Analysis of the 5-HT2 Receptor Ligands Dimethoxy-4-indophenyl-2-aminopropane and Ketanserin in Ethanol Discriminations

Previous studies have suggested a modulatory role of the 5-HT₂ receptor system in the behavioral effects of ethanol. The present study examined the discriminative stimulus effects of the 5-HT_2A/2C agonist (–)-dimethoxy-4-indophenly-2-aminopropane (DOI) and the 5-HT_2A antagonist ketanserin in rats trained to discriminate either 1.5 g/kg of ethanol from water (intragastrically, n = 7) or 2.0 g/kg of ethanol from water (intragastrically, n = 8). In substitution tests, neither DOI (0.3 to 1.0 mg/kg, ip) nor ketanserin (3.0 to 17.0 mg/kg, ip) produced discriminative stimulus effects similar to either training dose of ethanol, although decreases in rates of responding were significant at the highest doses tested. Likewise, when given in combination with ethanol, neither 5-HT₂ ligand shifted the ethanol-dose response determination in either the 1.5 or 2.0 g/kg ethanol training groups. DOI in combination with ethanol did not alter rates of responding, whereas ketanserin in combination with ethanol significantly decreased response rates. Thus, the 5-HT_2A receptor ligands do not appreciably affect the discriminative stimulus effects of ethanol, in contrast to previous results with 5-HT_1B ligands.     

Use of the TWEAK Test in Screening for Alcoholism/ Heavy Drinking in Three Populations

TWEAK is an acronym for Tolerance (T ₁ number of drinks to feel high; T₂, number of drinks one can hold), Worry about drinking, Eye-opener (morning drinking), Amnesia (blackouts), and Cut down on drinking (K/C). In this study, two versions ( T ₁ and T ₂) of the TWEAK were part of a questionnaire used to detect alcoholism or heavy alcohol intake in three populations, namely, alcoholics in treatment, patients in two outpatient clinics, and the general population. Similar to the CAGE and the 10-item brief MAST, the TWEAK identified most known alcoholics, but the TWEAK had a higher sensitivity and specificity than the CAGE and B-MAST in detecting alcoholism/heavy drinking in the clinical and general populations. Different cut-off values for tolerance ( T ₁ and T ₂) are recommended for screening different populations.     

Possibility of 5-HT3 Receptor Involvement in Alcohol Dependence: A Microdialysis Study of Nucleus Accumbens Dopamine and Serotonin Release in Rats with Chronic Alcohol Consumption

The present study was performed to examine the involvement of serotonin-3 (5-HT3) receptors in the rat nucleus accumbens (ACC) in alcohol dependence. In alcohol-treated rats, perfusion of 40 mM K⁺ and 100 mM ethanol (EtOH) through the microdialysis probe increased the extracellular levels of ACC dopamine (DA), compared with controls. Perfusion of the serotonin (5-HT) uptake inhibitor sertlarine enhanced the extracellular levels of ACC 5-HT in both groups. Increased 5-HT availability in the synaptic clefts on the ACC further activated ACC DA release in the alcohol-treated rats, in comparison with controls. In the final experiments, perfusion of the 5.0 μ M 5-HT₃ receptor agonist 2-methyl-5-HT (2-Me-5-HT) through the microdialysis probe enhanced the extracellular levels of ACC DA. Magnitude of 2-Me-5-HT-induced DA release was significantly higher in alcohol-treated rats than in controls. On the other hand, 40 mM K⁺- and 100 mM EtOH-induced extracellular 5-HT release in alcohol-treated rats were markedly inhibited. These results show that (1) chronic alcohol intake increases the sensitivity of 5-HT₃ receptors, (2) 5-HT₃ receptors regulate DA release in the ACC, (3) the dopaminergic neuronal systems associated with 5-HT₃ ionophore in the ACC were upregulated after chronic alcohol exposure, and (4) chronic alcohol intake desensitizes the serotonergic neuronal systems in rat ACC. These findings suggest that neurochemical functions of 5-HT₃ receptors in regulating DA release in the ACC after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original properties in processing alcohol tolerance and that the development of alcohol dependence may be mediated by ACC 5-HT₃ receptors.     

The 5-HT3 Antagonist MDL-72222 Exacerbates Ethanol Withdrawal Seizures in Mice

Ethanol-dependent mice were treated with the 5-HT₃ antagonist MDL 72222 after withdrawal from ethanol. Treatment with unit doses (0, 5.6, 10, and 17.0 mg/kg) of MDL 72222 at 0, 4, and 7 hr after withdrawal dose-dependently exacerbated the severity of ethanol withdrawal seizures. Treatment with a single dose (17 mg/kg) of MDL 72222 at 5 hr after withdrawal also exacerbated the severity of ethanol withdrawal seizures. Ethanol naive mice treated with MDL 72222 (56 mg/kg) did not display any seizures. Treatment with another 5-HT₃ antagonist, ICS 205-930 (23 and 46 mg/kg), or the 5- HT₂ receptor antagonist ketanserin, did not affect ethanol withdrawal seizures. The findings suggest MDL 72222 selectively enhances sensitivity to withdrawal seizures following chronic ethanol exposure.     

Treatment of Reflux Esophagitis Resistant to H2-Receptor Antagonists with Lansoprazole, a New H+/K+-ATPase Inhibitor: A Controlled, Double-Blind Study

This multicenter, randomized, double-blind, 8-wk study compared the new H⁺/K⁺-ATPase inhibitor, lansoprazole, 30 mg daily, to ranitidine 150 mg bid for treatment of erosive reflux esophagitis resistant to his-tamine-2 receptor antagonists (H2RA). Patients were evaluated after 2, 4, 6, and 8 wk of treatment by symptom assessment and endoscopy. Healing rates for lansoprazole were 71%, 80%, 88%, and 89% at 2, 4, 6, and 8 wk, respectively, compared to 21%, 33%, 45%, and 38% for ranitidine ( p < 0.001 at all points). Lansoprazole was significantly more effective than ranitidine for relief of heartburn and reduction of antacid tablet use. Increases in serum gastrin concentrations between the baseline and the 8-wk visit were greater in lansoprazole-treated than in ranitidine treated patients. Lansoprazole was safe and well tolerated. In patients with erosive reflux esophagitis resistant to standard doses of H2RA, lansoprazole 30 mg/day is more effective than continuation of an H2RA (ranitidine 150 mg bid) for healing of esophagitis and improvement of symptoms.     

Effect of Warfarin Anticoagulation on Vitamin-K1 Metabolism in Man

S ummary . Three normal men were injected intravenously with 1 mg [1',2'-³H₂]-vitamin K₁ before and after treatment with therapeutic doses of warfarin for 8–10 days. Warfarin treatment caused a delayed clearance of lipid-soluble radioactivity from the plasma. This was found to be due to the accumulation in the plasma of a metabolite with the properties of vitamin K₁ oxide as shown by thin-layer chromatography: the rate of clearance of vitamin K₁ from the plasma was not affected. Under warfarin treatment there was about a two-fold increase in the urinary excretion of radioactivity.     

A pilot double-blind treatment trial of memantine for alcohol dependence

BACKGROUND: There is growing evidence that N-methyl-d-aspartate (NMDA) receptor antagonists may have potential for the treatment of alcohol disorders. Memantine is a selective noncompetitive NMDA receptor antagonist that has been shown to decrease alcohol craving in moderate drinkers. This 16-week double-blind outpatient pilot clinical trial determined if memantine was more effective than placebo at reducing alcohol use in actively drinking alcohol-dependent patients. METHODS: Forty-four treatment-seeking alcohol-dependent individuals were enrolled, with 34 patients stratified to either the memantine group (n=19; maximum dose of 40 mg/d) or the placebo (PBO; n=15) group. The primary outcome measures were related to alcohol use (average drinks per day, average drinks per drinking day, percentage of heavy drinking days, and percentage of days abstinent) based on the timeline follow-back (TLFB). Secondary outcome measures included the Obsessive Compulsive Drinking Scale, Clinical Global Impression ratings, and gamma-glutamyltransferase (GGT), a biomarker of recent alcohol use. To enhance retention, patients received voucher incentives for clinic attendance. RESULTS: Of those randomized, approximately 80% (27) completed the entire 16-week trial. Longitudinal analysis of drinks per day and drinks per drinking day showed a significant reduction in alcohol use, but no difference between the 2 groups. Further, the percentage of heavy drinking days indicated that both groups showed a significant decrease in drinking behavior, but there was significant treatment effect in favor of the PBO group. Similarly, for the percentage of days abstinent, the PBO group achieved a significantly greater percentage of days abstinent at a faster rate than the memantine group. Lastly, the memantine group reported a greater number of side effects compared with the PBO group, such that 26% of patients had their drug dose decreased or discontinued due to memantine-related side effects. CONCLUSIONS: The results of this double-blind placebo-controlled pilot trial do not support the use of memantine for the treatment of actively drinking alcohol-dependent patients. However, voucher incentives did facilitate retention.     

Co-administration of SR141716 with peptide YY3-36 or oxyntomodulin has additive effects on food intake in mice

Background:  SR141716 has been shown to significantly inhibit food intake and reduce body weight by antagonizing CB₁ receptors. The gut hormones peptide YY_3–36 (PYY_3–36) and oxyntomodulin (OXM) inhibit food intake through Y₂ and Glucagon-Like-Peptide (GLP)-1 receptors respectively.
Objective:  To determine the effects of co-administration of SR141716 with either PYY_3–36 or OXM in mice on food intake.
Methods:  Mice (n = 14 per group) were fasted for 16 h prior to study days and given two intraperitoneal injections: study 1, vehicle–saline, SR141716–saline, vehicle–PYY3–36 or SR141716–PYY3–36; study 2: vehicle–saline, SR141716–saline, vehicle–OXM or SR141716–OXM.
Food was returned and measured following injections.
Results:  Co-administration of SR141716–PYY_3–36 or SR141716–OXM showed greater inhibition in food intake when compared with administration of SR141716, PYY_3–36 or OXM alone.
Conclusion:  Our data show that SR141716 in combination with PYY_3–36 or OXM reduces food intake additively in mice.     

Decreasing levels of tumour necrosis factor alpha and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors

Aim:   Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F_2α during BMI lowering with orlistat (Xenical^®, Roche) or placebo.
Methods:   TNF-α, IL-6, and 8-epi PGF_2α evaluated in 376 subjects aged 18–75 years with BMI 28–38 kg/m² before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily.
Results:   Weight reduction was associated with decreasing (p < 0.001) levels of TNF-α and IL-6 in both orlistat and placebo groups. After 12 months, TNF-α was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-α correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF_2α correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001).
Conclusion:   Weight reduction was associated with decreasing levels of both TNF-α and IL-6. After 12 months of treatment, TNF-α levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.     

Dopamine D2 Receptor Gene Expression in Rat Lines Selected for Differences in Voluntary Alcohol Consumption

A selective breeding program has led to the establishment of the alcohol-preferring AA (Alko, Alcohol) and alcohol-avoiding ANA (Alko, Nonalcohol) rat lines. To reveal putative baseline differences in dopamine receptor gene expression and dopamine receptor binding profile in the AA and ANA rat lines, we assessed striatal D₂ mRNA levels in these two rat lines. Autoradiographical studies on dopamine D₁ and D₂ receptors in the striatum and nucleus accumbens were also performed with [³H]SCH 23390 and [¹²⁵I]iodosulpiride/[³H]spiperone, respectively. The baseline differences in D₁ or D₂ receptor binding and D₂ receptor gene expression between AA and ANA rat lines are marginal, and are not likely to play a role in the genetic background of the differential alcohol drinking behavior of these rat lines.     

Pulmonary gas exchange in the morbidly obese

The literature on pulmonary gas exchange at rest, during exercise, and with weight loss in the morbidly obese (body mass index or BMI ≥ 40 kg m⁻²) is reviewed. Forty-one studies were found (768 subjects weighted mean = 40 years old, BMI = 48 kg m⁻²). The alveolar-to-arterial oxygen partial pressure difference (AaDO₂) was large at rest in upright subjects at sea level (23, range 5–38 mmHg) while the arterial pressure of oxygen (PaO₂) was low (81, range 50–95 mmHg). Arterial pressure of carbon dioxide (PaCO₂) was normal. At peak exercise (162 W), gas exchange improves. Weight loss of 45 kg (BMI = −13 kg m⁻²) over 18 months is associated with an improvement in PaO₂ (by 10 mmHg, range 1–23 mmHg), a reduction in AaDO₂ (by 8 mmHg, range −3 to −16 mmHg), and PaCO₂ (by −3 mmHg, range 3 to −14 mmHg) at rest. Every 5–6 kg reduction in weight increases PaO₂ by 1 and reduces AaDO₂ by 1 mmHg, respectively. Morbidly obese women have better gas exchange at rest compared with morbidly obese men which is likely due to lower waist-to-hip ratios in women than from differences in weight or BMI.     

Comparative Automated Assay of Anti-P1 Antibodies in Acute Hepatic Distomiasis (Fascioliasis) and in Hydatidosis

Abstract. An automated assay of anti-P₁ allohemagglutinins has been carried out on 133 P₂ subjects: 13 with acute hepatic distomiasis (Fascioliasis), 20 with hydatidosis and 100 healthy blood donors. Anti-P₁ were detected in 100% of the distomatid sera, in 50% of the hydatid and in 29% of the healthy individuals. When compared to a reference serum test (anti-P₁ standard), their concentration was found to be weak in healthy subjects, moderate in hydatidosis and exceptionally increased in acute distomiasis (up to 5–6 times the standard anti-P₁ level). The 2-mercaptoethanol treatment showed that even the increased distomatid anti-P₁ sera were of an IgM nature. The respective origin, synthesis and strength of these allohemagglutinins are discussed and the advantages of using distomatid IgM anti-P₁ as human sera test are emphasized.     

Blood group A1 and A2 revisited: an immunochemical analysis

Background and Objective  The basis of blood group A₁ and A₂ phenotypes has been debated for many decades, and still the chemical basis is unresolved. The literature generally identifies the glycolipid chemical differences between blood group A₁ and A₂ phenotypes as being poor or no expression of A type 3 and A type 4 structures on A₂ red cells, although this assertion is not unanimous.
Materials and Methods  Using purified glycolipids and specific monoclonal antibodies, we revisited the glycolipid basis of the A₁ and A₂ phenotypes. Purified glycolipids were extracted from four individual A₁ and four individual A₂ blood units. One blood unit from an A weak subgroup was also included. Monoclonal anti-A reagents including those originally used to define the basis of A₁ and A₂ phenotypes were used in a thin layer chromatography – enzyme immunoassay to identify the presence of specific glycolipids.
Results  A type 3 glycolipid structures were found to be present in large amounts in all phenotypes. In contrast, the A type 4 glycolipid structure was virtually undetectable in the A₂ phenotype, but was present in the A₁ and A subgroup samples.
Conclusion  The major glycolipid difference between the A₁ and A₂ phenotypes is the dominance of A type 4 glycolipids in the A₁ phenotype.     

Sertraline in the treatment of co-occurring alcohol dependence and posttraumatic stress disorder

BACKGROUND: Posttraumatic stress disorder (PTSD) frequently co-occurs with alcohol use disorders. This study investigated the use of sertraline, a serotonin reuptake inhibitor, in treating co-occurring symptoms of alcohol dependence and PTSD. METHODS: A total of 94 individuals with current alcohol dependence and PTSD were randomly assigned to receive sertraline (150 mg/day) or placebo for 12 weeks. Post hoc cluster analysis of baseline characteristics was used to define subgroups of participants. RESULTS: There was a significant decrease in alcohol use during the trial in both the sertraline and the placebo groups. Cluster analysis revealed significant medication group by cluster interactions for alcohol-related outcomes. Sertraline-treated participants with less severe alcohol dependence and early-onset PTSD had significantly fewer drinks per drinking day (p < 0.001). For participants with more severe alcohol dependence and later onset PTSD, the placebo group had significantly greater decreases in drinks per drinking day (p < 0.01) and average number of drinks consumed per day (p < 0.05). CONCLUSIONS: There may be subtypes of alcohol-dependent individuals who respond differently to serotonin reuptake inhibitor treatment. Further investigation of differential responders may lead to improvements in the pharmacological treatment of co-occurring alcohol dependence and PTSD.     

Haemoglobin A1 in Diabetes Mellitus

Summary: Haemoglobin A₁ in diabetes mellitus. P. C. Bartley and T. E. Hambling
HbA₁ was measured by a rapid method in a routine hospital laboratory. The normal range of 5·0–8·5% compares favourably with other studies. Patients with uncontrolled diabetes had levels of HbA₁ of up to 20·5% while well controlled patients had levels of HbA₁ in the normal range. The level of HbA₁ is relatively stable in normal subjects and does not correlate with age, sex or weight. There was a correlation (p < 0·001) with a 1–2 hour postprandial, post-insulin blood sugar in insulin dependent diabetics. There was a relationship between type of therapy and HbA₁ level at presentation. From the study of two ketoacidotic patients, it is apparent that the level of HbA₁ decreases about six weeks after the decrease in blood sugar. It is concluded that the measurement of HbA₁ is a useful adjunct in the assessment of diabetic control.     

Selective Inhibition of Alcohol Intake in Diverse Alcohol-Preferring Rat Strains by the 5-HT2A Antagonists Amperozide and FG 5974

The present studies sought to elucidate the role of 5-HT_2A receptor antagonists in suppressing alcohol intake by comparing the effects of amperozide and FG 5974 on alcohol, food, and water intake in strains of alcohol-preferring rats: P, Alko Alcohol (AA), and Fawn-Hooded (FH). Both amperozide and FG 5974 have 5-HT_2A receptor antagonist properties, but FG 5974 also shows presynaptic 5-HT_1A receptor agonist activity. After establishment of stable baselines for intake measures in a two-bottle continuous access paradigm, rats ( n = 10) were injected with 1 of 5 doses (0, 1.0, 2.5, 5.0, and 10.0 mg/kg, sc) of amperozide or FG 5974 at weekly intervals. Amperozide dose-dependently reduced alcohol intake, total fluid intake, and alcohol preference in all three strains under continuous access conditions, whereas FG 5974 was less effective. Food intake was also suppressed by amperozide at higher doses, whereas it was increased by FG 5974. Amperozide also dose-dependently reduced alcohol intake when it was available for only 1 hr/day, but FG 5974 tended to increase it. After oral administration, amperozide was also more effective than FG 5974 in reducing alcohol intake. Despite these differences in efficacy in suppressing alcohol intake, both compounds produced taste aversion to a novel saccharin solution. These complex findings suggest that biochemical properties other than 5-HT_2A receptor antagonism (e.g., 5-HT_1A receptor agonism) may be involved in the effects of amperozide and FG 5974 on alcohol intake and other consummatory behaviors.     

Serum 'Uracil+Uridine'Levels Before and After Vitamin B12 Therapy in Pernicious Anaemia

S ummary . The serum 'uracil+uridine'levels, expressed as uracil, have been measured in 10 cases of pernicious anaemia both before and after treatment, and compared with the levels in 97 normal subjects. The mean pre-treatment value (8.82 μmol/l., range 6.0–12.0 μmol/l.) differed significantly from that of the normal controls (15.7 μmol/l., range 5.7–40.5 μmol/1., t = 8.8, P <0.001). This confirms the low serum uracil level previously reported in pernicious anaemia in relapse. The level rose progressively after treatment, reaching a maximum on the fourth day (mean 17.85 μmol/1., range 9.3–23.4 μmol/l.). This was not significantly different from the mean of the normal control group. The difference between the pre- and post-treatment levels was significant on days 3, 4 and 5 ( P <0.005, P <0.001 and P <0.005 respectively) and the rise preceded the reticulocyte response by 24 h. A further case was treated with physiological doses of vitamin B₁₂ (2 μg daily for 6 d) and a similar rise in the serum uracil level noted.
These results are not explained by any of the known functions of vitamin B₁₂. They are, however, similar to the changes in the serum methionine levels previously reported in pernicious anaemia. The latter were readily explained by the known action of vitamin B₁₂ on ' de novo 'methionine synthesis and it is suggested that the synthesis of uracil, like that of methionine, might be influenced by vitamin B₁₂ in man.     

Ethanol Has Direct Inhibitory Effects on Steroidogenesis in Human Granulosa Cells: Specific Inhibition of LH Action

We have evaluated the direct effects of ethanol (EtOH) on the production of progesterone (P) and estradiol-17β (E₂) by cultured human granulosa cells obtained during in vitro fertilization procedures. On day 3 of culture, cells were divided into control and ethanol (20 m m ) groups and stimulated by hFSH (50 ng/ml), h lh (0–50 ng/ml), FSH+LH, 8 Br-cAMP (0.25 m m ) and androstenedione (10⁻⁷ M). Experiments were terminated on days 7 and 9 and DNA, P, and E₂ were measured. Ethanol inhibited P and E₂ secretion stimulated by LH; however, there was no significant effect of ethanol on P and E₂ production in the control group or when the cells were stimulated by FSH or cAMP. EtOH also had no effect on androstenedione stimulated E₂ production. There was no significant difference in the DNA contents of the human granulosa cells in the ethanol group as compared with the control group. These results are the first demonstration of a direct effect of ethanol on cultured granulosa-lutein cells and suggest that ethanol may inhibit action of LH on the corpus luteum. A direct selective toxic effect of EtOH on the ovary may be responsible for some of the reproductive abnormalities observed in alcoholic women.     

The reinforcing properties of salsolinol in the ventral tegmental area: evidence for regional heterogeneity and the involvement of serotonin and dopamine

Background:  Salsolinol (SAL), the condensation product of acetaldehyde and dopamine, may be a factor contributing to alcohol abuse. Previous research indicated that both ethanol and acetaldehyde are self-administered into the posterior ventral tegmental area (VTA). The current study examined SAL self-infusions into the VTA, and determined the involvement of dopamine neurons and 5-HT₃ receptors in this process.
Methods:  The intracranial self-administration technique was used to determine the self-infusion of SAL into the VTA of adult, male Wistar rats. The rats were placed in 2-lever (active and inactive) experimental chambers, and allowed to respond for the self-infusion of 0, 0.03, 0.1, 0.3, 1.0 or 3.0 μM SAL into the posterior or anterior VTA. In a second experiment, rats self-administered 0.3 μM SAL for the initial 4 sessions, co-administered SAL with ICS-205,930 (a 5-HT₃ receptor antagonist) or quinpirole (a D_2,3 receptor agonist) for sessions 5 and 6, and then only 0.3 μM SAL for session 7.
Results:  Wistar rats, given 0.03 to 0.3 μM SAL, received more infusions per session than did the group given artificial cerebrospinal fluid (aCSF) alone (e.g., 41 infusions for 0.1 μM SAL versus 9 infusions for the aCSF group), and responded more on the active than inactive lever. These effects were observed in the posterior but not in anterior VTA. Co-infusion of 100 μM ICS-205,930, or quinpirole significantly reduced self-infusions and active lever responding.
Conclusions:  SAL produces reinforcing effects in the posterior VTA of Wistar rats, and these effects are mediated by activation of DA neurons and local 5-HT₃ receptors.     

Comparison of vildagliptin and thiazolidinedione as add-on therapy in patients inadequately controlled with metformin: results of the GALIANT trial – a primary care, type 2 diabetes study

Aim: To assess the efficacy and tolerability of vildagliptin compared with thiazolidinediones (TZDs) as an add on to metformin treatment in a primary care patient population with type 2 diabetes.
Methods: This was a randomized, 12-week, open-label study comparing vildagliptin (100 mg, n = 1653) and TZD (agent and dose at the investigators' discretion, n = 825) add-on therapy in patients inadequately controlled [haemoglobin A_1C (HbA_1c): 7–10%] on a stable dose of metformin (≥1000 mg/day). The primary objective was to test non-inferiority of vildagliptin to TZDs for the difference in change in HbA_1c from baseline [established if the upper limit of the two-sided 95% confidence intervals (CI) did not exceed 0.4%].
Results: Mean (± s.e.) change in HbA_1c from baseline to study endpoint was –0.68 ± 0.02% in the vildagliptin group and −0.57 ± 0.03% in the TZD group. The difference between groups was −0.11% (95% CI: −0.17% and −0.04%), establishing the non-inferiority of vildagliptin (p = 0.001) after 3 months of treatment. Vildagliptin was non-inferior to TZDs for subgroups of race, age and body mass index. Body weight increased in the TZD group (0.33 ± 0.11 kg) and decreased in the vildagliptin group (mean: −0.58 ± 0.09 kg; p < 0.001 for difference). Adverse events occurred in similar proportions of patients in both groups (vildagliptin: 39.5% and TZD: 36.3%) Hypoglycaemia and abnormal changes in liver enzymes were uncommon.
Conclusions: This short-term study suggests that vildagliptin is as effective as TZDs after 3-month treatment as an add-on to metformin in a primary care population that included diverse patient subgroups.