Displaying publications 1 - 20 of 22 in total

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  1. Kongwatcharapong J, Dilokthornsakul P, Nathisuwan S, Phrommintikul A, Chaiyakunapruk N
    Int J Cardiol, 2016 May 15;211:88-95.
    PMID: 26991555 DOI: 10.1016/j.ijcard.2016.02.146
    Recent studies have suggested that dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) may be associated with increased risk of heart failure (HF), but evidence was inconclusive. We aimed to determine the effects of DPP-4 inhibitors on risk of HF.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors
  2. A/L B Vasanth Rao VR, Tan SH, Candasamy M, Bhattamisra SK
    Diabetes Metab Syndr, 2018 11 30;13(1):754-762.
    PMID: 30641802 DOI: 10.1016/j.dsx.2018.11.054
    Diabetic nephropathy (DN) is a major cause of end-stage renal disease and affects a large number of individuals with diabetes. However, the development of specific treatments for DN has not yet been identified. Hence, this review is concisely designed to understand the molecular pathways leading to DN in order to develop suitable therapeutic strategies. Extensive literature search have been carried in regard with the pathogenesis and pathophysiology of DN, drug targets and updates on clinical trials, the consequences associated with DN and the potential biomarkers for diagnosis and prediction of DN are discussed in this review. DN is characterised by microalbuminuria and macroalbuminuria, and morphological changes such as glomerular thickening, interstitial fibrosis, formation of nodular glomerulosclerosis and decreased endothelial cell fenestration. Besides, the involvement of renin-angiotensin-aldosterone system, inflammation and genetic factors are the key pathways in the progression of DN. In regard with drug development drugs targeted to epidermal growth factor, inflammatory cytokines, ACTH receptor and TGFβ1 receptors are in pipeline for clinical trials whereas, several drugs have also failed in phase III and phase IV of clinical trials due to lack of efficacy and severe adverse effect. The research on DN is limited with respect to its pathogenesis and drug development. Thus, a more detailed understanding of the pathogenesis of DN is very essential to progress in the drug development process.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/pharmacology; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
  3. Al-Fakih AM, Algamal ZY, Lee MH, Aziz M, Ali HTM
    SAR QSAR Environ Res, 2019 Jun;30(6):403-416.
    PMID: 31122062 DOI: 10.1080/1062936X.2019.1607899
    Time-varying binary gravitational search algorithm (TVBGSA) is proposed for predicting antidiabetic activity of 134 dipeptidyl peptidase-IV (DPP-IV) inhibitors. To improve the performance of the binary gravitational search algorithm (BGSA) method, we propose a dynamic time-varying transfer function. A new control parameter,
    μ
    , is added in the original transfer function as a time-varying variable. The TVBGSA-based model was internally and externally validated based on

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    , Y-randomization test, and applicability domain evaluation. The validation results indicate that the proposed TVBGSA model is robust and not due to chance correlation. The descriptor selection and prediction performance of TVBGSA outperform BGSA method. TVBGSA shows higher

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    compared to obtained results by BGSA, indicating the best prediction performance of the proposed TVBGSA model. The results clearly reveal that the proposed TVBGSA method is useful for constructing reliable and robust QSARs for predicting antidiabetic activity of DPP-IV inhibitors prior to designing and experimental synthesizing of new DPP-IV inhibitors.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/chemistry*
  4. Chong SC, Sukor N, Robert SA, Ng KF, Kamaruddin NA
    Front Endocrinol (Lausanne), 2022;13:1012412.
    PMID: 36267570 DOI: 10.3389/fendo.2022.1012412
    BACKGROUND: In contrast to Western population, glucagon-like peptide-1 (GLP-1) levels are preserved in some East Asian population with type 2 diabetes (T2D), explaining why dipeptidyl peptidase-IV (DPP-IV) inhibitors are more effective in East Asians. We assessed whether differences in endogenous GLP-1 levels resulted in different treatment responses to DPP-IV inhibitors in prediabetes and T2D.

    METHODS: A prospective 12-week study using linagliptin 5mg once daily in 50 subjects (28 prediabetes and 22 T2D) who were stratified into high versus low fasting GLP-1 groups. A 75-g oral glucose tolerance test (OGTT) was performed at week 0 and 12. Primary outcomes were changes in HbA1c, fasting and post-OGTT glucose after 12 weeks. Secondary outcomes included changes in insulin resistance and beta cell function indices.

    RESULTS: There was a greater HbA1c reduction in subjects with high GLP-1 compared to low GLP-1 levels in both the prediabetes and T2D populations [least-squares mean (LS-mean) change of -0.33% vs. -0.11% and -1.48% vs. -0.90% respectively)]. Linagliptin significantly reduced glucose excursion by 18% in high GLP-1 compared with 8% in low GLP-1 prediabetes groups. The reduction in glucose excursion was greater in high GLP-1 compared to low GLP-1 T2D by 30% and 21% respectively. There were significant LS-mean between-group differences in fasting glucose (-0.95 mmol/L), 2-hour glucose post-OGTT (-2.4 mmol/L) in the high GLP-1 T2D group. Improvement in insulin resistance indices were seen in the high GLP-1 T2D group while high GLP-1 prediabetes group demonstrated improvement in beta cell function indices. No incidence of hypoglycemia was reported.

    CONCLUSIONS: Linagliptin resulted in a greater HbA1c reduction in the high GLP-1 prediabetes and T2D compared to low GLP-1 groups. Endogenous GLP-1 level play an important role in determining the efficacy of DPP-IV inhibitors irrespective of the abnormal glucose tolerance states.

    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors*
  5. Balakumar P, Dhanaraj SA
    Cell Signal, 2013 Sep;25(9):1799-803.
    PMID: 23707531 DOI: 10.1016/j.cellsig.2013.05.009
    Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/pharmacology; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use*
  6. Permsuwan U, Dilokthornsakul P, Thavorn K, Saokaew S, Chaiyakunapruk N
    J Med Econ, 2017 Feb;20(2):171-181.
    PMID: 27645706 DOI: 10.1080/13696998.2016.1238386
    OBJECTIVE: With a high prevalence of chronic kidney disease (CKD) in type 2 diabetes (T2DM) in Thailand, the appropriate treatment for the patients has become a major concern. This study aimed to evaluate long-term cost-effective of dipeptidyl peptidase-4 (DPP-4) inhibitor monothearpy vs sulfonylurea (SFU) monotherapy in people with T2DM and CKD.

    METHODS: A validated IMS CORE Diabetes Model was used to estimate the long-term costs and outcomes. The efficacy parameters were identified and synthesized using a systematic review and meta-analysis. Baseline characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. Costs were expressed in 2014 US Dollars. Outcomes were presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty.

    RESULTS: From a societal perspective, treatment with DPP-4 inhibitors yielded more quality-adjusted life years (QALYs) (0.024) at a higher cost (>66,000 Thai baht (THB) or >1,829.27 USD) per person than SFU, resulting in the ICER of >2.7 million THB/QALY (>74,833.70 USD/QALY). The cost-effectiveness results were mainly driven by differences in HbA1c reduction, hypoglycemic events, and drug acquisition cost of DPP-4 inhibitors. At the ceiling ratio of 160,000 THB/QALY (4,434.59 USD/QALY), the probability that DPP-4 inhibitors are cost-effective compared to SFU was less than 10%.

    CONCLUSIONS: Compared to SFU, DPP-4 inhibitor monotherapy is not a cost-effective treatment for people with T2DM and CKD in Thailand.

    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/administration & dosage; Dipeptidyl-Peptidase IV Inhibitors/economics*
  7. Zabidi NA, Ishak NA, Hamid M, Ashari SE, Mohammad Latif MA
    J Enzyme Inhib Med Chem, 2021 Dec;36(1):109-121.
    PMID: 33249946 DOI: 10.1080/14756366.2020.1844680
    The inhibition of α-glucosidase and DPP enzymes capable of effectively reducing blood glucose level in the management of type 2 diabetes. The purpose of the present study is to evaluate the inhibitory potential of α-glucosidase and DPP (IV) activity including with the 2-NBDG uptake assay and insulin secretion activities through in vitro studies. The selected of active compounds obtained from the screening of compounds by LC-MS were docked with the targeted enzyme that involved in the mechanism of T2DM. From the results, root extracts displayed a better promising outcome in α-glucosidase (IC50 2.72 ± 0.32) as compared with the fruit extracts (IC50 3.87 ± 0.32). Besides, root extracts also displayed a better activity in the inhibition of DPP (IV), enhance insulin secretion and glucose uptake activity. Molecular docking results revealing that phlorizin binds strongly with α-glucosidase, DPP (IV) and Insulin receptor (IR) enzymes with achieving the lowest binding energy value. The present work suggests several of the compounds have the potential that contribute towards inhibiting α-glucosidase and DPP (IV) and thus effective in lowering post-prandial hyperglycaemia.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/isolation & purification; Dipeptidyl-Peptidase IV Inhibitors/pharmacology*; Dipeptidyl-Peptidase IV Inhibitors/chemistry
  8. Mudgil P, Kamal H, Priya Kilari B, Mohd Salim MAS, Gan CY, Maqsood S
    Food Chem, 2021 Aug 15;353:129374.
    PMID: 33740505 DOI: 10.1016/j.foodchem.2021.129374
    Camel milk proteins are an important substrate for bioactive peptides generation. This study investigates in-vitro antidiabetic effect (via inhibition of α-amylase (AA), α-glucosidase (AG) and dipeptidyl peptidase IV (DPP-IV)) of bovine (BC) and camel casein (CC) hydrolysates. Further, effect of simulated gastrointestinal digestion (SGID) on inhibitory potential of generated hydrolysates was also explored. Both BC and CC hydrolysates displayed potent inhibitory properties against AA (IC50 value- 0.58 & 0.59 mg/mL), AG (IC50 value- 1.04 & 0.59 mg/mL) and DPP-IV (IC50 value- 0.62 & 0.66 mg/mL), respectively. Among different peptides identified in BC and CC hydrolysates, it was observed that FLWPEYGAL was predicted to be most potent inhibitory peptide against AA. While LPTGWLM, MFE and GPAHCLL as most active inhibitor of AG and HLPGRG, QNVLPLH and PLMLP were predicted to be active against DPP-IV. Overall, BC and CC hydrolysates can be proposed to be used in different food formulations as functional antidiabetic agents.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/pharmacology
  9. 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: Dipeptidyl-Peptidase IV Inhibitors/adverse effects; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use*
  10. Hasan SS, Kow CS, Bain A, Kavanagh S, Merchant HA, Hadi MA
    Expert Opin Pharmacother, 2021 Feb;22(2):229-240.
    PMID: 33054481 DOI: 10.1080/14656566.2020.1837114
    INTRODUCTION: Diabetes mellitus is one of the most prevalent comorbidities identified in patients with coronavirus disease 2019 (COVID-19). This article aims to discuss the pharmacotherapeutic considerations for the management of diabetes in hospitalized patients with COVID-19.

    AREAS COVERED: We discussed various aspects of pharmacotherapeutic management in hospitalized patients with COVID-19: (i) susceptibility and severity of COVID-19 among individuals with diabetes, (ii) glycemic goals for hospitalized patients with COVID-19 and concurrent diabetes, (iii) pharmacological treatment considerations for hospitalized patients with COVID-19 and concurrent diabetes.

    EXPERT OPINION: The glycemic goals in patients with COVID-19 and concurrent type 1 (T1DM) or type 2 diabetes (T2DM) are to avoid disruption of stable metabolic state, maintain optimal glycemic control, and prevent adverse glycemic events. Patients with T1DM require insulin therapy at all times to prevent ketosis. The management strategies for patients with T2DM include temporary discontinuation of certain oral antidiabetic agents and consideration for insulin therapy. Patients with T2DM who are relatively stable and able to eat regularly may continue with oral antidiabetic agents if glycemic control is satisfactory. Hyperglycemia may develop in patients with systemic corticosteroid treatment and should be managed upon accordingly.

    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/adverse effects; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
  11. Jamaluddin JL, Huri HZ, Vethakkan SR, Mustafa N
    Pharmacogenomics, 2014 Feb;15(2):235-49.
    PMID: 24444412 DOI: 10.2217/pgs.13.234
    In the adult pancreas, the expression of the genes PAX4, KCNQ1, TCF7L2, KCNJ11, ABCC8, MTNR1B and WFS1 are mainly restricted to β cells to maintain glucose homeostasis. We have identified these genes as the main regulators of incretin-mediated actions, and therefore they may potentially influence the response of DPP-4 inhibitors. This review represents the first detailed exploration of pancreatic β-cell genes and their variant mechanisms, which could potentially affect the response of DPP-4 inhibitors in Type 2 diabetes. We have focused on the signaling pathways of these genes to understand their roles in gastrointestinal incretin-mediated effects; and finally, we sought to associate gene mechanisms with their Type 2 diabetes risk variants to predict the responses of DPP-4 inhibitors for this disease.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/administration & dosage*
  12. Jamaluddin JL, Huri HZ, Vethakkan SR
    Pharmacogenomics, 2016 06;17(8):867-81.
    PMID: 27249660 DOI: 10.2217/pgs-2016-0010
    AIM: To determine the clinical and genetic predictors of the dipeptidyl peptidase-4 (DPP-4) inhibitor treatment response in Type 2 diabetes mellitus (T2DM) patients.

    PATIENTS & METHODS: DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitagliptin, vildagliptin or linagliptin. Genotyping was performed by Applied Biosystems TaqMan SNP genotyping assay.

    RESULTS: Patients with triglyceride levels less than 1.7 mmol/l (odds ratio [OR]: 2.2.; 95% CI: 1.031-4.723), diastolic blood pressure (DBP) less than 90 mmHg (OR: 1.7; 95% CI: 1.009-2.892) and KCNJ11 rs2285676 (genotype CC) (OR: 2.0; 95% CI: 1.025-3.767) were more likely to response to DPP-4 inhibitor treatment compared with other patients, as measured by HbA1c levels.

    CONCLUSION: Triglycerides, DBP and KCNJ11 rs2285676 are predictors of the DPP-4 inhibitor treatment response in T2DM patients.

    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/therapeutic use*
  13. Lee SW, Lee JY, Tan CS, Wong CP
    Medicine (Baltimore), 2016 Jan;95(2):e2457.
    PMID: 26765440 DOI: 10.1097/MD.0000000000002457
    Ramadan is the holy month for Muslims whereby they fast from predawn to after sunset and is observed by all healthy Muslim adults as well as a large population of type 2 diabetic Muslims.To determine the comparative effectiveness of various strategies that have been used for type 2 diabetic Muslim who fast during Ramadan.A systematic review and network meta-analysis of randomized controlled studies (RCT) as well as observational studies for patients with type 2 diabetes who fasted during Ramadan was conducted. Eight databases were searched from January 1980 through October 2015 for relevant studies. Two reviewers independently screened and assessed study for eligibility, assessed the risk of bias, and extracted relevant data. A network meta-analysis for each outcome was fitted separately, combining direct and indirect evidence for each comparison.Twenty-nine studies, 16 RCTs and 13 observational studies each met the inclusion criteria. The most common strategy used was drug changes during the Ramadan period, which found that the use of DPP-4 (Dipeptidyl peptidase inhibitor -4) inhibitors were associated with a reduction in incidence of experiencing hypoglycemia during Ramadan in both RCTs (pooled relative risk: 0.56; 95% confidence interval: 0.44-0.72) as well as in observational studies (pooled relative risk: 0.27; 0.09-0.75). Ramadan-focused education was shown to be beneficial in reducing hypoglycemia in observational studies but not RCTs (0.25 versus 1.00). Network meta-analyses suggest that incretin mimetics can reduce the risk of hypoglycemia by nearly 1.5 times.The newer antidiabetic agents appear to lower the risk of hypoglycemia and improved glycemic control when compared with sulfonylureas. Ramadan-focused education shows to be a promising strategy but more rigorous examination from RCTs are required.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/administration & dosage*
  14. Ashraf A, Mudgil P, Palakkott A, Iratni R, Gan CY, Maqsood S, et al.
    J Dairy Sci, 2021 Jan;104(1):61-77.
    PMID: 33162074 DOI: 10.3168/jds.2020-18627
    The molecular basis of the anti-diabetic properties of camel milk reported in many studies and the exact active agent are still elusive. Recent studies have reported effects of camel whey proteins (CWP) and their hydrolysates (CWPH) on the activities of dipeptidyl peptidase IV (DPP-IV) and the human insulin receptor (hIR). In this study, CWPH were generated, screened for DPP-IV binding in silico and inhibitory activity in vitro, and processed for peptide identification. Furthermore, pharmacological action of intact CWP and their selected hydrolysates on hIR activity and signaling and on glucose uptake were investigated in cell lines. Results showed inhibition of DPP-IV by CWP and CWPH and their positive action on hIR activation and glucose uptake. Interestingly, the combination of CWP or CWPH with insulin revealed a positive allosteric modulation of hIR that was drastically reduced by the competitive hIR antagonist. Our data reveal for the first time the profiling and pharmacological actions of CWP and their derived peptides fractions on hIR and their pathways involved in glucose homeostasis. This sheds more light on the anti-diabetic properties of camel milk by providing the molecular basis for the potential use of camel milk in the management of diabetes.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/pharmacology
  15. Quek A, Kassim NK, Lim PC, Tan DC, Mohammad Latif MA, Ismail A, et al.
    Pharm Biol, 2021 Dec;59(1):964-973.
    PMID: 34347568 DOI: 10.1080/13880209.2021.1948065
    CONTEXT: Melicope latifolia (DC.) T. G. Hartley (Rutaceae) was reported to contain various phytochemicals including coumarins, flavonoids, and acetophenones.

    OBJECTIVE: This study investigates the antidiabetic and antioxidant effects of M. latifolia bark extracts, fractions, and isolated constituents.

    MATERIALS AND METHODS: Melicope latifolia extracts (hexane, chloroform, and methanol), fractions, and isolated constituents with varying concentrations (0.078-10 mg/mL) were subjected to in vitro α-amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory assay. Molecular docking was performed to study the binding mechanism of active compounds towards α-amylase and DPP-4 enzymes. The antioxidant activity of M. latifolia fractions and compounds were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and β-carotene bleaching assays.

    RESULTS: Melicope latifolia chloroform extract showed the highest antidiabetic activity (α-amylase IC50: 1464.32 μg/mL; DPP-4 IC50: 221.58 μg/mL). Fractionation of chloroform extract yielded four major fractions (CF1-CF4) whereby CF3 showed the highest antidiabetic activity (α-amylase IC50: 397.68 μg/mL; DPP-4 IC50: 37.16 μg/mL) and resulted in β-sitosterol (1), halfordin (2), methyl p-coumarate (3), and protocatechuic acid (4). Isolation of compounds 2-4 from the species and their DPP-4 inhibitory were reported for the first time. Compound 2 showed the highest α-amylase (IC50: 197.53 μM) and β-carotene (88.48%) inhibition, and formed the highest number of molecular interactions with critical amino acid residues of α-amylase. The highest DPP-4 inhibition was exhibited by compound 3 (IC50: 911.44 μM).

    DISCUSSION AND CONCLUSIONS: The in vitro and in silico analyses indicated the potential of M. latifolia as an alternative source of α-amylase and DPP-4 inhibitors. Further pharmacological studies on the compounds are recommended.

    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors/chemistry*
  16. Cao W, Chen X, Chin Y, Zheng J, Lim PE, Xue C, et al.
    J Food Biochem, 2021 Apr 04.
    PMID: 33817806 DOI: 10.1111/jfbc.13686
    Natural compounds have tremendous potential to regulate glucose metabolism, but conventional methods for studying their bioactivities are usually labor intensive. Here, hypoglycemic properties in 22 selected food-derived compounds were examined using molecular docking. The results indicated that curcumin is an inhibitor of both α-glucosidase and dipeptidyl-peptidase 4 (DPP-4), which are important for glycemic control. These effects of curcumin were also confirmed by enzymatic determination in vitro. Furthermore, curcumin significantly improved diet-induced hyperglycemia (e.g., fasting plasma glucose levels and glycogen storage in muscle or liver) in mice. This might be attributed to its inhibitory effects on the activities of α-glucosidase and DPP-4 in vivo. Curcumin also upregulated the expression of genes (e.g., glucagon-like peptide 1) related to DPP-4 activity in the small intestine. In conclusion, curcumin is a potential ingredient of functional foods used for diet-induced hyperglycemia management. PRACTICAL APPLICATIONS: Curcumin has been widely used as a colorant in the food industry. Moreover, a growing number of studies have described its diverse biological functions, such as anti-inflammatory, anti-oxidant, and anti-angiogenic activities. Thus, curcumin is regarded as a potential ingredient in functional foods. Our results highlighted the hyperglycemic effect of curcumin, suggesting that curcumin may be included in food products for hyperglycemic patients.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors
  17. Yap MKK, Misuan N
    PMID: 30417596 DOI: 10.1111/bcpt.13169
    Type II diabetes mellitus (T2DM) is a chronic non-communicable disease due to abnormal insulin actions causing uncontrolled hyperglycaemia. The treatment for T2DM, for instance, metformin and incretin mimetic, mainly focuses on the restoration of insulin sensitivity and secretion. Exendin-4 is a short incretin-mimetic peptide consisting of 39 amino acids. It is discovered in the venom of Heloderma suspectum as a full agonist for the glucagon-like peptide 1 (GLP-1) receptor and produces insulinotropic effects. It is more resistant to enzymatic degradation by dipeptidyl-peptidase-4 and has a longer half-life than the endogenous GLP-1; thus, it is further developed as an incretin hormone analogue used to treat T2DM. The helical region of the peptide first interacts with the extracellular N-terminal domain (NTD) of GLP-1 receptor while the C-terminal extension containing the tryptophan cage further enhances its binding affinity. After binding to the NTD of the receptor, it may cause the receptor to switch from its auto-inhibited state of the receptor to its auto-activated state. Exendin-4 enhances the physiological functions of β-cells and the up-regulation of GLP-1 receptors, thus reducing the plasma glucose levels. Moreover, exendin-4 has also been found to ameliorate neuropathy, nephropathy and ventricular remodelling. The therapeutic effects of exendin-4 have also been extrapolated into several clinical trials. Although exendin-4 has a reasonable subcutaneous bioavailability, its half-life is rather short. Therefore, several modifications have been undertaken to improve its pharmacokinetics and insulinotropic potency. This review focuses on the pharmacology of exendin-4 and the structure-function relationships of exendin-4 with GLP-1 receptor. The review also highlights some challenges and future directions in the improvement of exendin-4 as an anti-diabetic drug.
    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors
  18. Mak WY, Nagarajah JR, Abdul Halim H, Ramadas A, Mohd Pauzi Z, Pee LT, et al.
    PMID: 32566235 DOI: 10.1186/s40545-020-00238-y
    Background: In Malaysia, for more than a decade, dipeptidyl peptidase-4 inhibitors (DPP-4i) are among the oral antidiabetic medications used as monotherapy or in combination to manage type II diabetes mellitus (T2DM). These medications are known for the efficacy in glycated haemoglobin (HbA1c) reduction and weight neutral effect with minimal hypoglycaemia occurrence. This study aimed to identify the outcomes of DPP-4i use in one of the largest tertiary public hospital in Southeast Asia.

    Methods: This is a retrospective cross sectional study conducted in 2016, where stratified sampling method was used. Patients with T2DM treated with available DPP-4i; namely Linagliptin, Saxagliptin, Sitagliptin and Vildagliptin, for at least 3 months were identified from the pharmacy record. Medical records from Physician Clinic in Hospital Kuala Lumpur (HKL) were reviewed. Data on demographic, anthropometric, antidiabetic treatment modalities, laboratory and documented outcomes were collected. Outcomes endpoints which include changes in HbA1c, fasting blood glucose (FBG), and body weight were recorded and analysed. Adverse drug reactions (ADR) documented were also reported.

    Results and discussion: A total of one hundred and five patients were recruited. The patients were 49.5% men (n = 52), with a mean age of 57 years, mean HbA1c of 8.5% (69 mmol/mol) and mean BMI of 29.5 kg/m2. At least 50% of the patients had T2DM for more than 10 years and more than two third of these patients had both T2DM and hypertension. Thirty nine patients were on Vildagliptin, 32 on Sitagliptin, 26 on Saxagliptin and the remaining on Linagliptin. The most commonly prescribed DPP-4i were Vildagliptin and Sitagliptin. Majority of the patients (90.4%) were prescribed with Metformin, with 62.8% of patients on fixed-dose combination, and the remaining on add-on Metformin therapy. Use of DPP-4i as an adjunct was associated with a mean reduction of 0.9% (9 mmol/mol) in HbA1c (p 

    Matched MeSH terms: Dipeptidyl-Peptidase IV Inhibitors
  19. 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: Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
  20. 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: Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
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