3 Weighty Questions About Obesity and Diabetes

July 21, 2015

Questions you were afraid to ask about weight-loss modalities in the context of obesity and type 2 diabetes are answered here.

Obesity has become an unforgiving epidemic and the tip of a morbidity-mortality iceberg. This chronic disease leads to obstructive sleep apnea; type 2 diabetes, which recently tripled in prevalence1; hypertension; insulin resistance; and a host of vascular complications.

As the prevalence of obesity rises, what tools do we have in the battle against excessive weight? Remember, a weight loss of only 5% to 10% has been demonstrated to reduce complications.1

Let’s ask some key questions about weight-loss modalities in the context of obesity and type 2 diabetes:

 

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1. Where do we stand with lifestyle interventions and diet?

Some recently published papers tell us of the ongoing futility of lifestyle and dietary interventions.2 When lifestyle intervention was compared with Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding, respectively, partial or complete type 2 diabetes remission was achieved by 0%, 40%, and 29% of persons in the trial.

Another trial (the Swedish Obesity Study) compared 1658 obese persons who underwent bariatric surgery (none had diabetes) and 1771 obese matched controls who did not have surgery (also without diabetes).3 After 15 years, diabetes developed in 6.8 cases/1000 person years and 28.4 cases/1000 person years, respectively, in the surgery vs the placebo groups.3 Finally, adolescents with recent onset type 2 diabetes did not benefit from intensive lifestyle interventions.4

 

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2. Have pharmaceutical interventions fared any better in the weight loss arena?

Until very recently, the answer would have been a resounding no. But a July 2015 publication has the potential to change our thinking.1,5

Liraglutide (a GLP-1 agonist) in a dose of 3.0 mg daily s.c. was given for 56 weeks to 2487 obese persons without diabetes and compared with placebo in 1244 similar persons (mean BMI for the 2 groups was 38.3). Both groups were also instructed in lifestyle interventions. At week 56, the liraglutide group lost an average of 8.4 kg body weight and the control group 2.8 kg, and a total of 63.2% in the active limb lost at least 5% of their body weight compared with 27.1% in the placebo group.

 

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3. Where do we go from here?

The enthusiasm for liraglutide has to be tempered with further investigations. Although there were no calcitonin increases and no thyroid C-cell carcinoma in the liraglutide group, there were only modest improvements in secondary end points like glycemic control and cardiometabolic markers. Most of the obese patients randomized to liraglutide stayed obese.

But there are lingering issues with bariatric surgery as a treatment of choice. As one author put it bluntly, surgery for 400 million obese persons in the world is not a choice.5 Hopefully, the GLP-1 path will be fruitful.

 

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Take-aways:

• Lifestyle and dietary interventions for obesity and diabetes have not been as effective as bariatric surgery.

• Liraglutide, a GLP-1 agonist, may be effective in achieving weight loss.

• There are lingering issues with bariatric surgery as a treatment of choice.

References:

1. Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of Liraglutide in weight management. N Engl J Med. 2015;373:11-22.

2. Courcoulas AP, Belle SH, Neiberg RH, et al. Three-year outcomes of bariatric surgery vs lifestyle intervention for type 2 diabetes mellitus treatment: a randomized clinical trial. JAMA Surg. 2015; Jul 1. doi: 10.1001/jamasurg.2015.1534. [Epub ahead of print]

3. Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012;367:695-704.

4. Gagner M. Bariatric surgery vs. lifestyle intervention for type 2 diabetes mellitus. JAMA. 2015; Jul 1. doi: 10.1001/jamasurg.2015.1542. [Epub ahead of print]

5. Siraj ES, Williams KJ. Another agent for obesity-will this time be different? N Engl J Med. 2015;373:82-83.