Trial of a long-acting preparation of diethylpropion in obese diabetics. Obesity in diabetes. Some considerations on treatment. Latin-American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients. A randomized trial of sibutramine in the management of obese type 2 diabetic patients treated with metformin. Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study. Cimetidine reduces weight and improves metabolic control in overweight patients with type 2 diabetes. Health-related quality of life in a randomised placebo-controlled trial of sibutramine in obese patients with type II diabetes. Absence of cardiac valve dysfunction in obese patients treated with sibutramine. Fluoxetine therapy in obese diabetic and glucose intolerant patients. The effect of an anorectic agent (Mazindol) on control of obese diabetics. [Mazindol in the treatment of obese diabetic patients]. [Weight reduction in obese diabetics: a double-blind study of diethylpropionate (author's transl)]. Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study. The effects of orlistat on body weight and glycaemic control in overweight patients with type 2 diabetes: a randomized, placebo-controlled trial. A study of fluoxetine in obese elderly patients with type 2 diabetes. Role of sibutramine in the treatment of obese Type 2 diabetic patients receiving sulphonylurea therapy. Fluoxetine treatment of the obese diabetic. Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. Fluoxetine in the treatment of obese type 2 diabetic patients. One-year outcome of a combination of weight loss therapies for subjects with type 2 diabetes: a randomized trial. Double-blind clinical evaluation of mazindol (42-548) in obese diabetics. Weight control in obese diabetics. A comparative trial of Filon and phenmetrazine. Orlistat in hypertensive overweight/obese patients: results of a randomized clinical trial. [EXPERIENCES WITH THE THERAPEUTIC USE OF AN ANOREXIC SUBSTANCE ON DIABETES OF THE OBESE]. Clinical evaluation of sibutramine in obese type 2 diabetic patients refractory to dietary management. Clinical efficacy of orlistat therapy in overweight and obese patients with insulin-treated type 2 diabetes: A 1-year randomized controlled trial. Double blind clinical trial of mazindol on weight loss blood glucose, plasma insulin and serum lipids in overweight diabetic patients. Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study. Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes. A controlled trial of phentermine in obese diabetic patients. Effects of sibutramine in obese female subjects with type 2 diabetes and poor blood glucose control. Use of diethylpropion in obese diabetic patients.
nan nan To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat.
                Double-blind, parallel, randomized, placebo-controlled, multicentre study.
                Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline.
                After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low.
                Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile. To evaluate the effects of sibutramine (15 and 20 mg/day) on weight, metabolic control, and blood pressure in metformin-treated obese subjects with type 2 diabetes.
                A 12-month randomized prospective placebo-controlled double-blind study was performed. It included 21 primary and secondary care centers in England, Canada, France, and Belgium. A total of 195 subjects (44% male) with type 2 diabetes and a BMI >27 kg/m(2) were studied. Changes were assessed in weight, blood pressure and resting heart rate, HbA(1c), fasting glucose, and lipids.
                Sibutramine induced significant weight loss (P < 0.001) with both 15 mg/day (5.5 +/- 0.6 kg at 12 months) and 20 mg/day (8.0 +/- 0.9 kg), whereas placebo did not (0.2 +/- 0.5 kg). Weight loss > or = 10% was achieved by 14 and 27% of subjects receiving 15 and 20 mg, respectively, but by none given placebo. Glycemic control improved in parallel with weight loss, and subjects who lost > or = 10% weight showed significant decreases in both HbA(1c) (1.2 +/- 0.4%, P < 0.0001) and fasting plasma glucose (1.8 mmol/l, P < 0.001). HDL cholesterol increased slightly with the higher dose, whereas plasma triglycerides fell with both doses, especially in subjects with weight loss of > or = 10% (a 29% decrease, P < 0.01). Treatment was generally well tolerated. Sibutramine treatment raised sitting diastolic blood pressure by > or = 5 mmHg in a higher proportion of patients than did placebo (43% with 15 mg/day vs. 25% with placebo, P < 0.05), but this effect was less evident in subjects who had a weight loss of > or = 10% weight. Pulse rate increased significantly more with sibutramine, being > or = 10 bpm higher in 42% of treated patients versus 17% with placebo (P < 0.01).
                Sibutramine can be an effective adjunct to metformin treatment in selected obese type 2 diabetic subjects and improves metabolic control in individuals who lose weight. Obesity is an important risk factor for type 2 diabetes. Weight loss in patients with type 2 diabetes is associated with improved glycemic control and reduced cardiovascular disease risk factors, but weight loss is notably difficult to achieve and sustain with caloric restriction and exercise. The purpose of this study was to assess the impact of treatment with orlistat, a pancreatic lipase inhibitor, on weight loss, glycemic control, and serum lipid levels in obese patients with type 2 diabetes on sulfonylurea medications.
                In a multicenter 57-week randomized double-blind placebo-controlled study, 120 mg orlistat or placebo was administered orally three times a day with a mildly hypocaloric diet to 391 obese men and women with type 2 diabetes who were aged > 18 years, had a BMI of 28-40 kg/m2, and were clinically stable on oral sulfonylureas. Changes in body weight, glycemic control, lipid levels, and drug tolerability were measured.
                After 1 year of treatment, the orlistat group lost 6.2 +/- 0.45% (mean +/- SEM) of initial body weight vs. 4.3 +/- 0.49% in the placebo group (P < 0.001). Twice as many patients receiving orlistat (49 vs. 23%) lost > or = 5% of initial body weight (P < 0.001). Orlistat treatment plus diet compared with placebo plus diet was associated with significant improvement in glycemic control, as reflected in decreases in HbA1c (P < 0.001) and fasting plasma glucose (P < 0.001) and in dosage reductions of oral sulfonylurea medication (P < 0.01). Orlistat therapy also resulted in significantly greater improvements than placebo in several lipid parameters, namely, greater reductions in total cholesterol, (P < 0.001), LDL cholesterol (P < 0.001), triglycerides (P < 0.05), apolipoprotein B (P < 0.001), and the LDL-to-HDL cholesterol ratio (P < 0.001). Mild to moderate and transient gastrointestinal events were reported with orlistat therapy, although their association with study withdrawal was low. Fat-soluble vitamin levels generally remained within the reference range, and vitamin supplementation was required in only a few patients.
                Orlistat is an effective treatment modality in obese patients with type 2 diabetes with respect to clinically meaningful weight loss and maintenance of weight loss, improved glycemic control, and improved lipid profile. To investigate the weight-reducing effect of cimetidine in overweight patients with Type 2 diabetes.
                A 12-week clinical intervention study of 400 mg cimetidine prescribed three times daily in a randomised, double-blind, placebo-controlled design.
                Forty-three overweight patients with Type 2 diabetes (age 18-65 y, body mass index (BMI) 27.2-48.2 kg/m2).
                Body weight, BMI, body fat, waist and hip circumference, waist/hip ratio, blood pressure, fasting blood glucose, HbA1c, plasma concentrations of insulin, insulin/glucose ratio and lipids at the start and after 12 weeks, and daily recordings of appetite.
                Subjects given cimetidine (n = 19) and placebo (n = 24) lost 5.0 +/- 2.2 kg (mean +/- s.d.) and 1.3 +/- 1.1 kg, respectively. Significant reductions were observed in appetite, body fat (29.9 +/- 6.6% to 25.3 +/- 7.4%), waist circumference (111.5 +/- 10.3 cm to 107.4 +/- 10.6 cm), waist/hip ratio (0.96 +/- 0.08 to 0.94 +/- 0.08), and systolic and diastolic blood pressure (reductions of 6.9 +/- 11.4 mm Hg and 6.0 +/- 6.6 mm Hg, respectively) in cimetidine group only. Significant decreases in fasting concentrations of blood glucose, HbA1c, plasma insulin, insulin/glucose ratio, plasma triglycerides and a significant increase in plasma high-density lipoprotein cholesterol were observed in the cimetidine group only.
                Cimetidine reduces appetite and body weight, and improves metabolic control in overweight subjects with Type 2 diabetes. We evaluated the effects of 12-month treatment with sibutramine 15 mg daily compared with placebo on health-related quality of life (HRQL) in obese type II diabetes patients. We examined the associations between the changes in HRQL and in weight, glycaemic control, and haemodynamic variables. We also explored the predictive value of HRQL and its changes early during treatment.
                A randomised clinical trial. The subjects were enrolled in a 2-week single-blind run-in period with a modestly hypocaloric diet (700 kcal daily deficit) and then randomised to receive either sibutramine 15 mg (n=114, 60% female) or placebo (n=122, 58% female) once daily with the hypocaloric diet for 12 months.
                Obese (mean BMI 36 kg/m(2) and age 54 y) type II diabetes patients untreated with antidiabetic medications.
                The main outcome measures included body weight and HRQL (the RAND 36-Item Health Survey 1.0).
                The mean weight loss was greater in the sibutramine group (-7.1 kg) than in the placebo group (-2.6 kg, P<0.001). The baseline HRQL was relatively high. There were no significant differences between the treatment groups in glycaemic control or in any of the RAND-36 scales during the study. The scores on physical functioning (PF) and health change (HC) since last year improved in both groups and this improvement was related to weight loss. When HRQL changes were examined in categories of weight loss, the scores on PF and HC increased with >/=5% weight loss, but the scores on vitality (V) and general health (GH) increased only after >/=15% weight loss. Decrease in HbA1c was associated with increases in the scores of PF, GH, V, mental health, and HC. In the sibutramine group, the increase in diastolic blood pressure was associated with the decrease in the scores of PF, physical role functioning, emotional role functioning (ERF), social functioning (SF), and bodily pain. High baseline scores on ERF and SF, and low scores on V predicted weight loss at 12 months. Also, increasing scores on PF and V during the first 3 months predicted weight loss at 12 months. The sum of four dichotomised HRQL variables (baseline ERF >/=75=1 and <75=0; baseline SF>/=80=1 and <80=0; 3-month change in PF>0=1 and </=0=0; 3-month change in V>0=1 and </=0=0) predicted weight loss: In the group with sum 0, the mean(s.d.) weight change at 12 months was 0.0(2.6)% and with sum 4 it was -9.0(8.1)% of baseline weight.
                Despite the superior weight loss, sibutramine 15 mg daily did not produce HRQL benefits over placebo when measured with the generic RAND-36 in obese type II diabetes patients. PF and HC since last year improved with >/=5% weight loss, but >/=15% weight loss was needed to achieve a cluster of HRQL improvements. The decrease in HbA1c was associated with many HRQL benefits. Poor baseline HRQL and the improvement observed in the first months of treatment may prove to be useful in predicting success in long-term weight loss. Serotonin-releasing agents prescribed as weight-loss medications have been implicated as a cause of acquired aortic and mitral valve abnormalities. Sibutramine hydrochloride (MERIDIA) is a serotonin and norepinephrine reuptake inhibitor with proven efficacy of weight reduction. The purpose of this study was to determine the incidence of cardiac valve disease in sibutraminetreated patients.
                Obese patients with type 2 diabetes mellitus enrolled in an ongoing double-blind, placebo-controlled, parallel-arm, 12-month study of sibutramine (followed by a 12-month open label extension) underwent transthoracic echocardiographic imaging and color Doppler interrogation for assessment of cardiac valve anatomy and function.
                A total of 210 patients were evaluated. Of these, 133 were receiving sibutramine (72 in the double-blind period), and 77 were receiving placebo. The mean+/-Standard Deviation age was 54+/-9 years, and the mean duration of treatment was 229+/-117 days (approximately 7.6 months). The prevalence of left-sided cardiac valve dysfunction was low and similar for the two treatment groups (sibutramine 3/133, or 2.3%; placebo 2/77, or 2.6%). All five cases were cases of aortic insufficiency; four were mild, one was severe (in a placebo patient). All three sibutramine cases were patients over age 50; two had a history of systemic hypertension.
                The prevalence of left-sided cardiac valve dysfunction was not higher than background in obese patients treated with sibutramine for an average of 7.6 months. A double-blind placebo-controlled trial was conducted, involving 97 obese diabetic and glucose intolerant patients receiving either 60 mg fluoxetine daily (47 patients) or a placebo (50 patients); a similar calorie-restricted diet was prescribed to all patients. Weight loss was significantly higher in the fluoxetine-treated patients, whose diabetic status improved. Drop-out rate was not significantly different for both groups of patients. The use of an anorectic drug (mazindol) did not significantly interfere with the therapy needed to maintain control in obese diabetics. In two of four insulin-requiring patients, a reduction of the insulin requirement occurred when weight was lost. No change was needed in oral hypoglycaemic therapy in the six weeks of the trial. nan In a double-blind study 40 overweight maturity-onset diabetics on a weight-reducing diet were randomly assigned to treatment with either the appetite-suppressant diethylpropion hydrochloride (Tenuate), or placebo. After treatment for 8 weeks the mean weight loss achieved by each group was 4.9 and 3.3%, respectively. This approximately equal weight loss was too slight to exert any significant effect on glucose tolerance. Thus, an additional effect of this anorexiant in comparison with diet restriction alone, as described in obese non-diabetic subjects, is not evident in the case of obese diabetic patients. The purpose of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on body weight, glycemic control, and cardiovascular risk factors in metformin-treated type 2 diabetic patients.
                A 1-year multicenter, randomized, double-blind, placebo-controlled trial of 120 mg orlistat t.i.d. (n = 249) or placebo (n = 254) combined with a reduced-calorie diet was conducted in overweight and obese patients with suboptimal control of type 2 diabetes.
                After 1 year of treatment, mean (+/-SE) weight loss was greater in the orlistat than in the placebo group (-4.6 +/- 0.3% vs. -1.7 +/- 0.3% of baseline wt, P < 0.001). Orlistat treatment caused a greater improvement in glycemic control than placebo, as evidenced by a greater reduction in serum HbA(1c), adjusted for changes in metformin and sulfonylurea therapy (-0.90 +/- 0.08 vs. -0.61 +/- 0.08, P = 0.014); a greater proportion of patients achieving decreases in HbA(1c) of > or = 0.5 and > or = 1.0% (both P < 0.01); and a greater reduction in fasting serum glucose (-2.0 +/- 0.2 vs. -0.7 +/- 0.2 mmol/l, P = 0.001). Compared with the placebo group, patients treated with orlistat also had greater decreases in total cholesterol, LDL cholesterol, and systolic blood pressure (all P < 0.05). Although more subjects treated with orlistat experienced gastrointestinal side effects than placebo (83 vs. 62%, P < 0.05), more subjects in the placebo group withdrew prematurely from the study than in the orlistat group (44 vs. 35%, P < 0.05).
                Orlistat is a useful adjunctive treatment for producing weight loss and improving glycemic control, serum lipid levels, and blood pressure in obese patients with type 2 diabetes who are being treated with metformin. To assess the effect of orlistat on body weight and cardiovascular risk amongst obese patients at high coronary risk.
                After screening, patients entered a two-week single-blind placebo lead-in period, during which they followed a mildly hypocaloric diet, before being randomized to double-blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with dietary intervention for 1 years.
                The study was conducted at 33 primary care centres in Sweden.
                A total of 382 obese adults (body mass index 28-38 kg m-2) with type 2 diabetes, hypercholesterolaemia and/or hypertension were recruited, of whom 376 were randomized to orlistat (n = 190) or placebo (n = 186).
                Change in body weight, waist and hip circumferences, blood pressure, serum lipid profile, fasting glucose and HbA1c.
                After 1 years, mean weight loss was significantly greater with orlistat compared with placebo (5.9% vs. 4.6%; P < 0.05). Moreover, significantly more orlistat-treated patients than placebo recipients maintained weight loss of > or = 5% (54.2% vs. 40.9%; P < 0.001). Orlistat was also associated with significantly greater improvements than placebo in total serum cholesterol (- 3.3% vs. -0.5%; P < 0.05), LDL-cholesterol (- 7.0% vs. -1.1%; P < 0.05), fasting glucose (5.1% vs. -0.1%; P < 0.01) and HbA1c (- 2.7% vs. -0.5%; P < 0.05). Similar results were reported for the subgroup of patients with type 2 diabetes. Orlistat was well tolerated.
                Treatment with orlistat in conjunction with diet promotes significantly greater weight loss and cardiovascular risk factor reduction than diet alone amongst obese patients at high risk of future coronary events. To assess the long-term effects of orlistat on body weight, glycaemic control and cardiovascular risk factors in overweight patients with type 2 diabetes.
                This was a multicentre, randomized, placebo-controlled study with a 4-week placebo plus diet lead-in period and a 48-week, double-blind treatment period. Overweight or obese adults [body mass index (BMI) >or= 28 kg/m2] with HbA1c of 6.5-11% and clinical type 2 diabetes were randomized to orlistat (120 mg t.i.d. n = 189) or placebo (n = 180) in conjunction with a low-calorie diet. Patients had either received sulphonylurea therapy for at least 2 months before the study or were not receiving any antidiabetic medication (the majority of which were drug-naïve).
                After 1 year, patients in the orlistat group lost significantly more weight than patients in the placebo group (-5.4% vs. -3.6%; p = 0.006). Moreover, significantly more patients achieved weight loss of >or= 5% with orlistat compared with placebo (51.3% vs. 31.6%; p = 0.0001). Patients treated with orlistat also had significantly greater improvements than placebo-treated patients in HbA1c (-0.9% vs. -0.4%; p < 0.001), fasting glucose (-1.6 vs.-0.7 mmol/l; p = 0.004) and post-prandial glucose (-1.8 vs. -0.5 mmol/l; p = 0.003). In addition, orlistat-treated patients had a significantly greater reduction in LDL cholesterol compared with placebo. Overall, orlistat had a similar safety profile to placebo, with the exception of a higher incidence of generally mild and transient gastrointestinal events known to be associated with the mode of action of orlistat.
                Treatment with orlistat plus diet resulted in significant weight loss, improved glycaemic control and cardiovascular risk factor profile in overweight patients with type 2 diabetes. In order to establish the safety and efficacy of fluoxetine in subjects over 60 years of age with Type 2 diabetes, a randomized, double-blind, parallel study of 30 obese subjects was undertaken, comparing the use of fluoxetine 60 mg daily with placebo. Subjects were diet controlled with an HbA1 < 14% (reference range 6-9%) and BMI > 29 kg m2. Those taking fluoxetine had a median weight loss of 2.6 kg at 3 months (p < 0.001) and 3.9 kg at 6 months (p < 0.02), compared with weight loss in the placebo group of 0.1 kg and 0.0 kg at 3 and 6 months, respectively. Improved glycaemic control was also demonstrated in the fluoxetine group compared with placebo, initial HbA1 levels of 8.0% vs 8.7% (NS) falling at 4 months by 0.9% (p < 0.02) and at six months by 0.9% (p < 0.02). No sustained improvement in fasting blood glucose levels was demonstrated. Reporting of adverse events was similar in both groups. Fluoxetine in the short term aids weight loss and improves glycaemic control without a significant increase in adverse events in elderly Type 2 diabetic subjects. To investigate whether the satiety-inducing agent sibutramine affected body weight and associated anthropometry in overweight and obese (body mass index (BMI) > 27) Type 2 diabetic patients on sulphonylurea therapy.
                A randomized, placebo-controlled trial was undertaken in 134 patients with stable metabolic control on chronic sulphonylurea therapy. Patients were placed on moderate caloric restriction and received treatment with either sibutramine (15 mg/day) or placebo for 6 months.
                Fifty-three of 69 sibutramine-treated and 57/65 placebo-treated patients completed the study. Both groups showed progressive weight loss. At the end of the trial weight loss was two times greater in the sibutramine group (mean +/- SEM; -4.5 +/- 0.5 kg) than placebo (-1.7 plus minus 0.5 kg, P < 0.001 vs. sibutramine). There was a trend for more patients to lose > 5% of initial body weight in the sibutramine group than placebo. BMI (P < 0.001) and waist circumference (P < 0.001) were also decreased to a greater extent by sibutramine. Mean reductions in HbA(1c) were commensurate with weight loss in both the sibutramine and placebo (- 0.78 +/- 0.17% and -0.73 +/- 0.23%; P = 0.84). Sibutramine was well tolerated with only two patients withdrawn due to potentially drug-related serious adverse events (palpitations).
                Sibutramine, in conjunction with moderate caloric restriction, enhances weight loss and reduces waist circumference in overweight and obese Type 2 diabetic patients receiving sulphonylurea therapy. This is associated with additional improvements in glycaemic control in a limited number of patients losing > or = 10% of their baseline body weight. Fluoxetine, an inhibitor of serotonin re-uptake, has been shown to cause weight loss in humans and animals. In order to determine the effects in diabetic subjects, 48 male and female, obese, type 2 non-insulin dependent diabetics being treated with insulin were randomized to receive fluoxetine 60 mg or placebo once daily in double blind fashion for 24 weeks. In all subjects, this treatment was preceded by four weeks and followed by six weeks of single blind placebo washout treatment. Subjects performed daily home glucose monitoring and were given instruction in a 1200 kcal American Diabetes Association diet. Fluoxetine treated subjects who completed the trial (n = 16) lost more weight than placebo treated subjects (n = 20) (9.3 +/- 2.4 vs. 1.9 +/- 2.9 kg +/- s.e.m, P less than 0.05). Subjects in the fluoxetine group also showed a greater percentage decrease in insulin dose than those in the placebo group (46.9 +/- 7.6% vs. 19.3 +/- 7.6%, P less than 0.01). During active treatment, the change in serum glucose levels did not differ between the two groups, while glycohemoglobin fell more in fluoxetine treated subjects than in placebo treated subjects at two of four follow-up visits. These results suggest that fluoxetine may be of benefit in the treatment of obese patients with type 2 non-insulin dependent diabetes mellitus. To determine the efficacy and tolerability of sibutramine hydrochloride in obese patients whose type 2 diabetes was poorly controlled on diet alone or with an oral antidiabetic agent.
                This study was a 24-week, double-blind, multicentre trial following a 5-week placebo run-in period. One hundred and seventy-five obese (body mass index (b.m.i.) > or =27 kg/m2) patients with poorly controlled type 2 diabetes mellitus were randomized either to sibutramine (n = 89; mean age 53.5 years; mean weight 99.3 kg) or placebo (n = 86; mean age 55 years; mean weight 98.2 kg) at 16 participating centres. To achieve moderate calorie restriction (deficit > or = 250-500 kcal/day), individual dietary counselling was accompanied by either placebo or sibutramine (initial dosage of 5 mg/day titrated up by 5 mg biweekly through week 6, and maintained at 20 mg through week 24). The main outcome measures included changes in weight, b.m.i., waist and hip circumference, glycaemic control, lipid profile, and quality of life, and evaluation of reported adverse events.
                Sixty-seven per cent of sibutramine patients and 71% of placebo patients completed the study. At week 24 when comparing those who completed the course, sibutramine compared with placebo patients showed significantly greater (p < 0.001) absolute (-4.3 vs. -0.4 kg) and percentage (-4.5% vs. -0.5%) weight loss. Weight loss > or =5% or 10% was achieved by 33% and 8% of sibutramine patients, respectively, but no placebo patients (p < 0.03 or better). Improvement in glycaemic control was correlated with weight loss (p < 0.001). In 5% and 10% weight-loss responders, mean treatment differences were -0.53% and -1.65% (p < or = 0.05), respectively, for HbA1c, and -1.4 mmol/l (p < or =0.05) and -3.8 (p < or =0.05) mmol/l for fasting plasma glucose. Sibutramine patients also showed improvements in fasting insulin, triglycerides, HDL cholesterol, and quality-of-life assessments. Overall, sibutramine was well tolerated compared with the placebo. Sibutramine treatment was associated with small mean increases in blood pressure (BP) and pulse, although an increase in BP was not seen in sibutramine-treated patients who lost > or = 5% of their weight.
                Sibutramine produced statistically and clinically significant weight loss when used in combination with recommendations for moderate caloric restriction. This weight loss was associated with improvements in metabolic control and quality of life, and sibutramine was generally well tolerated in obese patients with type 2 diabetes. In a 12-month randomly allocated double-blind trial in 19 obese Type 2 diabetic patients, fluoxetine 60 mg daily compared to placebo produced a significant fall in median body weight after 3 months (3.8 kg), 6 months (6.5 kg), 9 months (7.1 kg) and at 1 year (5.8 kg). Median fasting blood glucose and HbA1c levels fell significantly after 3 months (1.9 mmol l-1) and 1.7%, respectively) and 6 months (1.8 mmol l-1 and 1.7%) but neither showed a significant difference to placebo after 9 or 12 months therapy with fluoxetine. There were no significant changes in serum cholesterol levels in the year but patients on fluoxetine showed a significant fall in serum triglyceride level (0.5 mmol l-1) after 3 months therapy but not thereafter. Compared to placebo there was a significant fall in median energy intake on fluoxetine after 3 months (257 kcal day-1) and 6 months (199 kcal day-1) but this difference was not significant at 9 or 12 months. There was also a significant fall in carbohydrate intake after 3 months (30 g day-1) and 6 months (23 g day-1) on fluoxetine as well as a significant fall in carbohydrate intake expressed as a percentage of the total daily energy intake; 5.9% at 3 months, 6.1% at 6 months, and 4.0% at 9 months. There were no significant effects on protein or fat intake except a significant increase in the intake of fat expressed as a percentage of daily energy intake, 5.9% after 6 months. Two of the nine patients on fluoxetine dropped out of the study due to gastrointestinal side-effects. Fluoxetine might prove to be a useful adjunct therapy in obese Type 2 diabetic patients where short-term weight loss and fall in carbohydrate intake and an improvement in glycaemia are indicated. The purpose of this study was to evaluate the effects of a combination weight loss program using intermittent low-calorie diets, energy-controlled meal replacement products, and sibutramine on weight loss, diabetes control, and cardiovascular risk factors in overweight or obese subjects with type 2 diabetes.
                Overweight or obese individuals with type 2 diabetes treated with diet or oral medication were randomly assigned to either a standard therapy or combination therapy group. Both groups received a standardized program to facilitate weight loss. The combination therapy group also received 10-15 mg sibutramine daily, low-calorie diets using meal replacement products for 1 week every 2 months, and between low-calorie diet weeks, once daily use of meal replacement product and snack bars to replace one usual meal and snack. Primary outcome measures were changes in body weight, glycemic control, plasma lipids, blood pressure, pulse, and body composition at 1 year.
                At 1 year, combination therapy, compared with standard therapy, resulted in significantly more weight loss (-7.3 +/- 1.3 kg vs. -0.8 +/- 0.9 kg, P < 0.001) and reduction in HbA(1c) (-0.6 +/- 0.3 vs. 0.0 +/- 0.2%, P = 0.05). Combination therapy resulted in reduced requirement for diabetes medications and decreased fat mass and lean body mass. A 5-kg decrease in weight at 1 year was associated with a decrease of 0.4% in HbA(1c) (P = 0.006). Changes in fasting glucose, lipids, pulse, and blood pressure did not differ between groups.
                This combination weight loss program resulted in greater weight loss and improved diabetes control compared with a standard weight loss program in overweight or obese subjects with type 2 diabetes. nan nan To assess the effect of orlistat plus diet compared with diet alone in promoting weight loss and blood pressure reduction in hypertensive, overweight/obese patients.
                A pragmatic randomized, controlled trial.
                Hypertension clinic of a university hospital.
                Hypertensive patients aged 18-75 years with a body mass index greater than 25 kg/m(2).
                Orlistat 360 mg/day combined with a hypocaloric diet (treatment group), or a calorie-restricted diet alone (control group).
                Primary outcomes were reductions in weight and blood pressure. Secondary outcomes were decreases in lipid and glucose concentrations. A subgroup analysis of the main outcomes among diabetic and non-diabetic patients was also performed.
                A total of 204 patients were included in the intention-to-treat analysis. After 12 weeks the orlistat group lost, on average, 3.7 kg and the control group lost 2.0 kg in weight (P < 0.001). Systolic (SBP) and diastolic (DBP) blood pressures decreased by 15.3 and 11.4 mmHg, respectively, in the group given orlistat plus a hypocaloric diet and by 11.6 and 5.2 mmHg, respectively, in the control group given the calorie-restricted diet alone (P = 0.25 and P = 0.0004, respectively). Fasting glucose (0.82 and 0.17 mmol/l, P = 0.01) and total cholesterol (0.85 and 0.56 mmol/l, P = 0.05) were reduced to a greater extent with orlistat than with diet alone. The mean reduction in triglycerides with orlistat plus the hypocaloric diet was 0.75 mmol/l and that in the control group was 0.30 mmol/l (P = 0.28); the increases in high-density lipoprotein cholesterol were 0.05 and 0.00 mmol/l, respectively, in the two groups (P = 0.17). Treatment improved blood pressure and glucose control in the individuals with diabetes, but not in those without diabetes.
                In both groups there was a reduction in weight, blood pressure and metabolic parameters. The orlistat group performed better in reducing weight, DBP, glucose and cholesterol. Results show that even a small reduction in weight helps to control blood pressure and glucose. The cost-benefit of the use of orlistat should be evaluated for hypertensive obese patients. nan An open, non-comparative study was carried out to assess the efficacy and toleration profile of sibutramine, a new antiobesity drug, in promoting weight loss in obese type 2 diabetes mellitus subject who failed to reduce weight after strict dietary control. Twenty seven patients completed the study. Sibutramine was started as a single morning dose of 10 mg and was subsequently increased to 15 mg daily if weight loss was not satisfactory. The total duration of the study was twelve weeks with followup at every four weeks. Effect of drug was monitored in terms of weight reduction, changes in body mass index, waist circumference, hip circumference, waist/hip ratio and other metabolic parameters. A fixed dietary prescription and concomitant therapy with drugs, if required and not likely to interfere with the trial therapy, was permitted but was not changed during the study period.
                At the end of 12 week, mean weight reduction in study subjects was 4.16 kg (p < 0.001), the corresponding BMI decreased by 1.6 (p < 0.0001) and hip circumference by 3.68 (p < 0.001). However, there was no significant change in fasting blood glucose and Hb(A1c) values.
                The study indicates sibutramine to be an effective and well tolerated agent leading to significant reduction in parameter of obesity in obese type 2 diabetic subjects. OBJECTIVE; Weight loss improves glycemic control, lipid profiles, and blood pressure in patients with type 2 diabetes. However, successful long-term weight loss is difficult for these patients, particularly those treated with insulin. The aim of this study was to assess the effect of orlistat, a gastrointestinal lipase inhibitor, on weight loss, glycemic control, and cardiovascular risk factors in overweight or obese insulin-treated type 2 diabetic patients.
                This study was a 1-year multicenter, randomized, double-blind, placebo-controlled trial of orlistat (120 mg three times a day) or placebo combined with a reduced-calorie diet in overweight or obese adults (BMI 28-40 kg/m(2)) with type 2 diabetes treated with insulin alone or combined with oral agents, but with suboptimal metabolic control (HbA(1c) 7.5-12.0%). Outcome measurements included changes in body weight, glycemic control, blood pressure, and serum lipids. RESULTS; After 1 year, the orlistat group lost significantly more weight (-3.89 +/- 0.3% of baseline body weight, means +/- SE) than the placebo group (-1.27 +/- 0.3%, P < 0.001). Orlistat treatment, compared with placebo, produced greater decreases in HbA(1c) (-0.62 +/- 0.08 vs. -0.27 +/- 0.08%, P = 0.002), fasting serum glucose (-1.63 +/- 0.3 vs. -1.08 +/- 0.3 mmol/l, P = 0.02), and the required doses of insulin and other diabetic medications. Orlistat also produced greater improvements than placebo in serum total cholesterol (P = 0.0002) and LDL cholesterol concentrations (P = 0.001) and LDL/HDL ratio (P = 0.01). CONCLUSIONS; Orlistat therapy produces clinically significant weight loss, with improvements in glycemic control and cardiovascular disease risk factors, in overweight or obese patients with type 2 diabetes who have suboptimal metabolic control with insulin therapy. Mazindol, a drug with tricyclic structure unrelated to amphetamine and other anorectic drugs, has been used as an anorectic agent in a double blind clinical trial at a dose of 2 mg/day for 12 week (mazindol v. s. placebo), associated with a 1000 calorie diet on 46 obese diabetic patients. Thirty seven patients completed the trial with no significant difference between the two groups in the drop-out population; mazindol was well tolerated. In the mazindol-treated group the mean weight loss was 13.5 kg (22.3%) which was significantly greater (p less than 0.001) than in the placebo treated group where the mean weight loss was 4.2 kg (9.8%). Comparing the two groups after the 12 week trial, decrease in fasting blood glucose, serum insulin and triglycerides was not significant. In the mazindol-treated group a significant decrease of serum cholesterol, triglycerides and of the mean area under the curve of insulinemia during the OGTT has been observed. In the placebo treated group only serum triglycerides decreased significantly. The variations of plasma insulin and serum cholesterol were found to be correlated to the magnitude of weight loss. In conclusion mazindol is an effective drug for weight loss on the whole well tolerated but without specific properties on metabolism. To assess the efficacy and tolerability of sibutramine 15 mg once daily as a weight reduction agent in overweight and obese patients (body mass index (b.m.i.) > 26 kg/m2) with type 2 diabetes when given with a customised, reduced-calorie diet, and to evaluate the influence of weight loss on diabetic control.
                Randomised, placebo-controlled, double-blind, parallel-group, 12-week study conducted at two hospital-based obesity/diabetes clinics. Patients were men and women aged 30-65 years, with b.m.i. > 26 kg/m2 and < or = 35 kg/m2 and treated or untreated type 2 diabetes diagnosed > or = 6 months previously. Each patient was given sibutramine 15 mg or placebo once daily and advised to follow a customised diet of 500 kcal/day less than the individual's energy needs. The principal measure of efficacy was change in body weight (b.w.). Additional efficacy measurements were changes in b.m.i., body composition as measured by dual-energy X-ray absorptiometry, and change in waist and hip measurements. Changes in diabetic control were assessed by blood glucose levels fasting and after a standard test meal, fasting insulin level, and glycosylated haemoglobin level. Adverse events (AEs) were monitored at each visit, and routine laboratory safety tests were done at 4-week intervals.
                Ninety-one patients were randomised into the study, 44 to placebo and 47 to sibutramine 15 mg once daily. Eighty-three patients (91%) completed the study, 40 (91%) on placebo and 43 (91%) on sibutramine. Mean weight reduction from baseline was statistically significantly greater with sibutramine than with placebo at every measurement and at the end of the study (2.4 vs. 0.1 kg at week 12; p < 0.001; intent-to-treat). The proportion of patients who lost > 5% of their baseline b.w. was 19% in the sibutramine group and 0% in the placebo group (p < 0.001; 95% confidence interval: 9, 30). Patients receiving sibutramine lost significantly more fat mass compared with those receiving placebo, as a percentage (1.0% vs. 0.1%; p < 0.05) and in absolute terms (1.8 vs. 0.2 kg, p < 0.001). Loss of lean mass was not significantly different between the groups. Mean peak blood glucose concentration after a standard test meal decreased by 1.1 mmol/l in the sibutramine treatment group but increased by 0.5 mmol/l in the placebo group (p = 0.04; difference in means, 1.6, 95% confidence interval: -3.3, -0.1). Mean fasting blood glucose decreased by 0.3 mmol/l with sibutramine and increased by 1.4 mmol/l with placebo. Mean glycosylated haemoglobin levels decreased by 0.3% units with sibutramine treatment, and were unchanged with placebo. However, more sibutramine-treated patients (33%) than placebo-treated patients (5%) achieved decreases in glycosylated haemoglobin of 1% unit or more (p < 0.05). Sibutramine 15 mg was safe and well tolerated, and AEs were mostly mild or moderate in severity. No significant differences were found between treatment groups in blood pressure. No clinically significant conduction or rhythm abnormalities were observed on ECG.
                Sibutramine 15 mg once daily with a customised, reduced-calorie diet significantly reduced weight compared with placebo in overweight and obese patients (b.m.i. > 26 kg/m2) with type 2 diabetes. Sibutramine was well tolerated, and significant improvement in diabetic control was seen in conjunction with weight reduction on sibutramine treatment. Moderate weight loss is recommended for overweight and obese patients with type 2 diabetes, and conjunctive use of weight loss medication has been advocated. The current study examined weight loss-dependent and -independent effects of the intestinal lipase inhibitor orlistat at 6 months of treatment, using behavioral intervention (Int) combined with randomized, double-blinded, placebo (P)-controlled treatment with orlistat (O).
                Metabolic control, insulin sensitivity (IS), regional fat distribution, and fat content in liver and muscle were measured in 39 volunteers with type 2 diabetes in whom all antidiabetic medication was withdrawn 1 month preceding randomization. Weight loss was equivalent in the Int+O and Int+P groups, respectively (-10.3 +/- 1.3 vs. -8.9 +/- 1.1%), and there were identical decreases in visceral adipose tissue (VAT), fat mass (FM), thigh adiposity, and hepatic steatosis.
                Weight loss resulted in substantial improvement (P < 0.001) in HbA(1c) (-1.6 +/- 0.3 vs. -1.0 +/- 0.4%; NS between groups). IS improved significantly more with orlistat (Delta2.2 +/- 0.4 vs. Delta1.2 +/- 0.4 mg. min(-1). kg(-1) fat-free mass [FFM]; P < 0.05), and plasma free fatty acid (FFA) levels were strongly correlated with IS (r = 0.56; P < 0.001). Orlistat caused greater reductions in fasting plasma FFA (Delta-154 +/- 22 vs. Delta-51 +/- 33 micro mol/l; P < 0.05), insulin-suppressed FFA (Delta-119 +/- 23 vs. Delta-87 +/- 34 micro mol/l; P < 0.05), and fasting plasma glucose (FPG; -62 +/- 9 vs. -32 +/- 8 mg/dl; P = 0.02). Changes in HbA(1c) were correlated with DeltaIS (r = -0.41; P < 0.01) but not with weight loss per se.
                At equivalent weight loss, conjunctive use of orlistat resulted in greater improvement in FFA levels and IS. nan In this study, we evaluated the efficacy of sibutramine in combination with hypoglycemic drugs in obese type 2 diabetic women whose glucose levels were poorly regulated.
                Female patients with type 2 diabetes, poorly controlled glucose levels, and HbA(1c) >8% were randomly assigned to one of two groups. In addition to their prescribed hypoglycemic agents (maximum doses of sulfonylureas and metformin), one group (n = 30) received a placebo twice daily for 6 months and the other (n = 30) received sibutramine 10 mg b.i.d. for the same period.
                One patient in the sibutramine group was excluded during the study period because of hypertension; thus, a total of 29 data sets were analyzed for this group. In the placebo group, five patients had to be excluded because of low treatment efficacy, leaving a total of 25 who completed the study. Comparing the changes that occurred over 6 months in the sibutramine and placebo groups, the former showed significantly greater reductions in fasting blood glucose (P < 0.0001), second-hour postprandial blood glucose (P < 0.0001), insulin resistance (P < 0.0001), waist circumference (P < 0.0001), BMI (P < 0.0001), HbA(1c) (P < 0.0001), diastolic blood pressure, pulse rate, uric acid levels, and all elements of the lipid profile except HDL cholesterol and apolipoprotein A1.
                The addition of sibutramine to oral hypoglycemic therapy resulted in significant weight loss and improvement in metabolic parameters in this patient group. Sibutramine is an effective adjunct to oral hypoglycemic therapy in obese women with type 2 diabetes. nan
Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes.