Effect Of Sibutramine Research Articles

Sibutramine Effects on the Reproductive Performance of Pregnant Overweight and Non-Overweight rats

It is well established that sibutramine produces weight loss and is used frequently in women of childbearing age. However, the potential adverse consequences attributed to sibutramine use by women who may become pregnant is not known. It was thus of interest to determine the effects of sibutramine on the reproductive performance of pregnant rats. Overweight as well as non-overweight female Wistar rats were treated with sibutramine (6 mg/kg) orally, daily for 15 d and then mated with normal male rats. Pregnancy was confirmed and treatment continued with sibutramine until d 14 of pregnancy. On d 20 of pregnancy all rats were anesthetized for determination of various maternal and fetal parameters. There was a significant maternal weight reduction at the end of pregnancy in the non-overweight drug-treated group compared to the control (non-overweight, no drug). Sibutramine alone and overweight condition alone produced a significant increase in postimplantation loss and placental index. In the overweight with or without sibutramine groups a significant decrease in fetal weight was noted. Data suggest that sibutramine alone or the condition of excess weight in the absence of drugs produced impaired reproductive performance. However, treatment of overweight rats with sibutramine did not further exacerbate fetal loss compared to sibutramine alone or the effects noted with excess weight alone.

Effect of the Common -866G/A Polymorphism of the Uncoupling Protein 2 Gene on Weight Loss and Body Composition under Sibutramine Therapy in an Obese Taiwanese Population

Sibutramine, a serotonin and norepinephrine reuptake inhibitor, is used as an anti-obesity drug. Several pharmacogenetic studies have shown correlations between sibutramine effects and genetic variants, such as the 825C/T (rs5443) single nucleotide polymorphism (SNP) in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene. In this study, our goal was to investigate whether a common SNP, -866G/A (rs659366), in the uncoupling protein 2 (UCP2) gene could influence weight reduction and body composition under sibutramine therapy in an obese Taiwanese population. The study included 131 obese patients, 44 in the placebo group and 87 in the sibutramine group. We assessed the measures of weight loss and body fat reduction at the end of a 12-week treatment period by analysis of covariance (ANCOVA) models using gender, baseline weight, and body fat percentage at baseline as covariates. By comparing the placebo and sibutramine groups with ANCOVA, our data showed a strong effect of sibutramine on weight loss in the combined UCP2 -866 AA + GA genotype groups (p < 0.001). Similarly, a strong effect of sibutramine on body fat percentage loss was found for individuals with the AA or GA genotypes (p < 0.001). In contrast, sibutramine had no significant effect on weight loss (p = 0.063) or body fat percentage loss (p = 0.194) for individuals with the wild-type GG genotype, compared with the placebo group of the same genotype. Moreover, a potential gene-gene interaction between UCP2 and GNB3 was identified by multiple linear regression models for the weight loss (p < 0.001) and for the percent fat loss (p = 0.031) in response to sibutramine. The results suggest that the UCP2 gene may contribute to weight loss and fat change in response to sibutramine therapy in obese Taiwanese patients.

Differential effects of monoamine reuptake inhibitors on food intake and energy expenditure in a mouse model of diet‐induced obesity

Dopamine (DA), norepinephrine (NE) and serotonin (5‐HT) modulate feeding behavior and energy homeostasis. Here, we investigated effects of sibutramine (Sib), duloxetine (Dlx), and atomoxetine (Atx) on acute food intake (FI), daily FI and body weight (BW) gain over 28 d in diet‐induced obese (DIO) mice. Sib is a balanced reuptake inhibitor at transporters for DA (DAT), 5‐HT (SERT) and NE (NET), whereas Dlx and Atx are selective for SERT and NET, respectively. Mice, fed a high fat diet for 12 wk, weighed 40–44 g prior to receiving chronic twice daily oral dosing for 28 d. FI, BW, serum leptin levels and weight of adipose tissue were measured and compared to free concentrations of compounds in serum and brain. Sib (1–10 mg/kg), Dlx (3–30 mg/kg) and Atx (3–30 mg/kg) dose‐dependently decreased food intake 4 and 8 hr after a single dose (hypophagia rank order of potency: Sib = Dlx &gt; Atx). From 7 – 28 d, daily FI was equivalent in all groups of mice. At the highest doses tested, BW decreased significantly in Sib‐ and Atx‐treated mice at day 28 (~10% compared to vehicle), whereas BW was unchanged by the end of chronic Dlx treatment. On day 29, all compounds decreased serum leptin levels. Atx‐induced decrease in BW was accompanied by a reduction in total brown adipose tissue. These results suggest that the balance of activity at DAT, SERT and NET differentially influences acute hypophagia, energy expenditure and sustained weight loss.

Variegate porphyria in a 46‐year‐old patient taking sibutramine for weight loss

The acute hepatic porphyrias can cause life-threatening attacks of neurovisceral symptoms that mimic other acute medical conditions. Variegate porphyria caused by mutations in the protoporphyrinogen oxidase (PPOX) gene is a latent disorder characterized by exacerbations induced by fasting, alcohol consumption or certain drugs. We describe the case of a 46-year-old female patient presenting with a first episode of symptomatic porphyria after 10 d of sibutramine treatment for weight loss. Genetic analysis showed a heterozygous R168H hot spot mutation in the PPOX gene. A putative effect of sibutramine on the hepatic haem biosynthetic pathway and reduced food intake have likely caused this exacerbation of a porphyria attack. Although this may be the first case report of this kind, the risk of acute porphyria should be considered in patients using pharmacotherapy for obesity.

The weight lowering effect of sibutramine and its impact on serum lipids in cardiovascular high risk patients with and without type 2 diabetes mellitus - an analysis from the SCOUT lead-in period.

BackgroundObesity, type 2 diabetes mellitus (T2D) and unhealthy blood lipid profile are strongly associated with the risk of developing cardiovascular disease (CVD). We examined whether blood lipid changes with short term administration of the weight lowering drug, sibutramine and lifestyle modification in obese and overweight high-risk patients was associated with T2D status at screening.MethodsThe Sibutramine Cardiovascular OUTcomes (SCOUT) trial included obese and overweight patients at increased risk of cardiovascular events. All patients received guidance on diet and exercise plus once-daily 10 mg sibutramine during the 6-week, single blind lead-in period. Multivariable regression models were used to investigate factors associated with changes in lipid levels during the first four weeks of treatment.ResultsA total of 10 742 patients received at least one dose of sibutramine during the 6-week lead-in period of SCOUT. After four weeks, patients experienced mean reductions in low density lipoprotein (LDL-C) 0.19 mmol/L, high density lipoprotein (HDL-C) 0.019 mmol/L, very low density lipoprotein (VLDL-C) 0.08 mmol/L, total cholesterol (TC) 0.31 mmol/L and triglycerides 0.24 mmol/L (p < 0.0001 for each). Four week changes in LDL-C, HDL-C and total cholesterol for patients without vs. with T2D were: LDL-C:-0.25 mmol/L vs. -0.18 mmol/L, P = 0.0004; HDL-C: -0.03 mmol/L vs. -0.02 mmol/L, P = 0.0014; total cholesterol: -0.37 mmol/l vs. -0.29 mmol/l, P = 0.0009. Multivariable regression analysis showed that similar decreases in body mass index (BMI) affected lipid changes differently according to diabetes status. A 1 kg/m2 decrease in BMI in patients with T2D was associated with -0.09 mmol/L in LDL-C (P < 0.0001) and -0.01 mmol/L in HDL-C (P = 0.0001) but larger changes of -0.16 mmol/L LDL-C and -0.03 mmol/L in HDL-C (P < 0.0001 for both) in patients without T2D.ConclusionShort term weight management with sibutramine therapy in obese or overweight high-risk patients induced significant mean reductions for all lipids. Those without T2D benefited most. Patients with hyperlipidaemia and the less obese patients also had greater falls in LDL-C and TC during weight loss. The trial is registered at ClinicalTrial.gov number: NCT00234832.

An obesity drug sibutramine reduces brain natriuretic peptide (BNP) levels in severely obese patients

Sibutramine is a selective inhibitor of the reuptake of monoamines. Plasma levels of brain natriuretic peptide (BNP) appear to be inversely associated with body mass index (BMI) in subjects with and without heart failure for reasons that remain unexplained. The aim of this study was to investigate the possible influence of sibutramine treatment on BNP levels in severely obese patients. Fifty-two severely obese female patients with BMI > 40 kg/m(2) were included to this study. The women were recommended to follow a weight-reducing daily diet of 25 kcal/kg of ideal body weight. During the treatment period, all patients were to receive 15 mg of sibutramine once a day. Blood chemistry tests were performed before the onset of the medication and after 12 weeks of treatment. None of the subjects was withdrawn from the study because of the adverse effects of sibutramine. Body weight (108.8 +/- 13.3 kg vs. 101.7 +/- 15.6 kg, p < 0.001), BMI (44.6 +/- 4.6 kg/m(2) vs. 41.8 +/- 5.7 kg/m(2), p < 0.001) and BNP [8.6 (0.5-49.5) ng/l vs. 3.1 (0.2-28.6) ng/l, p = 0.018] levels were significantly decreased after 12 weeks of sibutramine treatment. Total cholesterol (5.19 +/- 0.90 mmol/l vs. 4.82 +/- 1.05 mmol/l respectively; p < 0.001), low-density lipoprotein-cholesterol (3.26 +/- 0.86 mmol/l vs. 2.99 +/- 0.40 mmol/l respectively; p = 0.008), levels were significantly decreased; however, there was no significant alteration in high-density lipoprotein-cholesterol and triglyceride levels. This study has shown a decrease in BNP levels which may lead to improvement in cardiac outcome after sibutramine treatment. Further randomised studies are needed to be conducted to clarify the relationship between sibutramine and BNP.

Enantioselective pharmacokinetics of sibutramine in rat

Racemic sibutramine is widely used to treat obesity owing to its inhibition of serotonin and noradrenaline reuptake in synapses. Although the enantioselective effects of sibutramine and its two active desmethyl-metabolites, monodesmethylsibutramine (MDS) and didesmethylsibutramine (DDS), on anorexia and energy expenditure have been elucidated, the enantioselective pharmacokinetics of sibutramine are still unclear. Therefore, we aimed to characterize the enantioselective pharmacokinetics of sibutramine and its metabolites in plasma and urine following an intravenous and a single oral administration of sibutramine in rats. The absolute bioavailability of sibutramine was only about 7%. The pharmacologically less effective S-isomer of DDS was predominant in the plasma: the C ( max ) and the AUC ( inf ) were 28 and 30 times higher than those of the R-isomer, respectively (p<0.001). In the urine, the concentrations of the R-isomers of hydroxylated DDS and hydroxylated and carbamoylglucuronized MDS and DDS appeared to be 11.3-, 5.1-, and 5.3-times the concentrations of the respective S-isomers. Thus, regardless of increased potency than the S-enantiomers, the R-enantiomers of the sibutramine metabolites MDS and DDS were present at lower concentrations, owing to their rapid biotransformation to hydroxylated and/or carbamoylglucuronized forms and their faster excretion in the urine. The present study is the first to elucidate the enantioselective pharmacokinetics of sibutramine in rats.

Metformin for weight reduction in non-diabetic patients on antipsychotic drugs: a systematic review and meta-analysis

Weight gain is a clinically important side effect of antipsychotic drug therapy. The aim of this study was to determine the effect of the antidiabetic drug metformin on antipsychotic-induced weight gain in non-diabetic patients. In a systematic literature review we identified 195 citations from which seven randomized, placebo-controlled studies (398 patients) were included in the final analysis. Studies in adults (n = 5) and in children (n = 2) were analysed separately. Compared with placebo, metformin treatment caused a significant body weight reduction in adult non-diabetic patients treated with atypical antipsychotics (4.8%, 95% CI 1.6 to 8.0) and in children (4.1%, 95% CI 2.2 to 6.0). There was evidence of substantial heterogeneity among studies, and when the analysis was restricted to patients with a manifest (>10%) body weight increase prior to randomisation metformin reduced weight by 7.5% (95% CI 2.9 to 12.0). The effect was larger in Asians (7.8%, 95% CI 4.4 to 11.2) than in Hispanics (2.0%, 95% CI 0.7 to 3.3). In conclusion, metformin has a pronounced weight-reducing effect in antipsychotic-treated patients, especially in those with a manifest weight gain. Although direct comparisons are lacking, the observed effect on body weight compares favourably with the effect of sibutramine and orlistat, approved for weight reduction. However, metformin is not approved for use in non-diabetic patients and it is still not generally advisable to recommend metformin to counteract antipsychotic-induced weight gain.

Comparison of the effects of sibutramine versus sibutramine plus metformin in obese women

Sibutramine and metformin are drugs commonly used to obtain weight loss. We aimed to compare the effects of sibutramine alone with that of sibutramine plus metformin combination on weight loss, insulin sensitivity, leptin and C reactive protein in obese women. Seventy obese women were included. After a diet period of month (baseline), each individual was randomly assigned to receive 15 mg sibutramine (sibutramine group; n = 36) or 15 mg sibutramine plus 1,700 mg metformin per day (sibutramine plus metformin group; n = 34) during the next 12 months. Body weight, insulin resistance by the homeostasis model assessment model (HOMA-IR), leptin and C reactive protein were measured at baseline, after 3 months and after 12 months. Mean weight losses in sibutramine and sibutramine plus metformin groups were 5.3 +/- 4.0% (P < 0.001) and 6.8 +/- 3.9% (P < 0.001) after 3 months, and 10.5 +/- 4.4% (P < 0.001) and 15.7 +/- 4.6% (P = 0.007) after 12 months, respectively. HOMA-IR value also decreased in both sibutramine (P = 0.045 and P = 0.002) and sibutramine plus metformin groups (P = 0.04 and P = 0.015) after 3 and 12 months, respectively. Similarly, serum leptin levels decreased in both sibutramine (P = 0.04, P = 0.01) and sibutramine plus metformin groups (P = 0.023, P = 0.025) after 3 and 12 months, respectively. There was also significant reductions in serum C reactive protein levels in both sibutramine (P = 0.045, P = 0.02) and sibutramine plus metformin groups (P = 0.007, P = 0.001) after 3 and 12 months, respectively. These decrements of body weight, HOMA-IR, serum leptin and C reactive protein levels were not statistical significance between these two groups both after 3 and 12 months (P > 0.05). Combination of sibutramine with metformin did not result in any further effects on weight loss, insulin resistance, leptin and C reactive protein levels when compared to sibutramine alone.

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Weight loss and body fat reduction under sibutramine therapy in obesity with the C825T polymorphism in the GNB3 gene

The relationship between weight reduction after sibutramine treatment and a single nucleotide polymorphism, rs5443 (C825T), in the guanine nucleotide binding protein beta polypeptide 3 (GNB3) gene is currently inconsistent. In this study, we aimed to reassess whether the GNB3 rs5443 single nucleotide polymorphism could influence weight reduction and body composition change under sibutramine therapy in 131 obese Taiwanese patients. By comparing the sibutramine and placebo groups with analysis of covariance, our data showed a strong effect of sibutramine on weight reduction (7.4+/-1.4 vs. 3.4+/-1.2 kg; P<0.001) and on body fat percentage loss (4.2+/-0.1 vs. 2.1+/-0.1%; P<0.001) in the combined TT+TC carriers. In contrast, sibutramine caused no significant additional effect on weight loss (P = 0.078) or on body fat percentage loss (P = 0.441) in homozygous C allele carriers.

Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility

Sibutramine is an inhibitor of norepinephrine and 5-HT reuptake largely used in the management of obesity. Although a fairly safe drug, postmarketing adverse effects of sibutramine were reported including abnormal ejaculation in men. This study investigates the effects of sibutramine on ejaculation and vas deferens and seminal vesicle contractility. Adult male rats received sibutramine (5; 20; or 50 mg kg − 1 , ip) and after 60 min were exposed to receptive females for determination of ejaculation parameters. The vasa deferentia and seminal vesicles of untreated rats were mounted in isolated organ baths for recording of isometric contractions and HEK293 cells loaded with fluorescent calcium indicator were used to measure intracellular Ca 2+ transients. Sibutramine 5 and 20 mg kg − 1 reduced ejaculation latency whereas 50 mg kg − 1 increased ejaculation latency. Sibutramine 3 to 30 μM greatly increased the sensitivity of the seminal vesicle and vas deferens to norepinephrine, but at concentrations higher than 10 μM there were striking depressions of maximal contractions induced by norepinephrine, carbachol and CaCl 2. In HEK293 cells, sibutramine 10 to 100 μM inhibited intracellular Ca 2+ transients induced by carbachol. Depending on the doses, sibutramine either facilitates or inhibits ejaculation. Apart from its actions in the central nervous system, facilitation of ejaculation may result from augmented sensitivity of smooth muscles to norepinephrine while reductions of intracellular Ca 2+ may be involved in the delayed ejaculation observed with high doses of sibutramine.

5‐HT1A Activation Counteracts Cardiovascular But Not Hypophagic Effects of Sibutramine in Rats

The noradrenaline (NA) and serotonin reuptake inhibitor, sibutramine, gives effective weight loss, but full efficacy cannot be attained at approved doses due to cardiovascular side effects. We assessed in rats the contributions of NA and serotonin transporters to sibutramine's hypophagic and cardiovascular effects, and whether selective 5-hydroxytryptamine (5-HT(1A)) receptor activation could counteract the latter without affecting the former. Food intake was assessed in freely feeding rats and cardiovascular parameters in conscious telemetered rats. Ex vivo radioligand binding was used to estimate brain monoamine transporter occupancy. Sibutramine (1-10 mg/kg p.o.) dose-dependently reduced food intake; however, 10 mg/kg p.o. markedly elevated blood pressure and heart rate. Sibutramine gave greater occupancy of NA than serotonin reuptake sites. Coadministration of the selective 5-HT(1A) agonist F-11440 (2.5 mg/kg p.o.) attenuated sibutramine-induced hypertension and tachycardia without altering its food intake effects. The selective NA reuptake inhibitors, nisoxetine or reboxetine, did not alter food intake alone, but each reduced food intake when combined with F-11440. These results suggest that sibutramine-induced hypophagic and cardiovascular effects are largely due to increased brain synaptic NA via NA reuptake inhibition, and that 5-HT(1A) activation can counter the undesirable cardiovascular effects resulting from increased sympathetic activity. Selective NA reuptake inhibitors did not reduce food intake alone but did when combined with 5-HT(1A) activation. Hence increased synaptic serotonin, via serotonin reuptake inhibition or 5-HT(1A) activation, together with increased NA, would appear to produce hypophagia. Thus weight loss with minimal cardiovascular risk could be achieved by 5-HT(1A) activation combined with NA transporter blockade.

Serum adiponectin and resistin in rats under three isocaloric diets: The effect of sibutramine

The aim of the study was to investigate the effects of (1) macronutrients on food intake, body composition and serum resistin and adiponectin and (2) sibutramine(S) on the above parameters in rats fed with isocaloric diets. Three groups of male Wistar rats ( n = 63) were fed with high fat diet (HFD), high carbohydrate diet (HCD) or high protein diet (HPD) for 13 weeks. In the last 3 weeks each group was divided into three subgroups and received S 5 mg/kg or 10 mg/kg, or vehicle. Body weight was measured weekly, gastrocnemius muscle, perirenal, retroperitoneal and epididymal fat were isolated, fat/lean ratio was calculated and serum adiponectin and resistin were assayed. S did not affect lean body mass in any group. HFD was associated with elevated fat/lean ratio regardless of S administration. S at 10 mg/Kg decreased fat/lean ratio in the HCD and HPD and adiponectin in the HFD group. S did not affect resistin in any group. Adiponectin was paradoxically elevated in the HFDS10 compared to the HCD or HPD S10 groups. Resistin was lower in the HCD compared to the HPD and HFD groups. Results suggest a preferential effect of S on body fat. The detrimental effect of S on adiponectin can be attributed to its sympathomimetic properties. Adiponectin was paradoxically elevated in the HFD and resistin in the HPD group, results that require further investigation.

Effect of Sibutramine on Na+, K+ATPase Activity and Tryptophan Levels on Male and Female Rat Brain

Some drugs that are clinically used in weight control, like sibutramine, act on the serotonergic metabolism, but its relation with free radical (FR) production in the CNS is still unknown. The aim of the work was to evaluate the effect of sibutramine on FR production. Female and male Wistar rats (250 g weight) were used; the animals received sibutramine (10 mg/kg each 36 hours) intraperitoneally during 15 days. At the end of the study, the rats were sacrificed and their brains used to measure lipid peroxidation (TBARS), Na+, K+ ATPase activity, reduced glutathione (GSH), and tryptophan (TRP) levels, by means of validated methods. The activity of Na+, K+ATPase and total ATPase was increased in males and decreased in females. GSH concentration was increased and the levels of TBARS decreased by an effect related to sibutramine in the female group. Sibutramine decreased TRP concentration in the female group, but increased it in the male one, with respect to the control group. Our results suggest that sibutramine produce an antioxidant effect stimulated by the endogenously produced tryptophan and it protects the fluidity of plasma membrane in rat brain.

A preclinical model of binge eating elicited by yo-yo dieting and stressful exposure to food: effect of sibutramine, fluoxetine, topiramate, and midazolam

Preclinical models are needed to investigate the neurobiology and psychobiology of binge eating and to identify innovative pharmacotherapeutic strategies. A modification of the model based on the combination of cyclic caloric restrictions and acute stress was developed to further increase its face validity and reliability and, for the first time, to assess its predictive value. Four groups of female rats were employed: group 1 was normally fed and not stressed on the test day (25th); group 2 was fed normally but was exposed to an acute stress on day 25; group 3 was exposed to three cycles (4 days 66% of chow intake + 4 days food ad libitum) of yo-yo dieting but not stressed; and group 4 was exposed to cyclic yo-yo dieting and then stressed. All groups were fed highly palatable food (HPF) for 2 h on days 5-6 and 13-14. Acute stress was elicited by exposing rats to HPF, but preventing them from access to it for 15 min. The combination of cyclic food restriction and stressful exposure to food markedly increased HPF intake. Sibutramine and fluoxetine inhibited food intake in all conditions. Topiramate selectively inhibited compulsive HPF intake in rats submitted to caloric restriction and stress. Midazolam increased HPF intake. Pharmacological results suggest that this model, in addition to face validity as an isomorphic model of human binge eating, is endowed with good predictive validity.

Effect of sibutramine in combination with L-carnitine in comparison with sibutramine as monotherapy on adiposity and insulin sensitivity in obese women

| 273 Employee: J. Liu and R. Spanheimer are employees of Takeda Pharmaceuticals North America. M. Raanan and A. Perez are employees of Takeda Global Research & Development Center, Inc.

Effect of sibutramine on weight reduction in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial

Effect of sibutramine on weight reduction in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial

Effect of Sibutramine on Weight Reduction in Women With Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Weight reduction, although often difficult to achieve, has been the major target for intervention in obese women with polycystic ovary syndrome (PCOS). Metformin does have salutary effects in these patients, but its value as a weight-reducing agent remains in doubt. This prospective, double-blind, placebo-controlled, multicenter trial evaluated sibutramine, a Food and Drug Administration-approved anti-obesity drug that inhibits the reuptake of serotonin and norepinephrine, thereby increasing satiety and adrenergic activity. Forty-two patients aged 18 to 40 years with confirmed PCOS and a body mass index (BMI) exceeding 27 kg/m2 were entered into the study, and 34 completed it. Participants received either 15 mg of sibutramine daily or a placebo. In addition, all patients received advice about diet and physical activity. After 6 months, patients given sibutramine had lost 7.8 kg of body weight on average, compared with 2.8 mg for placebo patients. The superiority of sibutramine became statistically significant by week 2. Similar results were obtained for BMI. Both waist and hip circumference decreased in sibutramine-treated patients, but waist/hip ratios were similar in the actively treated and placebo groups. Both sibutramine and placebo were associated with an increased number of menstrual periods. Sibutramine treatment correlated with significant reductions in levels of apolipoprotein B, the apolipoprotein B/apolipoprotein A ratio, triglycerides, and cystatin C. Sibutramine, when combined with lifestyle interventions, can lead to significant weight reduction in obese women with PCOS. In addition, it seems to have positive effects on metabolic and cardiovascular risk factors.

The Effects of Medications Used for the Management of Diabetes and Obesity on Postprandial Lipid Metabolism

Postprandial lipemia has emerged as an independent risk factor for coronary artery disease. In this systematic review we examined the effect of the medications used for the management of diabetes, obesity and dyslipidemia on postprandial lipemia. It should be mentioned that no standardization exists for a test meal and for the duration of observation postprandially to allow for direct comparisons between the published studies. Type 2 diabetes mellitus and insulin resistance are associated with enhanced postprandial lipemia. Insulin is effective in reducing both fasting and post prandial total triglyceride levels as well as triglycerides contained in the triglyceride-rich lipoprotein sub-fractions. Additionally, the newer rapid-acting insulin analogues seem to be more effective in the reduction of postprandial lipemia than the short-acting human insulins. Acarbose ameliorates postprandial lipemia and reduces the atherogenic chylomicron and very low density lipoprotein remnants. Metformin reduces both fasting and postprandial triglyceridemia, fasting and post-prandial free fatty acids and may increase the concentrations of the high density lipoprotein cholesterol. Sulfonylureas reduce fasting and postprandial triglyceride levels while data on the effect on high density lipoprotein levels are inconsistent. The effect of meglitinides on postprandial lipid metabolism is neutral. Rosiglitazone decreases fasting and postprandial free fatty acids but has no significant effect on fasting and postprandial triglycerides. Pioglitazone has additional beneficial effects on lipid metabolism because it reduces postprandial free fatty acids, fasting and postprandial triglycerides and increases high density lipoprotein cholesterol levels. Limited available data suggest that glucagon-like peptide-1 analogues and vildagliptin reduce postprandial lipemia through reduction of intestinally-derived triglycerides. No data exist on the effect of sitagliptin on postprandial lipemia. Orlistat improves postprandial lipemia by reducing the absorption of the dietary fat; no data exist on the effect of sibutramine and rimonabant on the metabolism of lipids in the postprandial state.