their genetic mutations. Two patients were successfully switched over to sulphonylurea monotherapy with resultant improvement in the quality of life and a more stable blood glucose profile. Patients with neonatal DM should undergo genetic evaluation. For patients with KCNJ11 and ABCC8 gene mutation, oral sulphonylurea should be considered.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
  10. Aravind SR, Ismail SB, Balamurugan R, Gupta JB, Wadhwa T, Loh SM, et al.
    Curr Med Res Opin, 2012 Aug;28(8):1289-96.
    PMID: 22738801 DOI: 10.1185/03007995.2012.707119
    To compare the incidence of symptomatic hypoglycemia between sitagliptin and sulfonylurea in Muslim patients with type 2 diabetes who fasted during Ramadan.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
  11. Loh HH, Yee A, Loh HS, Sukor N, Kamaruddin NA
    Prim Care Diabetes, 2016 Jun;10(3):210-9.
    PMID: 26392074 DOI: 10.1016/j.pcd.2015.09.001
    AIM: To systematically review the literature to compare the use of DPP4 inhibitors vs sulphonylurea in type 2 diabetic Muslim patients who fast in Ramadan, with regards to its safety, tolerability, glycemic control, and body weight changes.

    METHODS: All English-language medical literature published from inception till October 2014 which met the inclusion criteria were reviewed and analyzed.

    RESULTS: A total of nine papers were included, reviewed and analyzed. The total sample size was 4276 patients. All studies used either of the two DPP4 inhibitors - Vildagliptin or Sitagliptin, vs sulphonylurea or meglitinides. Patients receiving DPP4 inhibitors were less likely to develop symptomatic hypoglycemia (risk ratio 0.46; 95% CI, 0.30-0.70), confirmed hypoglycemia (risk ratio 0.36; 95% CI, 0.21-0.64) and severe hypoglycemia (risk ratio 0.22; 95% CI, 0.10-0.53) compared with patients on sulphonylureas. There was no statistically significant difference in HbA1C changes comparing Vildagliptin and sulphonylurea.

    CONCLUSION: DPP4 inhibitor is a safer alternative to sulphonylurea in Muslim patients with type 2 diabetes mellitus who fast during the month of Ramadan as it is associated with lower risk of symptomatic, confirmed and severe hypoglycemia, with efficacy comparable to sulphonylurea.

    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use*
  12. Chan SP, Colagiuri S
    Diabetes Res Clin Pract, 2015 Oct;110(1):75-81.
    PMID: 26361859 DOI: 10.1016/j.diabres.2015.07.002
    AIMS: Sulfonylureas are well positioned in treating type 2 diabetes, after lifestyle modification and metformin. The sulfonylurea gliclazide was given preference over glibenclamide in older people with type 2 diabetes in the World Health Organization model list of essential medicines. Consequently, a systematic review and meta-analysis of randomized controlled trials of the efficacy and safety of gliclazide versus other oral insulinotropic agents (sulfonylureas, dipeptidyl peptidase-4 inhibitors, and glinides) was performed.

    METHODS: Two reviewers searched MEDLINE for studies of ≥12 weeks duration in adults with type 2 diabetes. The key search word was "gliclazide", filtered with "randomized controlled trial", "human" and "19+ years". Differences were explored in mean change in glycated hemoglobin (HbA(1c)) from baseline (primary outcome) and risk of hypoglycemia (secondary outcome) between gliclazide and other oral insulinotropic agents; and other sulfonylureas.

    RESULTS: Nine out of 181 references reported primary outcomes, of which 7 reported secondary outcomes. Gliclazide lowered HbA1c more than other oral insulinotropic agents, with a weighted mean difference of -0.11% (95%, CI -0.19 to -0.03%, P=0.008, I(2)=60%), though not more than other sulfonylureas (-0.12%; 95%, CI -0.25 to 0.01%, P=0.07, I(2)=77%). Risk of hypoglycemia with gliclazide was not different to other insulinotropic agents (RR 0.85; 95%, CI 0.66 to 1.09, P=0.20, I(2)=61%) but significantly lower than other sulfonylureas (RR 0.47; 95%, CI 0.27 to 0.79, P=0.004, I(2)=0%).

    CONCLUSION: Compared with other oral insulinotropic agents, gliclazide significantly reduced HbA1c with no difference regarding hypoglycemia risk. Compared with other sulfonylureas, HbA1c reduction with gliclazide was not significantly different, but hypoglycemia risk was significantly lower.

    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
  13. Loganadan NK, Huri HZ, Vethakkan SR, Hussein Z
    Pharmacogenomics J, 2016 06;16(3):209-19.
    PMID: 26810132 DOI: 10.1038/tpj.2015.95
    The clinical response to sulphonylurea, an oral antidiabetic agent often used in combination with metformin to control blood glucose in type 2 diabetes (T2DM) patients, has been widely associated with a number of gene polymorphisms, particularly those involved in insulin release. We have reviewed the genetic markers of CYP2C9, ABCC8, KCNJ11, TCF7L2 (transcription factor 7-like 2), IRS-1 (insulin receptor substrate-1), CDKAL1, CDKN2A/2B, KCNQ1 and NOS1AP (nitric oxide synthase 1 adaptor protein) genes that predict treatment outcomes of sulphonylurea therapy. A convincing pattern for poor sulphonylurea response was observed in Caucasian T2DM patients with rs7903146 and rs1801278 polymorphisms of the TCF7L2 and IRS-1 genes, respectively. However, limitations in evaluating the available studies including dissimilarities in study design, definitions of clinical end points, sample sizes and types and doses of sulphonylureas used as well as ethnic variability make the clinical applications challenging. Future studies need to address these limitations to develop personalized sulphonylurea medicine for T2DM management.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use*
  14. Yu Pan C, Han P, Liu X, Yan S, Feng P, Zhou Z, et al.
    Diabetes Metab Res Rev, 2014 Nov;30(8):726-35.
    PMID: 24639432 DOI: 10.1002/dmrr.2541
    BACKGROUND: This study assessed the efficacy and safety of the once-daily glucagon-like peptide-1 receptor agonist, lixisenatide, in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin ± sulfonylurea.
    METHODS: In this 24-week, double-blind, placebo-controlled, multinational study, patients were randomized to lixisenatide 20 µg once daily or placebo. The primary endpoint was absolute change in glycated haemoglobin (HbA1c ) from baseline to week 24.
    RESULTS: A total of 391 patients were randomized. Lixisenatide significantly reduced HbA1c levels compared with placebo (LS mean difference: -0.36%, p = 0.0004). A significantly higher proportion of lixisenatide-treated patients achieved HbA1c targets of <7% (p = 0.003) and ≤6.5% (p = 0.001) versus placebo. Lixisenatide was associated with a statistically significant reduction in 2-h postprandial plasma glucose after a standardized breakfast versus placebo (LS mean difference: -4.28 mmol/L, p sulfonylurea, lixisenatide significantly improved glycaemic control and was well tolerated during the 24-week study.
    TRIAL REGISTRATION: ClinicalTrials.gov NCT01169779.
    KEYWORDS: Asia; glucagon-like peptide-1 (GLP-1) receptor agonists; lixisenatide; type 2 diabetes mellitus (T2DM)
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
  15. Liu S, Liu JJ, Gurung RL, Chan C, Yeo D, Ang K, et al.
    Ann Acad Med Singap, 2019 Jul;48(7):217-223.
    PMID: 31495867
    INTRODUCTION: The risk for diabetes progression varies greatly in individuals with type 2 diabetes mellitus (T2DM). We aimed to study the clinical determinants of diabetes progression in multiethnic Asians with T2DM.

    MATERIALS AND METHODS: A total of 2057 outpatients with T2DM from a secondary-level Singapore hospital were recruited for the study. Diabetes progression was defined as transition from non-insulin use to requiring sustained insulin treatment or glycated haemoglobin (HbA1c) ≥8.5% when treated with 2 or more oral hypoglycaemic medications. Multivariable logistic regression (LR) was used to study the clinical and biochemical variables that were independently associated with diabetes progression. Forward LR was then used to select variables for a parsimonious model.

    RESULTS: A total of 940 participants with no insulin use or indication for insulin treatment were analysed. In 3.2 ± 0.4 (mean ± SD) years' follow-up, 163 (17%) participants experienced diabetes progression. Multivariable LR revealed that age at T2DM diagnosis (odds ratio [95% confidence interval], 0.96 [0.94-0.98]), Malay ethnicity (1.94 [1.19-3.19]), baseline HbA1c (2.22 [1.80-2.72]), body mass index (0.96 [0.92-1.00]) and number of oral glucose-lowering medications (1.87 [1.39-2.51]) were independently associated with diabetes progression. Area under receiver operating characteristic curve of the parsimonious model selected by forward LR (age at T2DM diagnosis, Malay ethnicity, HbA1c and number of glucose-lowering medication) was 0.76 (95% CI, 0.72-0.80).

    CONCLUSION: Young age at T2DM diagnosis, high baseline HbA1c and Malay ethnicity are independent determinants of diabetes progression in Asians with T2DM. Further mechanistic studies are needed to elucidate the pathophysiology underpinning progressive loss of glycaemic control in patients with T2DM.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use*
  16. Ji L, Han P, Liu Y, Yang G, Dieu Van NK, Vijapurkar U, et al.
    Diabetes Obes Metab, 2015 Jan;17(1):23-31.
    PMID: 25175734 DOI: 10.1111/dom.12385
    To evaluate the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in Asian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin or metformin in combination with sulphonylurea.
    Matched MeSH terms: Sulfonylurea Compounds/therapeutic use
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