Fast track — ArticlesEfficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study
Introduction
Type 2 diabetes frequently co-exists with a cluster of other cardiovascular and metabolic risk factors including abdominal obesity, low HDL-cholesterol concentrations, high triglyceride concentrations, and raised blood pressure,1 and is considered to be a cardiovascular disease risk equivalent.2, 3 A recent population-based retrospective cohort study showed that diabetes confers an equivalent cardiovascular risk to ageing 15 years in people aged 40 years or older.4 The treatment of multiple cardiovascular and metabolic risk factors is central to the management of type 2 diabetes.5
Being overweight or obese—in particular, abdominally obese—increases the risk of type 2 diabetes and cardiovascular disease,6, 7 yet those with diabetes often have more difficulty in losing weight8 and experience weight gain associated with most antidiabetic medications.5
The endocannabinoid system, consisting of the cannabinoid type 1 (CB1) receptor and endogenous lipid-derived ligands,9 seems to modulate energy homoeostasis as well as glucose and lipid metabolism,10, 11, 12 both through central orexigenic effects and peripheral metabolic effects in adipose tissue, liver, and skeletal muscle.13, 14, 15 Patients with obesity or hyperglycaemia caused by type 2 diabetes exhibit higher concentrations of endocannabinoids in visceral fat or serum, respectively, than the corresponding controls.16
In non-diabetic overweight or obese patients, 20 mg daily of the selective CB1 receptor blocker rimonabant has been shown to produce substantial weight loss and waist circumference reduction (a key marker of intra-abdominal adiposity), and improvements in multiple cardiovascular and metabolic risk factors.17, 18 These data were further confirmed in overweight or obese patients with untreated dyslipidaemia.19 Part of these metabolic improvements could be attributed to a moderate, but significant, increase in plasma adiponectin levels.19
This multicentre randomised controlled trial was designed to assess the efficacy and safety of rimonabant in combination with a mild hypocaloric diet and advice for increased physical activity in overweight or obese patients with type 2 diabetes who were already on metformin or sulphonylurea monotherapy.
Section snippets
Patients
This randomised, double-blind, placebo-controlled study was done in 159 centres in 11 countries (in Europe, North America, and South America) between October, 2001, and May, 2004. Patients aged 18–70 years with type 2 diabetes who had been treated with metformin or sulphonylurea monotherapy for at least 6 months (stable dose for at least 3 months), but who remained inadequately controlled, were recruited. Inclusion criteria were body-mass index of 27–40 kg/m2, a haemoglobin A1c (HbA1c) level of
Results
513 men and 532 women were randomised to double-blind treatment. 692 patients (66·2%) completed the 1-year follow-up (figure 1). Two randomised patients were not exposed to treatment and 11 randomised patients were excluded from the analysis of weight (two for non-exposure and nine for missing post-baseline weight assessment). Baseline characteristics were much the same in the three groups (table 1), except smoking, which was slightly lower in the 20 mg/day rimonabant group (p=0·02), and
Discussion
The main finding of the RIO-Diabetes trial is that 20 mg/day rimonabant for 1 year significantly reduced weight, waist circumference, and HbA1c levels and improved a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylurea. These results extend previous findings in non-diabetic overweight or obese patients to those with type 2 diabetes.17, 18, 19 Patients with type 2 diabetes are
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