Brace Yourself for the Deluge Seeking Obesity Drugs

The Food and Drug Administration’s recent approval of lorcaserin (Belviq) for the treatment of obesity is going to have an inevitable – and unavoidable – impact on our practices. You may have already talked yourself into not prescribing it, or you may practice the “5-year rule,” deciding not to prescribe a medication until it has been on the market for at least 5 years.

Either way, now is the time to develop your clinical stump speech because once the company starts its direct-to-consumer advertising campaign, your patients are going to ask you about it when you start counseling them about their weight.

So what is lorcaserin and how good are the data to support its use?
Lorcaserin is a “super selective” serotonin receptor agonist working predominantly at the 5-HT2C receptor. The theoretical mechanism of action is through an enhancement of satiety, an “anorectic effect.”

The safety and efficacy of lorcaserin has been evaluated in three phase III studies: BLOSSOM (Behavioral Modification and Lorcaserin Second Study for Obesity Management), BLOOM (Behavioral Modification and Lorcaserin for Overweight and Obesity Management), and BLOOM-DM (Diabetes Management).

The BLOSSOM trial randomized 4,008 adults aged 18-65 years with a body mass index of 30-45 kg/m2 or with a body mass index of 27-29.9 kg/m2 and a comorbid, obesity-related condition. Participants received lorcaserin 10 mg twice daily, 10 mg once daily, or placebo for 52 weeks. All patients received physical activity counseling to exercise moderately for 30 minutes per day and dietary counseling that included a reduction of 600 kcal below estimated energy requirements (JCEM 2011;96:3067-77).

At one year, lorcaserin was associated with a significantly higher proportion of patients losing at least 5% baseline body weight (47% on 10 mg b.i.d. and 40% on 10 mg once daily) compared to placebo (25%; P < .001 verses lorcaserin b.i.d.).

Weight loss of at least 10% of baseline body weight was achieved by 23% and 17% in the lorcaserin 10 mg b.i.d. and 10 mg once daily groups, respectively, compared with about 10% of those in the placebo group (P < .001 vs. lorcaserin b.i.d.). Lorcaserin b.i.d. was associated with significantly greater weight loss than once daily dosing (P < .01).

The most common side effects were headache, nausea, and dizziness. Valvulopathy was observed in 2% of the placebo and lorcaserin b.i.d. groups each. Patients taking lorcaserin lost an average of 5.8 kgs at 52 weeks.

Recall that fenfluramine (the “fen” in “fen-phen”) was a serotonergic agent that caused cardiac valvulopathy and was withdrawn from the market. But fenfluramine was a potent agonist of the serotonin 5-HT2B receptor, which are plentiful in cardiac valves. By contrast, lorcaserin binds strongly to 5-HT2C at a ratio of 100:1 to other receptors. No increased risk of valvulopathy has been observed with lorcaserin.

Another 4 to 6 months will pass before this drug comes to market. Being the first obesity drug to be approved in 13 years, pent-up demand combined with a likely aggressive advertising campaign will result in a deluge of patient inquiries.

Keep in mind that the FDA recommended restrictions on the drug by limiting approval to patients with a BMI greater than 30 kg/m2 or a BMI greater than 27 kg/m2 with other medical co-morbidities related to obesity.

Whatever we decide to do, patients need to be reminded that lifestyle change including diet and exercise remain the cornerstone of any successful weight-loss attempt and for the maintenance of those results.

Dr. Jon O. Ebbert is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He declares having no conflicts of interest. The opinions expressed are solely those of the author. Contact him at [email protected].

The Food and Drug Administration’s recent approval of lorcaserin (Belviq) for the treatment of obesity is going to have an inevitable – and unavoidable – impact on our practices. You may have already talked yourself into not prescribing it, or you may practice the “5-year rule,” deciding not to prescribe a medication until it has been on the market for at least 5 years.

Either way, now is the time to develop your clinical stump speech because once the company starts its direct-to-consumer advertising campaign, your patients are going to ask you about it when you start counseling them about their weight.

So what is lorcaserin and how good are the data to support its use?
Lorcaserin is a “super selective” serotonin receptor agonist working predominantly at the 5-HT2C receptor. The theoretical mechanism of action is through an enhancement of satiety, an “anorectic effect.”

The safety and efficacy of lorcaserin has been evaluated in three phase III studies: BLOSSOM (Behavioral Modification and Lorcaserin Second Study for Obesity Management), BLOOM (Behavioral Modification and Lorcaserin for Overweight and Obesity Management), and BLOOM-DM (Diabetes Management).

The BLOSSOM trial randomized 4,008 adults aged 18-65 years with a body mass index of 30-45 kg/m2 or with a body mass index of 27-29.9 kg/m2 and a comorbid, obesity-related condition. Participants received lorcaserin 10 mg twice daily, 10 mg once daily, or placebo for 52 weeks. All patients received physical activity counseling to exercise moderately for 30 minutes per day and dietary counseling that included a reduction of 600 kcal below estimated energy requirements (JCEM 2011;96:3067-77).

At one year, lorcaserin was associated with a significantly higher proportion of patients losing at least 5% baseline body weight (47% on 10 mg b.i.d. and 40% on 10 mg once daily) compared to placebo (25%; P < .001 verses lorcaserin b.i.d.).

Weight loss of at least 10% of baseline body weight was achieved by 23% and 17% in the lorcaserin 10 mg b.i.d. and 10 mg once daily groups, respectively, compared with about 10% of those in the placebo group (P < .001 vs. lorcaserin b.i.d.). Lorcaserin b.i.d. was associated with significantly greater weight loss than once daily dosing (P < .01).

The most common side effects were headache, nausea, and dizziness. Valvulopathy was observed in 2% of the placebo and lorcaserin b.i.d. groups each. Patients taking lorcaserin lost an average of 5.8 kgs at 52 weeks.

Recall that fenfluramine (the “fen” in “fen-phen”) was a serotonergic agent that caused cardiac valvulopathy and was withdrawn from the market. But fenfluramine was a potent agonist of the serotonin 5-HT2B receptor, which are plentiful in cardiac valves. By contrast, lorcaserin binds strongly to 5-HT2C at a ratio of 100:1 to other receptors. No increased risk of valvulopathy has been observed with lorcaserin.

Another 4 to 6 months will pass before this drug comes to market. Being the first obesity drug to be approved in 13 years, pent-up demand combined with a likely aggressive advertising campaign will result in a deluge of patient inquiries.

Keep in mind that the FDA recommended restrictions on the drug by limiting approval to patients with a BMI greater than 30 kg/m2 or a BMI greater than 27 kg/m2 with other medical co-morbidities related to obesity.

Whatever we decide to do, patients need to be reminded that lifestyle change including diet and exercise remain the cornerstone of any successful weight-loss attempt and for the maintenance of those results.

Dr. Jon O. Ebbert is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He declares having no conflicts of interest. The opinions expressed are solely those of the author. Contact him at [email protected].

The Food and Drug Administration’s recent approval of lorcaserin (Belviq) for the treatment of obesity is going to have an inevitable – and unavoidable – impact on our practices. You may have already talked yourself into not prescribing it, or you may practice the “5-year rule,” deciding not to prescribe a medication until it has been on the market for at least 5 years.

Either way, now is the time to develop your clinical stump speech because once the company starts its direct-to-consumer advertising campaign, your patients are going to ask you about it when you start counseling them about their weight.

So what is lorcaserin and how good are the data to support its use?
Lorcaserin is a “super selective” serotonin receptor agonist working predominantly at the 5-HT2C receptor. The theoretical mechanism of action is through an enhancement of satiety, an “anorectic effect.”

The safety and efficacy of lorcaserin has been evaluated in three phase III studies: BLOSSOM (Behavioral Modification and Lorcaserin Second Study for Obesity Management), BLOOM (Behavioral Modification and Lorcaserin for Overweight and Obesity Management), and BLOOM-DM (Diabetes Management).

The BLOSSOM trial randomized 4,008 adults aged 18-65 years with a body mass index of 30-45 kg/m2 or with a body mass index of 27-29.9 kg/m2 and a comorbid, obesity-related condition. Participants received lorcaserin 10 mg twice daily, 10 mg once daily, or placebo for 52 weeks. All patients received physical activity counseling to exercise moderately for 30 minutes per day and dietary counseling that included a reduction of 600 kcal below estimated energy requirements (JCEM 2011;96:3067-77).

At one year, lorcaserin was associated with a significantly higher proportion of patients losing at least 5% baseline body weight (47% on 10 mg b.i.d. and 40% on 10 mg once daily) compared to placebo (25%; P < .001 verses lorcaserin b.i.d.).

Weight loss of at least 10% of baseline body weight was achieved by 23% and 17% in the lorcaserin 10 mg b.i.d. and 10 mg once daily groups, respectively, compared with about 10% of those in the placebo group (P < .001 vs. lorcaserin b.i.d.). Lorcaserin b.i.d. was associated with significantly greater weight loss than once daily dosing (P < .01).

The most common side effects were headache, nausea, and dizziness. Valvulopathy was observed in 2% of the placebo and lorcaserin b.i.d. groups each. Patients taking lorcaserin lost an average of 5.8 kgs at 52 weeks.

Recall that fenfluramine (the “fen” in “fen-phen”) was a serotonergic agent that caused cardiac valvulopathy and was withdrawn from the market. But fenfluramine was a potent agonist of the serotonin 5-HT2B receptor, which are plentiful in cardiac valves. By contrast, lorcaserin binds strongly to 5-HT2C at a ratio of 100:1 to other receptors. No increased risk of valvulopathy has been observed with lorcaserin.

Another 4 to 6 months will pass before this drug comes to market. Being the first obesity drug to be approved in 13 years, pent-up demand combined with a likely aggressive advertising campaign will result in a deluge of patient inquiries.

Keep in mind that the FDA recommended restrictions on the drug by limiting approval to patients with a BMI greater than 30 kg/m2 or a BMI greater than 27 kg/m2 with other medical co-morbidities related to obesity.

Whatever we decide to do, patients need to be reminded that lifestyle change including diet and exercise remain the cornerstone of any successful weight-loss attempt and for the maintenance of those results.

Dr. Jon O. Ebbert is a professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He declares having no conflicts of interest. The opinions expressed are solely those of the author. Contact him at [email protected].