New research providing further support for obesity drugs

December 18, 2023

Tirzepetide weight regain after discontinuation

Source: Arrone, JAMA December 11, 2023 LINK

There were three research publications on the anti-obesity GLP-1 drugs of interest to employers this last week.

a)    Those who stop tirzepatide regain some but not all of the weight they lost
Research published in JAMA (graphic above) showed that people lose an average of 20% of their body weight on tirzepatide (Zepbound) for 36 weeks, and those who remain on the drug continue to lose weight over the following 52 weeks. Those who are switched to placebo after the first 36 weeks regained more than half of the weight they lost - but they continue to have weight that is 9.5% less than their initial weight a year after discontinuation of active medication. This is very similar to weight regain after discontinuation with semaglutide (Wegovy) published last month.

b)    GLP-1s as safe in pregnancy as insulin
Research published in JAMA Internal Medicine showed that women who developed diabetes in pregnancy and were treated with GLP-1 medications had no worse outcomes than those who were treated with insulin. These drugs are generally not recommended for weight loss in pregnancy for fear that they will lead to women not eating enough calories. But this study provides reassurance around safety in pregnancy.

c)     GLP-1s associated with lower rate of colorectal cancer in diabetics
Research published in JAMA Oncology showed that diabetics treated with GLP-1 medications had lower rates of colorectal cancer over 15 years of follow-up compared to a matched group of diabetics treated with other medications. The study looked at de-identified medical records of over 100 million patients, of whom 1.2 million who had initial diabetic drug prescriptions during the study period. They found that GLP-1 drugs were associated with 46% fewer diagnoses of colorectal cancer compared to treatment with insulin. The GLP-1 drugs were associated with lower rates of colorectal cancer even in those who were not obese.

Implications for employers:

-        Weight gain after discontinuation of GLP-1 medications is a challenge to plans seeking to implement lifetime limits. Some vendors propose that a lifestyle management program will help people maintain weight loss after discontinuation of GLP-1 drugs, but I have not seen any published research supporting this.

-        Published data on safety in pregnancy argues against coverage edits that would exclude this class of drugs for pregnant women.

-        Long-term apparent decrease in colorectal cancer risk in diabetics is reassuring, and given association of obesity with higher rates of colorectal cancer, we are likely to see this in people treated with GLP-1s for obesity, too.

Addendum: New England Journal published an article on Thursday showing a 20% decrease in major cardiovascular events in nondiabetics with BMI>=27 on semaglutide compared to placebo. This article first appeared online last month. One in six in the semaglutide group stopped due to drug side effects, compared to 1 in 12 of those assigned to placebo. At the end of four years, cardiovascular and all cause deaths and heart failure rates were lower in the group treated with semaglutide, too.

Source: Lincoff, et al NEJM 12/14/23 LINK

Tomorrow: FDA approves two new therapies for sickle cell disease

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