Endocannabinoid Blockade for Improving Glycemic Control and Lipids in Patients with Type 2 Diabetes Mellitus
Section snippets
CVD Risk, Type 2 Diabetes, and the Metabolic Syndrome
The extent to which diabetes increases CVD risk underscores the importance of optimal diabetes management. There has been debate over whether patients with diabetes should be managed as aggressively for CVD risk factors as patients who have had a previous myocardial infarction (MI). A 7-year MI incidence study was done to address this issue (Figure 1).10 A Finnish population of patients with (n = 1,059) and without (n = 1,373) diabetes, both with and without prior MI, were compared. As
The Therapeutic Gap in Type 2 Diabetes Treatment
As stated earlier, aggressive, multimodal CVD risk management has become the standard of care because, to date, it has demonstrated the highest degree of success. As demonstrated in the Steno-2 study, through aggressive, multimodal therapy it is possible to reduce cardio- and microvascular event rates by about 50% (Figure 2).8 In the Steno-2 study these therapies comprised a stepwise implementation of behavior modification and pharmacologic therapy (not including aspirin for secondary CVD risk
Rimonabant in the Management of Multiple Cardiometabolic Risk Factors
Rimonabant is a selective cannabinoid-1 (CB1) blocker that has demonstrated efficacy in the treatment of overweight and obesity, dyslipidemia, and CVD risk factors (Figure 3).23, 24 The newly discovered endocannabinoid (EC) and CB1 receptor system modulates food intake, energy balance, and body composition through both central and peripheral effects that improve glucose and lipid metabolism.16, 25, 26, 27, 28 CB1 receptors are expressed centrally in several areas of the brain and peripherally
Study Design
RIO-Diabetes was a 12-month, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Rimonabant 5 mg and 20 mg, in combination with a 600-kcal/day [1 kcal = 4.2 kJ] deficit diet and advice regarding physical exercise, was tested against placebo in overweight/obese patients with type 2 diabetes receiving metformin or sulfonylurea monotherapy. It was conducted in 159 center locations in 11 countries and randomized 1,045 patients, 35% of whom were in the
Efficacy Outcomes
Weight loss with rimonabant 5 mg and 20 mg was significantly greater than that with placebo after 1 year (Figure 4 and Table 3). Weight change from baseline in the rimonabant 5-mg and 20-mg groups was loss of 2.3 and 5.3 kg, respectively, compared with 1.4 kg in the placebo (intention-to-treat [ITT], last observation carried forward [LOCF]) group (P = .013 and P <0.001, respectively, vs. placebo). Weight loss in the 20-mg group began to plateau at about 38 weeks, and was maintained through the
Discussion
Results of the RIO-Diabetes study clearly demonstrate that through 1 year, rimonabant 20 mg significantly reduced weight, waist circumference, HbA1c, and a constellation of related pathometabolic CVD risk factors in obese or overweight patients with type 2 diabetes. These patients are resistant to weight loss and susceptible to weight gain, not only because of the pathometabolic nature of type 2 diabetes but also because weight gain is a side effect of several antidiabetes medications used to
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