Study of the Efficacy of Uptitrating Teneligliptin Dose from Standard Dose (20 mg) to High Dose (40 mg) in Patients with Type II Diabetes Mellitus

Purpose: To evaluate efficacy for an on-demand treatment of acute bleeding events, pharmacokinetics, safety, and tolerability of HemoRel-A® in severe hemophilia A. Methods: A total of 44 male subjects with severe hemophilia A with an annualized bleed rate of 12 while on-demand treatment with factor VIII (FVIII) were enrolled in the study and received HemoRel-A® for bleed treatment. The efficacy of HemoRel-A® was evaluated based on a four-point scale (excellent, good, moderate, or none). Six-point pharmacokinetic (PK) assessment was performed following a single dose of 50 IU/kg in 12 subjects after a 7-day wash-out period. Safety evaluations were performed at each visit and inhibitor testing was performed in all patients at screening and end of study. Results: Forty-four male subjects received at least a single dose of the study medication and were included in the intent-to-treat (ITT) analysis and safety outcome. In 23 (7.52%) out of the 306 bleeding events, HemoRel-A® efficacy was rated as excellent, in 272 (88.89 %) bleeds it was rated as good, and in 11 (3.68%) bleeding events it was rated as moderate. No failure of efficacy was noted in any of the bleeding events. Thus overall out of 306 bleeding events, 295 (96.41%) showed excellent or good efficacy. Pharmacokinetic assessment based on plasma FVIII activity measured by the chromogenic assay in 12 patients showed comparative results similar to FVIII preparations. A total of 12 adverse events (AEs) were reported in this study. There was no inhibitor development in this previously treated patients (PTP) cohort. Conclusion: HemoRel-A® was established to be efficacious and safe in the treatment of acute bleeding events in subjects with severe hemophilia A.

Prevalence of metabolic syndrome in an urban Indian diabetic population using the NCEP ATP III guidelines.

OBJECTIVE: To study the prevalence of metabolic syndrome (MetS) in an urban Indian diabetic population. RESEARCH DESIGN AND METHODS: A total of 5088 type 2 diabetes patients (2908 men and 2180 women) presenting to endocrinology clinics at four centers across Mumbai (a large metropolitan city in India) were selected for the study. Anthropometric (waist circumference), clinical (blood pressure) and biochemical (serum triglycerides, HDL, fasting and post-prandial blood glucose) data were recorded. Patients receiving treatment for hypertension or dyslipidemia were also included in the study and these were considered in the diagnosis of MetS even if the parameters were normal. The National Cholesterol Education Program Adult Treatment Panel III guidelines were used to diagnose MetS. The chi-square test was used to determine statistical significance, which was taken as a p value < 0.05. RESULTS: The prevalence of MetS among urban Indian diabetic patients was 77.2% and was significantly higher in women (87.71%) as compared to men (69.33%) (p < 0.0001). The most prevalent risk factors for MetS were hypertension, followed by hypertriglyceridemia, in men, and central obesity, followed by hypertension, min women. CONCLUSIONS: MetS is highly prevalent in the urban Indian diabetic population. It should be identified by regular screening in individuals from the general population to avert or delay the progression to type 2 diabetes in order to reduce diabetes-related morbidity and mortality.

Inter-generation comparison of type-2 diabetes in 73 Indian families.

AIMS AND OBJECTIVE: To study type 2 diabetics in 2 generations in the same family and to see if there are any significant differences in their presentations. The study also focused on the non-diabetic siblings to see if there were any differences between them. MATERIAL AND METHODS: Criteria for inclusion: 1. Proband case should have a parent who is a diabetic, 2. Proband case should have at least one sibling who is not diabetic. Entire families of such cases fulfilling the above criteria were included in the study. A detailed questionnaire was filled. This was followed by an examination of all anthropometric measurements like height, weight, waist circumference, hip circumference and blood pressure. Venous blood samples for glucose measurement (fasting and post prandial), HbA1c, renal profile, lipid profile and insulin levels were collected. Urine sample was collected in appropriate containers for microalbuminuria, albumin/creatinine ratio. RESULTS: The study included 73 families, with a total of 307 members (159 male and 148 female). 92 were from 1st generation and 215 from 2nd generation. Of these 182 were diabetics, 81 from 1st generation and 151 from 2nd generation (95 males and 87 females). 125 were non diabetics, 9 from 1st generation and 116 from the 2nd generation (64 males and 61 females). The mean age of onset of diabetes in 1st generation was 55.95 years (SD +/- 9.98) and in 2nd generation was 38.4 years (SD +/- 9.2) (p<0.0001). Body mass index (BMI), waist circumference, Wasist-hip ratio (W/H ratio) and triglycerides, HDL and blood pressure individually did not show any significant differences between the diabetics in both generations. The incidence of metabolic syndrome as per ATPIII criteria was 75.9 % among the 1st generation diabetics. There were only 9 non-diabetics in the first generation and this number was small to derive any statistical significance. Comparison between diabetics and non diabetics in the 2nd generation showed that the incidence of metabolic syndrome as per ATPIII criteria was significantly higher among the diabetics at 62.63% as against 28.45% in the non diabetics. BMI, W/H ratio and lipid profile individually did not show any significant differences between the diabetics and non diabetics. CONCLUSIONS: This study shows that the age of onset of diabetes is much earlier in the present generation being 38.4 years (SD +/- 9.2), as compared to 55.95 years (SD +/- 9.98) in the previous generation. There were no other significant differences between the two generations. In the present generation the incidence of metabolic syndrome as per ATPIII criteria was a significant risk factor for the development of diabetes. 62.63% of the diabetic siblings had metabolic syndrome as compared to 28.45% in the nondiabetic siblings. There were no other significant parameters for early detection of diabetes in this group.

Induction of long-term glycemic control in type 2 diabetic patients using pioglitazone and metformin combination.

AIMS AND OBJECTIVE: To study the effects of pioglitazone and metformin combination in type 2 diabetics in achieving long-term optimal glycemic control. METHODS AND MATERIALS: Patients whose duration of type 2 diabetes was less than 24 months were selected for the study. 373 such patients meeting the selection criteria were included in the study and were started on triple drug combination therapy. RESULTS: Three hundred seventy three (183 females and 190 males) patients were initiated on a triple drug combination of gliclazide 80 mg, tid, metformin 500 mg tid and pioglitazone 30 mg od. Once controlled, the doses of gliclazide were reduced if the blood glucose levels decreased. Those patients whose plasma glucose remained in the normal range for more than 6 months without the use of a sulphonylurea were considered to be in pharmacological remission. 48 patients were lost to follow up. At the beginning of the study the pre treatment biochemical parameters in these 325 diabetic patients at the time of enrolment were: average FBG of 209.44+/-73.82 mg/dl, PLBG 294.96+/-107.58 mg/dl, and HbA(1c) 11.21+/-3.85. The post treatment glycemic parameters were: FBG was 124.38+/-40.48 mg/dl (p < 0.0001), and PLBG 162.32+/-54.33 mg/dl (p < 0.001), average glycosylated hemoglobin was 6.45+/-2.17 (p < 0.001). After using the triple drug combination pharmacological remission was achieved in 36.3 percent i.e. 118 (60 males and 58 females) patients. The average time required for achieving remission was 4 (+/-3.3) months in males and 5 (+/-4.02) months in females. 118 patients were maintained remission after 2 years of follow up. The average duration of remission is 27 (+/-2.66) months. There was an average weight gain of 2.56 +/- 1.32 kg in both the groups of patients in remission and those who could not achieve remission. CONCLUSIONS: In this study we have found that we could achieve long term glycemic control 'pharmacological remission' in 118 of the 325 patients i.e.36% of type 2 diabetic patients. Insulin sensitizers like pioglitazone along with metformin may induce long-term glycemic control in type 2 diabetic patients.

Beneficial effects of triple drug combination of pioglitazone with glibenclamide and metformin in type 2 diabetes mellitus patients on insulin therapy.

BACKGROUND: The thiazolidinediones are a class of antidiabetes medication that enhance the actions of insulin in muscle, liver, and adipose tissue. Data have been lacking on their use in combination with both sulfonylurea and metformin among patients of type 2 diabetes who are on insulin therapy secondary to failure of routine oral hypoglycemic drugs in controlling their diabetes. OBJECTIVE: To determine the effects of pioglitazone in combination with sulphonylurea and metformin on diabetes control in patients being treated with insulin due to secondary failure of oral hypoglycemic agents. PATIENTS: One hundred and twenty-four consecutive type 2 diabetes patients (mean age, 57.13 years) attending four centres in Mumbai, who were being treated with insulin were selected. They were switched on to triple drug combination of glibenclamide 5 mg, metformin 500 mg and pioglitazone 15 mg along with insulin. Study participants were required to have type 2 diabetes mellitus for atleast 5 years. Patients were excluded if they had any of the following: serum creatinine concentration greater than 1.5 mg/dl, alanine aminotransferase (ALT) level more than two times the upper limit of normal, symptomatic angina, cardiac insufficiency or history of myocardial infarction. RESULTS: Pioglitazone 15 mg with glibenclamide 5 mg and metformin 500 mg, significantly decreased hemoglobin HbA1c level from 11.5% to 7.32% (P < 0.001), average fasting blood glucose from 194.8 mg/ dl to 124.06 mg/dl (p < 0.01), average post-prandial blood glucose from 256.24 to 162.32 mg/dl (p < 0.01). At 6 months, 43.35% of patients did not need to be continued on insulin. The total insulin requirement in 124 patients reduced by 71.81%. There were no significant side effects, liver enzymes were within acceptable levels, average weight gain was 2.23 kg, significant hypoglycemia was observed in 28 patients with two requiring hospitalisation, these patients were those who did not stick to follow-up schedules. CONCLUSIONS: With proper patient selection, pioglitazone with glibenclamide and metformin can be safely used in patients receiving insulin with good results.