Evaluation of the food effect on a drospirenone only contraceptive containing 4 mg administered with and without high-fat breakfast in a randomised trial.

BACKGROUND: The objective of the present trial was to assess the difference in pharmacokinetics (PK) of an oral test preparation containing 4 mg drospirenone (DRSP) under fasting conditions compared to PK upon food intake after single dose administration. METHODS: Open label, single centre, two-treatment, two-sequence, crossover study in 24 healthy female volunteers, with duration of 1 day per sequence and with a real wash-out period of 14 days to investigate the relative bioavailability of DRSP with both forms of administration. The 90% confidence intervals (CI) were calculated for the intra-individual ratio (test with food vs. without food) of the PK endpoints Area under the curve; 0-72 h [AUC(0-72 h)] and maximal plasma concentration [Cmax] of DRSP. RESULTS: The 90% CI calculated by analysis of variance using logistic transformation (ANOVA-log) for the endpoint, intra-individual ratio (Test 'A' = with food intake) vs. Test 'B' = without food intake) of AUC(0-72 h) of drospirenone was between 104.72 and 111.36%. The 90% CI calculated by means of ANOVA- log for the endpoint intra-individual ratio (Test 'A' vs. Test 'B') of Cmax of DRSP was between 118.58 and 141.10%. The mean relative bioavailability of the test with food 'A' compared to the Test without food 'B' after single dose administration based on the endpoints AUC(0-72 h) was 107.99%; for the endpoint Cmax it was 129.35%. CONCLUSIONS: The rate of absorption, based on the endpoint Cmax of DRSP was increased by about 30% under fed conditions. With respect to consumer habits, this may represent a relevant benefit for contraceptive safety, as the time span between food consumption and pill intake does not play a role. IMPLICATIONS: Our results suggest that the food intake has no impact on the absorption of 4 mg DRSP in the management of contraception. This increases the contraceptive efficacy as no interference with food is expected when consuming the oral formulation under real life conditions. TRAIL REGISTRATION: Trial registration number: EudraCT-No: 2012-004,309-28.

Whey Protein Drink Ingestion before Breakfast Suppressed Energy Intake at Breakfast and Lunch, but Not during Dinner, and Was Less Suppressed in Healthy Older than Younger Men.

Ageing is associated with changes in feeding behavior. We have reported that there is suppression of energy intake three hours after whey protein drink ingestion in young, but not older, men. This study aimed to determine these effects over a time period of 9 h. Fifteen younger (27 ± 1 years, 25.8 ± 0.7 kg/m2) and 15 older (75 ± 2 years, 26.6 ± 0.8 kg/m2) healthy men were studied on three occasions on which they received, in a randomized order, a 30 g/120 kcal, 70 g/280 kcal whey-protein, or control (~2 kcal) drink. Ad-libitum energy intake (sum of breakfast, lunch, and dinner) was suppressed in a protein load responsive fashion (P = 0.001). Suppression was minimal at breakfast, substantial at lunch (~-16%, P = 0.001), no longer present by dinner, and was less in older than younger men (-3 ± 4% vs. -8 ± 4%, P = 0.027). Cumulative protein intake was increased in the younger and older men (+20% and +42%, P < 0.001). Visual analogue scale ratings of fullness were higher and desire to eat and prospective food consumption were lower after protein vs. control, and these effects were smaller in older vs. younger men (interaction effect P < 0.05). These findings support the use of whey-protein drink supplements in older people who aim to increase their protein intake without decreasing their overall energy intake.

Switching from glargine+insulin aspart to glargine+insulin aspart 30 before breakfast combined with exercise after dinner and dividing meals for the treatment of type 2 diabetes patients with poor glucose control - a prospective cohort study.

BACKGROUND: This study aimed to examine the switch from glargine+once daily insulin aspart (1 + 1 regimen) to glargine+insulin aspart 30 before breakfast combined with exercise and in patients with type 2 diabetes mellitus (T2DM) with poorly controlled blood glucose levels. METHODS: Consecutive patients with poorly controlled T2DM (n = 182) were switched from the 1 + 1 regimen to glargine+insulin aspart 30 before breakfast in combination with exercise after dinner and dividing meals in two (same final calories intake). The insulin doses were adjusted according to blood glucose levels within 4 weeks after the switch and maintained for 12 weeks. Fasting blood glucose (FBG), 2-hpostprandial glucose (2hPG), glycosylated hemoglobin (HbA1c), body mass index (BMI), daily insulin dose, and hypoglycemia events were assessed. RESULTS: Sixteen weeks after the switch, 2 h PG levels and HbA1c levels (from 8.5 to 7.4%, P = 0.001) were improved. The proportions of patients reaching the HbA1c targets of 7.5% were improved (from 22.5 to 58.7%, P = 0.001). Among the 182 patients, 24 (13.2%) divided one meal into two meals, and 23 (12.6%) divided two meals into four meals. Among all patients, 8.5% had to reuse insulin aspart before dinner after the study. One patient with diarrhea and poor appetite experienced severe hypoglycemia. The rate of hypoglycemia was 3.76 events/patient-year. The daily insulin Aspart 30 dose was higher than the original insulin aspart dose (P = 0.001). CONCLUSIONS: For patients with poorly controlled T2DM under the 1 + 1 regimen, switching to glargine+insulin aspart 30 before breakfast combined with exercise after dinner and dividing meals showed promising benefits.

Caffeine Transiently Affects Food Intake at Breakfast.

BACKGROUND: Caffeine is frequently added to dietary supplements with claims it facilitates weight loss. OBJECTIVE: The purpose of this study was to test the hypothesis that caffeine administration reduces laboratory and free-living food intake by reducing appetite and that these effects vary by body mass index (BMI). PARTICIPANTS/SETTING: Fifty adults aged 18 to 50 years completed the study (42% male). Exclusion criteria included no previous experience with caffeine, previous adverse event following caffeine consumption, taking any medications or having a medical condition contraindicating caffeine or stimulant consumption or affecting appetite or eating, and reported tobacco use within the past 6 months. DESIGN AND INTERVENTION: Participants visited the laboratory on four separate occasions to complete a double-blind, placebo-controlled, randomized, crossover study. On the first three visits, participants consumed a beverage containing 0, 1, or 3 mg/kg caffeine (order randomized). Thirty minutes later, participants consumed a buffet breakfast, ad libitum. After leaving the laboratory, participants completed hourly appetite assessments and dietary habit books until midnight or bedtime. The fourth session consisted of questionnaires, debriefing, and compensation. MAIN OUTCOME MEASURES: Total and macronutrient intake and appetite sensations in and out of the laboratory were measured. STATISTICAL ANALYSES PERFORMED: Intake data were analyzed using mixed analysis of covariance (ANCOVA). Appetite sensations were analyzed using repeated measures mixed ANCOVA. RESULTS: Total laboratory energy intake was lower (∼10%) after 1 mg/kg caffeine (650.4±52.2 kcal at 1 mg/kg; 721.2±63.2 at 0 mg/kg; 714.7±79.0 at 3 mg/kg) (P=0.046). In the laboratory, appetite sensations were not significantly different by caffeine treatment. Out of the laboratory, neither total intake nor appetite was significantly different by caffeine treatment. There were no significant interactions between caffeine treatment and BMI on intake and appetite sensations in or out of the laboratory. CONCLUSIONS: These results suggest caffeine has weak, transient effects on energy intake and do not support caffeine as an effective appetite suppressant.

Shift from Levothyroxine Tablets to Liquid Formulation at Breakfast Improves Quality of Life of Hypothyroid Patients.

BACKGROUND: Until recently, treatment of hypothyroidism has been accomplished using monotherapy of synthetic L-thyroxine (L-T4) sodium tablets that should be taken 30-60 minutes before breakfast. Nowadays, a liquid preparation of levothyroxine is available and can effectively replace tablets without the need of waiting before having breakfast. Evidence of Quality of life (QoL) improvement when shifting from the former to the latter preparation, however, is still lacking. OBJECTIVE: The study aimed to assess changes in QoL of hypothyroid patients dissatisfied with their therapy with L-T4 sodium tablets who were switched from tablets taken 30-60 minutes before breakfast to liquid L-T4 at breakfast. METHODS: A total of 418 consecutive hypothyroid subjects treated by means of L-T4 tablets were asked about their satisfaction/dissatisfaction in order to take the medication 30-60 minutes before having breakfast. Overall, 110 patients (26.3%) complained of the timing of their L-T4 therapy (30-60 minutes before breakfast). A dedicated QoL questionnaire (ThyTSQ), taking just a few minutes to be filled in was then administered to these dissatisfied patients. They were therefore switched to L-T4 to be taken at breakfast. Aiming to avoid TSH elevation due to L-T4 tablets malabsorption caused by meal interference and gastric pH changes, patients were invited to take L-T4 liquid form, as this is claimed to be scarcely affected by the non-fasting state. The questionnaire (ThyTSQ) was administered again at the control visit 3 months later. TSH, FT4, FT3 serum concentrations and metabolic parameters were also recorded. RESULTS: An improved QoL, mainly due to an easier adherence to treatment, was reported by 66.6% of 102 patients who completed the study after shifting from taking medication 30-60 minutes before breakfast to at breakfast ingestion (P<0.01). An overall 10.7% of patients found the liquid formulation distasteful. Mean values of TSH, FT4, FT3, and of metabolic parameters did not significantly change but in eight patients (7.7%) who showed a TSH increase > 2mIU/L. CONCLUSION: In hypothyroid subjects dissatisfied with L-T4 tablets ingested 30-60 minutes before breakfast, the shift to the same dose of L-T4 in liquid form taken at breakfast improved QoL in the majority of patients, without affecting thyroid function.

Potato protease inhibitor II suppresses postprandial appetite in healthy women: a randomized double-blind placebo-controlled trial.

The effect of potato protease inhibitor II (PI2) on postprandial appetite was examined in a randomized double-blind placebo-controlled cross-over trial involving 44 healthy women. In separate test sessions, participants consumed a capsule containing placebo or potato extract standardized to 15 or 30 mg PI2 after overnight fasting. One hour later, a standard 390 kcal breakfast was served. At regular time points during the three-hour period after breakfast, appetite was measured by visual analog scales, and blood samples were collected for assay of cholecystokinin, insulin, and glucose. Compared with the placebo, consumption of 15 mg or 30 mg PI2 one hour prior to a standard breakfast meal resulted in significantly lower postprandial hunger, desire to eat, and prospective consumption, as well as significantly higher postprandial fullness. Consumption of 15 mg PI2 also resulted in significantly higher postprandial plasma levels of cholecystokinin compared with the placebo. No significant main effect of treatment was found on insulin and glucose. No adverse events were reported. Results from the study revealed that consumption of potato PI2 at the examined doses was well tolerated, suppressed subjective appetite in a dose-dependent manner, and increased plasma concentrations of cholecystokinin. Future studies are needed to evaluate the long-term effect of PI2 on body weight.

Effects of polydextrose with breakfast or with a midmorning preload on food intake and other appetite-related parameters in healthy normal-weight and overweight females: An acute, randomized, double-blind, placebo-controlled, and crossover study.

Polydextrose (PDX) reduces subsequent energy intake (EI) when administered at midmorning in single-blind trials of primarily normal-weight men. However, it is unclear if this effect also occurs when PDX is given at breakfast time. Furthermore, for ecological validity, it is desirable to study a female population, including those at risk for obesity. We studied the effects of PDX, served as part of a breakfast or midmorning preload, on subsequent EI and other appetite-related parameters in healthy normal-weight and overweight females. Per earlier studies, the primary outcome was defined as the difference in subsequent EI when PDX was consumed at midmorning versus placebo. Thirty-two volunteers were enrolled in this acute, double-blind, placebo-controlled, randomized, and crossover trial to examine the effects of 12.5 g of PDX, administered as part of a breakfast or midmorning preload, on subsequent EI, subjective feelings of appetite, well-being, and mood. Gastric emptying rates and the blood concentrations of glucose, insulin, cholecystokinin, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide tyrosine-tyrosine were measured in the group that received PDX as part of their breakfast. There were no differences in EI between volunteers who were fed PDX and placebo. PDX intake with breakfast tended to elevate blood glucose (P = 0.06) during the postabsorptive phase, significantly lowered insulin by 15.7% (P = 0.04), and increased GLP-1 by 39.9% (P = 0.02); no other effects on blood parameters or gastric emptying rates were observed. PDX intake at midmorning reduced hunger by 31.4% during the satiation period (P = 0.02); all other subjective feelings of appetite were unaffected. Volunteers had a uniform mood profile during the study. PDX was well tolerated, causing one mild adverse event throughout the trial.

Equal improvement in glycaemia with lixisenatide given before breakfast or the main meal of the day.

AIMS: The aim of this study is to explore whether administration timing affects glycaemic control by lixisenatide once-daily in type 2 diabetes mellitus (T2DM). METHODS: A phase IIIb, open-label, 1:1 randomized, active-controlled, 24-week multicentre study of T2DM patients inadequately controlled on metformin was conducted. Patients were administered lixisenatide before breakfast or the main meal. The primary endpoint was change from baseline at week 24 in glycated haemoglobin (HbA1c). Other endpoints: changes in body weight, fasting plasma glucose (FPG), 7-point self-monitored plasma glucose (SMPG) and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) score. Adverse events (AEs) were monitored. RESULTS: Mean change in HbA1c from baseline at week 24 was -0.65% (-7.1mmol/mol; main meal) and -0.74% (-8.1mmol/mol; breakfast). Mean changes in FPG, body weight and DTSQs score were comparable between groups. The mean change in body weight (kg) was -2.60 (main meal) and -2.80 (breakfast group). The 7-point SMPG profiles showed greatest reductions in postprandial glucose after the meal at which lixisenatide was administered, with a residual effect seen on the subsequent meal. AE rates were similar between groups, including gastrointestinal AEs. CONCLUSIONS: Lixisenatide before the main meal was noninferior to lixisenatide before breakfast in patients insufficiently controlled on metformin. Lixisenatide treatment allows flexibility in administration timing.