Drug Helps Both Patients with and without Diabetes Lose Weight

Tina Vilsboll, MD, of the University of Copenhagen, in Denmark, and colleagues reported In BMJ, a review and meta-analysis, all patients taking GLP-1 agonists, whether they had diabetes or not, achieved greater weight loss -- about 6.4 lbs more -- than controls on placebo or other diabetes drugs.

"Our results suggest that treatment with GLP-1 agonists is an effective intervention for participants who are overweight, irrespective of whether they have diabetes," they wrote.

Raj Padwal, MD, of Mackenzie Health Sciences Center in Edmonton, Canada, wrote in an accompanying editorial, that the drugs shouldn't be used for this indication, especially not in nondiabetic patients, until further research is done, particularly on potential cardiovascular risks.

It's known that weight loss isn't easily accomplished or maintained, as many nonpharmacologic strategies have proven ineffective. At the same time, pharmaceutical options have been withdrawn from the market for various risks and side effects, and several newer agents such as Contrave, Qnexa, and Lorqess have failed to show sufficient efficacy or lack of harm to win FDA approval.

Although many diabetes drugs such as sulfonylureas and insulin are associated with weight gain, GLP-1 agonists help patients lose weight, largely due to their ability to suppress appetite. Researchers have long been interested in whether or not this strategy can be effective in nondiabetic patients as well.

So Vilsboll and colleagues conducted a review and meta-analysis of randomized controlled trials of overweight or obese patients with or without type 2 diabetes who were on exenatide (Byetta) twice daily or once weekly or daily liraglutide (Victoza) for at least 20 weeks.

They included 25 trials conducted between January 2004 and May 2011 totaling 6,411 patients. Controls received either placebo, oral anti-diabetic drugs, or insulin.

The researchers found that patients on GLP-1 agonists lost more weight than controls (mean difference -2.9 kg [-6.4 lbs]), and subgroup analyses showed greater weight loss for those on the highest doses of the drugs, they reported.

Both diabetics and nondiabetics on GLP-1 agonists had better weight loss than controls, they found (mean -2.8 kg [-6.2 lbs] and -3.2 kg [7 lbs], respectively). The results were similar for liraglutide and exenatide at various doses.

The drugs also had better effects on systolic and diastolic blood pressure, plasma cholesterol, and glycemic control, though there were no differences in effect on plasma liver enzymes. This suggests GLP-1 agonists may not have any impact on the prevention of nonalcoholic fatty liver disease, for which obese and diabetic patients are at high risk, they said.

Vilsboll and colleagues cautioned that the agents were, however, associated with nausea, diarrhea, and vomiting, and further research on comorbidities such as cardiovascular diseases still needs to be done before any recommendations can be made.

Regression analyses didn't show any evidence of bias or small-study effects, but the review was limited by the limitations of the included studies.

In the editorial, Padwal warned about several other caveats in the study: body weight was a secondary, not primary, endpoint in most of the trials; the findings combine the results of trials using placebo and active comparator arms; and the estimates were associated with substantial heterogeneity.

He noted that, in the subgroup analysis of 10 placebo-controlled trials, GLP-1 agonists reduced weight by 1.9 kg (4.2 lbs.), which is likely "a more accurate estimate of the weight reductions that would be expected in clinical practice."

And aside from unstudied cardiovascular risks, Padwal also cautioned about the potential risks of pancreatitis, pancreatic cancer, and thyroid C-cell tumors that have been raised with this class of agents.

He concluded that the findings shouldn't yet change clinical practice, and "off-label use of GLP-1 agonists for weight loss in people without diabetes cannot be recommended at this time."

• This meta-analysis found that one class of diabetes drugs -- the glucagon-like peptide-1 receptor (GLP-1) agonists -- can help diabetics and nondiabetics alike lose weight.
• The drugs shouldn't be used for this indication, especially not in nondiabetic patients, until further research is done, particularly on potential cardiovascular risks.

Vilsboll T, et al "Effects of glucagon-like peptide-1 receptor agonists on weight loss: Systematic review and meta-analysis of randomized controlled trials" BMJ 2012; DOI:10.1136/bmj.d7771.