rosiglitazone-metformin-combination and Weight-Gain

To assess 12-month body weight (BW) and body composition changes in normoglycemic women with midlife weight gain, after dietary and pharmacologic interventions targeting hyperinsulinemia.. EMPOWIR (Enhance the Metabolic Profile of Women With Insulin Resistance; NCT00618072) was a double-blind, placebo-controlled, 12-month trial of women with >20-pound weight gain, normal glucose tolerance test, and increased area-under-the-curve insulin. Subjects (mean ± SD, 46.7 ± 6.5 years of age; body mass index, 30.8 ± 2.8 kg/m(2); 50% white) attended 4 nutrition workshops to introduce a novel carbohydrate-modified diet (CMD) and were then randomized to one of three arms for 6 months (phase 1): CMD alone (D), or in combination with metformin (M), or metformin + rosiglitazone (MR), with rerandomization of the D group to one of the active treatment arms (phase 2, months 7 through 12). Repeated measure analysis of variance was used to assess BW at baseline, 6 months, and 12 months in 32 subjects with 12-month data; paired t tests compared baseline and 12-month dual-energy X-ray absorptiometry-derived body composition.. Mean (±SD) BW decreased significantly at 12 months in the M arm: 85.1 ± 8.5 kg to 79.8 ± 9.0 kg (P = .0003), with 54% of variance in weight over time explained by M treatment. Mean (±SD) percent android fat decreased significantly in the M and D arms: 53.5 ± 4.8% to 49.3 ± 7.6% (P = .010) and 52.9 ± 6.2% to 48.1 ± 8.7% (P = .021).. In combination with a novel carbohydrate modified diet, metformin enhanced 12-month weight loss and improved body composition in ethnically diverse normoglycemic, hyperinsulinemic women with midlife weight gain. These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies.

Topics: Adipose Tissue; Adult; Aging; Body Fat Distribution; Climacteric; Double-Blind Method; Drug Combinations; Female; Humans; Insulin Resistance; Metformin; Middle Aged; Obesity; Overweight; Placebos; Thiazoles; Weight Gain; Weight Loss

Commercialization of rosiglitazone, an oral blood glucose-lowering drug of the thiazolidinedione class, was recently suspended in Europe and significantly restricted in the United States due to a possibly increased risk of ischemic heart disease; the drug is still being marketed in Mexico. This study was aimed to analyze the post-marketing occurrence of adverse drug reactions (ADRs) with rosiglitazone when used in combination therapy in Mexican Type 2 Diabetes patients.. A prospective observational study was conducted at a primary health-care clinic in Mexico City. Eligible subjects were adult patients with Type 2 diabetes inadequately controlled with maximal doses of oral monotherapy, in which one of two combined therapeutic schemes was prescribed: rosiglitazone/glibenclamide (R/G), or rosiglitazone/metformin (R/M). Patients' blood pressure, weight, treatment adherence and occurrence of ADRs were monitored during a 6-month follow-up period.. 174 patients received treatment with R/M or R/G (112 and 62 patients, respectively). At least one ADR was observed in about 75%, of patients. Prior to the end of the follow-up period, moderate ADRs leading to discontinuation of the treatment occurred in 29.5% and 14.5% of patients treated with R/M and R/G, respectively. The ADRs most frequently observed were peripheral edema and moderate weight gain.. The use of rosiglitazone in combination with other oral anti-diabetic drugs was associated with a high frequency of ADRs in Mexican patients with Type 2 diabetes. Post-marketing studies are relevant to identify drug-associated risks to patients in clinical practice.

Topics: Administration, Oral; Adult; Aged; Diabetes Mellitus, Type 2; Drug Combinations; Edema; Female; Follow-Up Studies; Glyburide; Humans; Hypoglycemic Agents; Male; Medication Adherence; Metformin; Mexico; Middle Aged; Pharmacovigilance; Prospective Studies; Rosiglitazone; Thiazoles; Thiazolidinediones; Weight Gain