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The type 2 diabetes drug canagliflozin (Invokana) was associated with modest weight loss in an early trial of heavy patients who didn't have hyperglycemia, researchers found.

In a phase IIb trial, obese and overweight patients who didn't have diabetes lost a significantly larger proportion of body weight on any of three doses of the drug compared with placebo (P<0.05), , of Louisville Metabolic and Atherosclerosis Research Center in Kentucky, and colleagues .

This amounted to a "relatively modest" loss of about 2% to 3% of body weight, compared with only about 1% loss with placebo, they wrote.

Canagliflozin is the first sodium glucose co-transporter 2 (SGLT2) inhibitor approved to treat type 2 diabetes in the U.S., and it works by dumping excess blood sugar into the urine.

Researchers have hypothesized that this increased urinary glucose excretion leads to a decline in calories, and hence a reduction in body weight, possibly even in patients who don't have type 2 diabetes.

Several other diabetes drugs have also been investigated for weight loss potential, including liraglutide (Victoza) and . Novo Nordisk, maker of liraglutide, recently announced it would seek FDA approval for liraglutide in weight loss in nondiabetics within the year.

To test canagliflozin's impact on weight loss, Bays and colleagues conducted a 12-week phase IIb trial in 376 patients who were overweight or obese but didn't have type 2 diabetes. Patients were randomized to placebo or to one of three doses (50, 100, or 300 mg) of canagliflozin.

Their mean body mass index (BMI) at baseline was 37 kg/m² and 93% fell into the obese category.

The authors found that the drug did indeed do its job, significantly increasing urinary glucose excretion in a dose-dependent manner compared with placebo.

And they found that the drug achieved its primary endpoint of producing statistically significant reductions in body weight from baseline compared with placebo (P<0.05 for all):

• Placebo: -1.3%
• 50 mg: -2.2%
• 100 mg: -2.9%
• 300 mg: -2.7%

Significantly more patients on the 300-mg dose of the drug lost at least 5% of their body weight compared with placebo (19% versus 17%, P=0.027) but few subjects overall achieved greater than 10% weight loss.

Bays and colleagues also reported "small but significant" reductions in BMI for patients on the drug compared with placebo.

However, there were no clinically meaningful changes from baseline in triglycerides or high-density lipoprotein (HDL) cholesterol with canagliflozin, and there were actually increases in low-density lipoprotein (LDL) cholesterol (4.2% to 10% for the drug, compared with 6.4% on placebo).

Overall adverse event rates were similar across groups, but canagliflozin was associated with higher rates of genital mycotic infections in women. These, however, were generally mild and led to few study discontinuations, they reported.

Adverse events related to osmotic diuresis were also low and similar across groups, Bays and colleagues added.

Their study was limited by a 25% discontinuation rate, and by its short duration. Also, it was not clear how the weight loss might affect adipocyte and adipose tissue function, which would translate into long-term benefits.

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