PDB31 REIMBURSEMENT OF PHARMACEUTICALS AND BRANDGENERIC DRUG UTILIZATION: EVIDENCE FROM ORAL HYPOGLYCEMIC AGENTS FOR AMBULATORY CARE IN TAIWAN

Objective: The epidemic of T2DM is rising across the globe. Systemic inflammation plays a pivotal role in the pathogenesis and complications of T2DM. Combination of two or more oral hypoglycemic agents (OHA) is widely prescribed in patients with T2DM, however many patients have poor glycemic control despite receiving combination therapy. The new antidiabetic drugs are relatively costly or many patients have anxiety over the use of injectable insulin. The objective of this observational study was to investigate the effectiveness and tolerability of hydroxychloroquine (HCQ) in T2DM patients uncontrolled on multiple OHA and despite high sugar level not willing to initiate insulin therapy in a real-world clinical setting. Methods: A prospective, investigator-initiated, observational, single-centred study was conducted where 250 patients (18-65 years) with T2DM for more than 5 years, with uncontrolled glycemia despite on a combination of multiple OHA, HbA1c between ≥7% and <10.5%, FPG >130 mg/dL or PPG >180 mg/dL and BMI between >25 and <39 kg/m2, were prescribed hydroxychloroquine sulphate 400 mg once daily for 48 weeks. Percentage of drugs used at the baseline were as follows: metformin 2000 mg (100%), glimepiride 4 mg (100%), pioglitazone 30 mg (100%), sitagliptin 100 mg (100%), canagliflozin 300 mg (52.4%), empagliflozin 25 mg (22.8%), dapagliflozin 10 mg (17.6%) and voglibose 0.3 mg (62%). Mean change in HbA1c, blood glucose and hs-CRP at baseline, week 12, 24 and 48 were assessed using the paired t-test. Results: After 48 weeks of add-on treatment with HCQ, almost all SGLT-2 inhibitors were withdrawn; metformin dose was reduced to 1000 mg, glimepiride reduced to 1 mg and sitagliptin reduced to 50 mg OD. Patients continued to have good glycemic control. HbA1c was reduced from 8.83% to 6.44%. Reduction in FPG was 40.78% (baseline 177.30 mg/dL) and PPG was reduced by 58.95% (baseline 329.86 mg/dL). Change in mean body weight was -4.66 Kg. The reduction in glycemic parameters and mean body weight was significant (p < 0.0001). Hs-CRP was significantly reduced from 2.70±1.98 mg/L to 0.71±0.30 mg/L 9 (p < 0.0001). More reduction in glycemic parameters and body weight was observed among the patients with higher hs-CRP (> 3 mg/L) as compared to patients with baseline hs- CRP ≤ 3 mg/L. Most common adverse events reported with the drug therapy were GI irritation (3.6%) and hypoglycemia (2%). None of the patients required medical assistance for hypoglycemia. Conclusion: Add-on treatment of HCQ effectively improved glycemic control in T2DM patients uncontrolled on multiple antidiabetic drugs. By virtue of its antidiabetic and anti-inflammatory properties, it may emerge as a valuable therapeutic intervention for the patients with T2DM.

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Phenanthridine Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Design, Synthesis and Biological Evaluation

Current Computer - Aided Drug Design ◽

10.2174/1573409916666201007124122 ◽

2020 ◽

Vol 16 ◽

Author(s):

Reema Abu Khalaf ◽

Shorooq Alqazaqi ◽

Maram Aburezeq ◽

Dima Sabbah ◽

Ghadeer Albadawi ◽

...

Keyword(s):

Inhibitory Activity ◽

Biological Evaluation ◽

Ligand Docking ◽

Biological Assessment ◽

Hypoglycemic Agents ◽

Binding Affinities ◽

Oral Hypoglycemic Agents ◽

Design Synthesis ◽

Dpp Iv

Background: Diabetes mellitus is a chronic metabolic disorder, characterized by hyperglycemia over a prolonged period, disturbance of fat, protein and carbohydrate metabolism, resulting from defective insulin secretion, insulin action or both. Dipeptidyl peptidase-IV (DPP-IV) inhibitors are relatively a new class of oral hypoglycemic agents that reduces the deterioration of gut-derived endogenous incretin hormones that are secreted in response to food ingestion to stimulate the secretion of insulin from beta cells of pancreas. Objective: In this study, synthesis, characterization, and biological assessment of twelve novel phenanthridine sulfonamide derivatives 3a-3l as potential DPP-IV inhibitors was carried out. The target compounds were docked to study the molecular interactions and binding affinities against DPP-IV enzyme. Methods: The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR, and MS. Quantum-polarized ligand docking (QPLD) was also performed. Results: In vitro biological evaluation of compounds 3a-3l reveals comparable DPP-IV inhibitory activities ranging from 10%-46% at 100 µM concentration, where compound 3d harboring ortho-fluoro moiety exhibited the highest inhibitory activity. QPLD study shows that compounds 3a-3l accommodate DPP-IV binding site and form H-bonding with the R125, E205, E206, S209, F357, R358, K554, W629, S630, Y631, Y662, R669 and Y752 backbones. Conclusion: In conclusion, phenanthridine sulfonamides could serve as potential DPP-IV inhibitors that require further structural optimization in order to enhance their inhibitory activity.

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