300
`
`levels (from 54.7 ± 2.3 to 57.7 ± 2.7 mg/dl,
`serum HDL cholesterol
`P < 0.05)
`and serum adiponectin levels
`(from 8.27 ± 0.76 to
`9.13 ± 0.81 lg/ml, P < 0.05) increased significantly. Furthermore, plas-
`ma levels of interleukin-6 were significantly decreased (from 2.26 ± 0.27
`to 1.60 ± 0.14 pg/ml, P < 0.01) and levels of high sensitive C-reactive
`protein tended to decrease (from 0.088 ± 0.015 to 0.064 ± 0.010 mg/dl,
`P = 0.055). HOMA-IR also tended to decrease, but statistically not
`significant.
`Conclusions: These findings suggest that oral administration of telmi-
`sartan improve vascular
`inflammation and prevent atherosclerosis
`through the reduction in visceral fat accumulation and the increase in
`serum adiponectin concentrations.
`
`P819
`The efficacy and safety of pioglitazone plus a SU or
`metformin versus a fixed combination of metformin plus
`glibenclamide: results on lipid metabolism
`M Comaschi*, A Bellatreccia†, F Menozzi‡, C Barone‡ and S Mariz§
`*Public Health District, General Management, Genoa, Italy, †Takeda Italy,
`Clinical Researches, Rome, Italy, ‡La Colletta Hospital, Internal Medicine,
`Arenzano (Genoa), Italy, §Takeda Europe, Clinical Researches, London, UK
`
`Aims: Aim of this study was to compare the effectiveness on lipids of
`the co-administration of pioglitazone with either metformin or a
`sulphonylurea versus a fixed combination of metformin + sulphonylurea.
`Methods: This was a prospective, open, three-arm comparative, rand-
`omised study in patients with type 2 diabetes. After a 1-week run-in
`period, patients received either pioglitazone 15 mg once daily as add-on
`in patients receiving metformin or sulphonylurea or a fixed dose
`combination of metformin 400 mg and glibenclamide 2.5 mg twice a
`day. Pioglitazone could be increased to 30 mg/day and the fixed
`combination could be increased to three times a day at 15 days, 2 or
`4 months if the plasma glucose was >140 mg/dl or HbA1c was >7.5%.
`HDL-cholesterol, total cholesterol and triglycerides were measured at
`baseline and 6 months. 398 patients were screened and 250 were
`randomised into the trial. 103 patients were put ı`nto the pioglita-
`zone + metformin group, 77 into the pioglitazone + sulponylurea group
`and 80 into the fixed dose metformin + glibenclamide group.
`Results: HDL-cholesterol was significantly raised by 2.3 mg/dl from
`baseline in the pio + met group whereas there was a significant decrease
`of –3.3 mg/dl in the fixed dose combination group at 6 months. There
`was a significant difference in favour of both pio + met and pio + SU vs.
`fixed dose regarding HDL change. There were no differences between the
`groups for total cholesterol. A significant drop in triglycerides was only
`seen in the pio + SU group (28.3 mg/dl).
`Conclusions: This study showed that using pioglitazone in co-admin-
`istration with either metformin or sulphonylurea effectively improved
`diabetic dyslipidemia as compared with a worsening of HDL and no effect
`on other lipid parameters with the fixed dose combination. All three
`treatments were well tolerated with an increase in body weight seen in
`all three groups.
`
`P820
`Rosiglitazone in family practice, 6 years experience
`R Conway, D MacNair and B Patasi
`Canadian Centre for Research on Diabetes, Diabetes Clinic, Smiths Falls,
`Canada
`
`The first of a new class of oral hypoglycemic agents, rosiglitazone
`became available in Canada in Feb 2000. While there are published
`clinical trials, these have rigid inclusion and exclusion criteria. We set out
`to investigate how this new class of agent performed in a typical family
`practice which is where most type 2 diabetes is treated.
`Aims: To observe the performance and complications of rosiglitazone
`under typical family practice conditions without rigid inclusion or
`
`ª 2006 Diabetes UK, Diabetic Medicine, 23 (Suppl. 4), 200–410
`
`exclusion criteria. Since the UKPDS had shown an inevitable deterioration
`of beta cell function over time no matter what the treatment; of
`particular
`interest was whether
`treatment with this TZD led to
`preservation of beta cell function over a 5-year period.
`Methods: 500 type 2 diabetics who had failed to attain Canadian
`Diabetes Association targets for glycemic control on conventional agents
`and therefore had rosiglitazone added to their treatment regime are
`reported on in this unsupported observational study.
`Results: There was a progressive reduction in A1c. The initial 1.5%
`absolute A1c reduction seen by the sixth month of treatment has
`persisted for 5 years. There was no change in liver or kidney functions.
`Lipid parameters were stable. Drug discontinuation was similar to other
`reported studies at about 5%, the most common reason being fluid
`retention. Weight gain was minimal after all
`subjects
`received
`counseling on the potential
`for weight gain with the TZD drugs.
`Renal functions show a progressive decline in microalbuminuria, There
`is a small cohort of patients who have no glycemic response to
`Rosiglitazone, the reasons for this are not clear but need further
`investigation.
`Conclusions: Six years of experience has shown rosiglitazone to be a
`safe and effective drug for the treatment of type 2 diabetes, both in
`monotherapy and combination treatment. The persistence of
`the
`glycemic control
`improvement suggest that there may be beta cell
`preservation.
`Conclusions: Five years of experience has shown rosiglitazone to be a
`safe and effective drug for the treatment of type 2 diabetes, both in
`monotherapy and combination treatment. Persistence of glycemic
`improvement suggests beta cell preservation.
`
`P821
`Safety, tolerability, pharmacokinetics, and
`pharmacodynamics of BI 1356, a novel DPP-IV inhibitor
`with a wide therapeutic window
`K Dugi, S Huettner, U Graefe-Mody and A Ring
`Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany
`
`Background and Aims: Dipeptidyl peptidase IV (DPP-IV)
`inhibitors
`represent a new class of oral antidiabetic drugs. BI 1356 is a novel,
`orally available, selective, and potent inhibitor of DPP-IV in clinical
`development for the treatment of type 2 diabetes.
`Materials and Methods: The safety, tolerability, pharmacokinetics, and
`pharmacodynamics of BI 1356 were evaluated in a double-blind,
`randomised, placebo-controlled single-rising dose trial. Sixty-three
`healthy male volunteers between 21 and 65 years of age, received a
`single oral dose of 2.5–600 mg BI 1356 or placebo.
`Results: Treatment with BI 1356 was well tolerated. There were no
`serious adverse events, no episodes of hypoglycaemia, and no discon-
`tinuations due to adverse events. The most common adverse events
`reported in both, BI 1356 and placebo treated subjects, were headache
`and nausea. The overall incidence of adverse events was not different
`between BI 1356 and placebo. BI 1356 showed non-linear pharmaco-
`kinetics in the lower dose range with increasing clearance and volume of
`distribution, while dose-proportionality was observed over a dose range
`of 100–600 mg. Renal clearance represented a minor elimination
`pathway. A dose of 5 mg BI 1356 resulted in a mean inhibition of
`DPP-IV plasma activity of >80% of baseline 1.5 h after drug adminis-
`tration. BI 1356 plasma concentrations were directly correlated to
`plasma DPP-IV activity, resulting in a maximum inhibition ranging from
`73% to 97% for doses of 2.5–600 mg BI 1356, respectively, within 3 h
`after dosing.
`Conclusions: In summary, BI 1356 was well tolerated over the dose
`range 2.5–600 mg once daily in healthy male volunteers. BI 1356 has a
`wide therapeutic window of >100-fold based on a therapeutic dose of
`5 mg. The pharmacokinetic profile is consistent with a once daily dosing
`regimen.
`
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