Efficacy and Safety of HD-6277, a Novel G Protein-Coupled Receptor 40 Agonist, in Individuals with Type 2 Diabetes Mellitus: A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 2 Clinical Trial.

Aim: The main aim of the study is to compare the efficacy of add-on therapy of teneligliptin (20 once daily) versus pioglitazone (15 mg once daily) among type 2 diabetes mellitus (T2DM) patients inadequately controlled on dual therapy of metformin (MF) plus sulfonylurea (SU). Materials and Methods: It is a prospective, observational, comparative study conducted in patients from the outpatient department of Sri Bhadrakali Hospital located at Warangal, Telangana state, India. The efficacy of pioglitazone and teneligliptin was assessed by measuring the change in the glycated haemoglobin (HbA1c), Fasting Plasma Glucose (FPG), Post Prandial Blood Glucose (PPBH) levels after 12 weeks of treatment. FPG, PPBG and HbA1c levels at baseline and 12 weeks. The primary endpoint was changed in HbA1c levels at 12 weeks as compared to the baseline levels in both groups. The secondary endpoints were changes in FPG, PPBG levels at 12 weeks as compared to baseline levels. Along with, serum cholesterol, triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were measured both at baseline and after 12 weeks. Results: At study end, HbA1c levels were reduced from baseline by 0.7% (P = 0.0049) in the pioglitazone group and 1% (P = 0.0002) in the teneligliptin group. The mean changes in FPG levels from baseline to week 12 were −39.8 mg/dl (P ≤ 0.0001) in teneligliptin and −11.48 mg/dl (P = 0.00380) in pioglitazone group. The mean PPG levels from −47.8 mg/dl (P = 0.0003) in teneligliptin and −25.5 mg/dl (P = 0015) in pioglitazone group. After 12 weeks of study, the levels of TG, total cholesterol (TC), LDL −71.5 (P = 0.0973), −15 (P = 0.0501), 18.8 (P ≤ 0.0008) mg/dl and −31.38 (P ≤ 0.0001), −21 (P ≤ 0.0001), −11.68 (P = 0.0028) mg/dl in teneligliptin group and pioglitazone group, respectively. There was significant increase in HDL levels 5.3 (P ≤ 0.0001) mg/dl in teneligliptin group and 5.2 (P = 0.0001) mg/dl in pioglitazone group. Conclusion: Both teneligliptin 20 mg and Pioglitazone 15 mg provided additional HbA1c lowering to that achieved with MF and SU. Teneligliptin showed more effective reductions in HbA1c, FPG, PPBG, HDL and LDL levels. Pioglitazone showed significant changes in HbA1c, HDL, TC, triglyceride levels and significant changes in FPG, PPBG and LDL levels. Reduction in HbA1c and plasma lipids slows down the diabetes progression and decreases the risk of microvascular and macrovascular complications.

Objective: To assess the efficacy and safety of vildagliptin added to metformin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy.Methods: This was a 12-week prospective observational study where vildagliptin 50 mg twice daily was added to patients with T2DM inadequately controlled (glycosylated hemoglobin type A1c (Hba1c) 7–10%) by a daily dose of metformin ≥1700 mg between June 2012 and May 2013. Efficacy was assessed by change in Hba1c and fasting plasma glucose (FPG) levels, and safety was assessed by reported adverse events (AEs).Results: A total of 58 patients were enrolled in this study. Their age ranged between 39.0 and 71.0 years, with a mean of 52.6 years, and a standard deviation (SD) of 7.8. The average duration of diabetes mellitus (DM) was 4.0 years (SD 3.0) and half of the patients have had DM for more than three years. The mean baseline levels of Hba1c and FPG were 8% and 10.8 mmol/L, respectively. Patients treated with vildagliptin achieved clinically significant reductions in Hba1c of 1.1% (p value <.005) and reduction in FPG of 1.8 mmol/L (p value <.005) from baseline. Overall, 62.1% had achieved the target of Hba1c of <7% after vildagliptin use. Greater reductions in Hba1c were linked to higher baseline levels as well as to the daily frequency of metformin use. Mild AEs were reported by 16 patients. There was no incidence of hypoglycemia and there were no significant changes in body weight after treatment.Conclusions: Vildagliptin as add-on therapy to metformin improved glycemic control and was highly tolerable in T2DM patients who were inadequately controlled by metformin monotherapy.

Background and objectives: Type 2 diabetes mellitus (T2DM) is progressive multisystem disease requiring multiple antihyperglycaemic agents to attain or maintain glycaemic control. With the increase in incidence of T2DM and availability of a number of drugs as second line therapy there is considerable increase in the use of newer, more costly oral hypoglycaemic agents, which has resulted in substantial increase in associated costs to patients. The present study was aimed to evaluate the safety, efficacy and cost effectiveness of oral antidiabetic regimens. Methods: This study was an observational, prospective and longitudinal in nature carried out to study the safety, efficacy and cost effectiveness of three add on treatment regimens [i.e with sulfonylurea (group 1), glitazones (group 2) and dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) (group 3)] in patient with T2DM not controlled by metformin alone which included 150 subjects (approximately 50 patient in each group). The comparisons were conducted between these three groups for glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), post prandial glucose (PPG), costs and lipid profile. Results: At week 12, the significant reduction in HbA1c was found in group 1 (-1.19%) when compared to group 2 (-0.71%) and group 3 (-0.70%). Also significantly greater reductions were observed in group 1 in FPG level (-38.88%) when compared to group 3 and in PPG level (-54.08%) when compared to group 2 and group 3. Comparison of three groups showed significant increase in the cost in group 3 as compared to group 1 and group 2, with the highest cost effectiveness measured in group 1 (p<0.0001). Interpretation and conclusions: Group 1 resulted in significantly greater reductions in HbA1c, FPG and PPG levels and highest cost effectiveness when compared with group 2 and group 3 in patients with T2DM.

BackgroundReal-world studies on insulin degludec/aspart (IDegAsp) have been conducted in some Southeast Asian populations; however, data specific to Indonesia remain limited. The aim of this study was to evaluate the efficacy, safety profiles, and real-world clinical experience of IDegAsp after five years of implementation in diabetes care in Indonesia.MethodsThis five-year, single-center, open-label, prospective, non-interventional study included adults with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) who had been on IDegAsp treatment for at least 12 months. Glycemic and metabolic outcomes—glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial glucose (PPG), and body mass index (BMI)—were assessed at baseline, 3, 6, and 12 months. The safety was evaluated based on hypoglycemia incidence. Clinical rationale for IDegAsp initiation and regimen models were also documented.ResultsA total of 550 individuals (T1DM: 48; T2DM: 502) were included. At 12 months, both groups had significant reductions in HbA1c (T1DM: −3.60%, T2DM: −3.32%), FPG (T1DM: −119.39 mg/dL, T2DM: −105.60 mg/dL), and PPG (T1DM: −190.87 mg/dL, T2DM: −180.10 mg/dL) (all p < 0.001 compared to baseline). Slight but statistically significant increases in BMI were observed in both groups (both p < 0.001). No episodes of hypoglycemia were reported among T1DM patients, whereas in the T2DM cohort, it occurred in 3.0% of cases comprising 1.4% with a single episode and 1.6% with two episodes with no severe hypoglycemia reported. The most frequent reasons for initiating IDegAsp included suboptimal HbA1c and PPG levels, with T2DM patients more often citing the need for flexible injection time or schedule.ConclusionIDegAsp demonstrated sustained glycemic improvement at 3-, 6-, and 12-months follow-ups with a favorable safety profile over one year, in both T1DM and T2DM populations in Indonesia. These findings support its utility in routine clinical practice, particularly among patients with unmet glycemic targets or complex treatment needs.

2359-PUB: Clinical Effectiveness of Canagliflozin 100mg in T2DM Patients—A Real-World Study

107-LB: Relative Contribution of Fasting Plasma and Postprandial Glucose to HbA1c and TIR in People with T1D on Basal-Bolus Insulin Therapy

ADVERTISEMENT RETURN TO ISSUEPREVPatent HighlightNEXTGPR40 Receptor Agonists for the Treatment of Type 2 Diabetes and Related DiseasesAhmed F. Abdel-Magid*Ahmed F. Abdel-MagidTherachem Research Medilab, LLC., 100 Jade Park, Chelsea, Alabama 35043, United States*E-mail: [email protected]More by Ahmed F. Abdel-MagidCite this: ACS Med. Chem. Lett. 2018, 9, 9, 870–871Publication Date (Web):August 13, 2018Publication History Received27 July 2018Published online13 August 2018Published inissue 13 September 2018https://pubs.acs.org/doi/10.1021/acsmedchemlett.8b00343https://doi.org/10.1021/acsmedchemlett.8b00343editorialACS PublicationsCopyright © 2018 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views1638Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (441 KB) Get e-AlertscloseSUBJECTS:Anatomy,Carbohydrates,Diabetes,Peptides and proteins,Receptors Get e-Alerts

IDF21-0679 INTENSIFY: effectiveness of insulin degludec/liraglutide (IDegLira) in a real-world T2DM population in the UAE

The purpose of this study was to clarify the predictive clinical characteristics of therapy switching from sitagliptin to dulaglutide in patients with type 2 diabetes mellitus. This single-center, open-label, investigator-initiated pilot study was conducted in 40 patients with type 2 diabetes mellitus. The patients, who had been treated with 50mg sitagliptin daily for at least 6months were switched to 0.75mg dulaglutide weekly. A total of 36 patients could be followed for 24weeks of treatment with dulaglutide. They were assessed for several clinical parameters before the start of and 24weeks after the study. Multiple linear regression analysis was used to search for independent predictors of reduction of hemoglobin A1c (HbA1c) levels after 24weeks of treatment switching from sitagliptin to dulaglutide. Dulaglutide administration for 24weeks resulted in significant reductions in fasting plasma glucose (FPG), HbA1c, and low-density lipoprotein cholesterol (LDL-C) levels. In addition, baseline HbA1c, FPG, body mass index (BMI), and age were significantly correlated with the change in HbA1c levels (ΔHbA1c). Furthermore, multiple linear regression analysis revealed that BMI and age significantly correlated with ΔHbA1c. In summary, our prospective 24-week study showed that baseline low BMI and old age are significantly useful in predicting the HbA1c-lowering effect of switching from sitagliptin to dulaglutide. UMIN Clinical Trials Registry (UMIN000023245).

IntroductionPatients with type 2 diabetes mellitus (T2DM) who cannot achieve normal glycosylated hemoglobin (HbA1c) levels are sometimes given the combined therapeutic regimen of polyethylene glycol loxenatide (PEG-Loxe) + basal insulin. The aim of this study was to investigate the efficacy and safety of PEG-Loxe combined with basal insulin in patients with T2DM.MethodsThis retrospective, real-world study included patients with T2DM aged ≥ 18 years for whom basal insulin therapy was ineffective, whose HbA1c levels were between 7.0% and 11.0%, and who were on either continued basal insulin dose adjustment or who had received PEG-Loxe + basal insulin combined therapy for at least 24 weeks. The primary endpoint was change in HbA1c level after 24 weeks treatment. Secondary endpoints included HbA1c achievement target rate, change in fasting plasma glucose and body weight, respectively, and change in HbA1c stratified by sex, age, disease duration, and baseline HbA1c level.ResultsOverall, 307 patients were identified. After propensity score matching, 44 patients each were included in the basal insulin and PEG-Loxe + basal insulin group. After 24 weeks, a significant difference in Hb1Ac reduction between the groups (P = 0.003) was observed. Also, patients treated with PEG-Loxe + basal insulin combined therapy experienced greater body weight reduction compared those treated with basal insulin only (intergroup difference: − 3.2 kg; 95% confidence interval [95% CI] − 5.4, − 1.0]; P = 0.005). There was a significant intergroup difference in weight reduction in patients with body mass index ≥ 28 kg/m2 (− 8.4 kg; 95% CI − 13.9, − 3.0; P = 0.004). HbA1c levels in female patients aged < 65 years with HbA1c ≥ 8.5% and with a disease duration ≥ 10 years were significantly different between the two treatment groups (P < 0.005). Hypoglycemic events occurred in 10.4% of patients treated with PEG-Loxe + basal insulin with no cases of level 3 hypoglycemia.ConclusionPEG-Loxe + basal insulin combined therapy was safe and effective in patients with T2DM who did not achieve optimal glycemic control with insulin therapy alone.Trial RegistrationClinicalTrials.gov identifier: ChiCTR2400086699.

IntroductionThe efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations; however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa.MethodsThe ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5–10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed.ResultsA total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (− 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event.ConclusionIn people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions.ClinicalTrials.gov identifierNCT03760991.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01271-7.

The aim of the present 24-week multicentre randomized non-inferiority trial was to compare the efficacy and safety of two insulin intensification strategies in uncontrolled type 2 diabetes despite optimized basal insulin therapy. Patients with fasting plasma glucose (FPG) <130 mg/dL and HbA1c 7.0%-10.0% while on insulin glargine were randomized to a basal-prandial group (stepwise addition of insulin glulisine) or a premixed insulin group (insulin aspart/insulin aspart protamine 30/70 starting with 6 IU twice daily). The primary endpoint was the change in HbA1c after 24 weeks (non-inferiority margin 0.4%). At Week 24, the adjusted mean change from baseline HbA1c was -0.94 ± 0.09% and -1.04 ± 0.09% in basal-prandial and premixed insulin groups, respectively, with a mean difference of -0.09% (95% confidence interval [CI] -0.35, 0.16). A lower rate of hypoglycemia with a similar reduction in HbA1c was observed during stabilization of the total daily insulin dose in the premixed insulin group (Weeks 0-12). After stabilization of the total daily insulin dose, the rate of hypoglycemia and the total daily insulin dose were similar in the two groups. The efficacy and safety of the two intensifying regimens were similar after stabilization of the total daily insulin dose when oral agents were maintained. Starting with a lower total daily insulin dose with a gradual change in the treatment regimen was helpful in reducing the rate of hypoglycemia during initial stabilization of the total daily insulin dose.

Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose

Teneligliptin is a recently developed Dipeptidyl Peptidase 4 (DPP4) inhibitor. Teneligliptin is suitable for glycaemic control with renal impairment including end stage renal disease. To assess the efficacy and safety of teneligliptin in Asian Indian patients of Type 2 Diabetes Mellitus (T2DM) with early Diabetic Kidney Disease (DKD). This was a single centre, retrospective analysis of patients with early DKD, who received teneligliptin 20 mg once daily for 24 weeks. Data related to glycaemic parameters, kidney function, lipid levels, retinopathy, neuropathy and safety variables available at 12 and 24 weeks were analysed. Descriptive statistical analysis was carried out. Statistical significance was assessed at a 5% level. Total 37 patients (21 males; 16 females) were analysed. Compared to baseline, significant reduction in Fasting Plasma Glucose (FPG) (mg/dl) (143.89±28.26 vs. 125.78±20.52, p=0.001); Postprandial Glucose (PPG) (mg/dl) (200.62±41.88 vs. 165.76±26.02, p=0.001); Glycated Haemoglobin (HbA1c) (%)(8.65±0.58 vs. 8.17±0.54, p=0.001) was noted at 12 weeks. This trend was further continued for 24 weeks with significant reduction in mean FPG, PPG and HbA1c to 113.73±16.82 mg/ dl (p=0.008); 142.95±20.76 mg/dl (p=0.001); and 7.65±0.45% (p=0.001) respectively. Significant improvement in serum creatinine (mg/dl) (2.45±0.27 vs. 2.26±0.23, p=0.001) and eGFR (CKD-EPI), (ml/min/1.73 m2) (53.35±4.24 vs. 55.08±4.19, p=0.001) was noted at 12 weeks and continued for 24 weeks with reduction in serum creatinine of 0.37±0.18 mg/ dl (p=0.001) and increase of eGFR of 4.60±1.59 ml/min/1.73 m2 (p=0.001). At baseline, proteinuria was noted in all patients while at 24 weeks, 40.5% (p=0.001) patients did not report proteinuria. Significant improvements in lipid parameters with no deterioration in retinopathy and subjective improvement in peripheral neuropathy was also noted. No adverse events were noted. Teneligliptin reported significant and sustained improvement in glycaemic control in Asian Indian Patients of T2DM with early DKD and was well tolerated. Additionally, Teneligliptin reported significant improvement in renal function.

A randomized clinical trial comparing basal insulin peglispro and insulin glargine, in combination with